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Sample records for open-label multicenter phase

  1. Efficacy and safety of long-acting pasireotide in Japanese patients with acromegaly or pituitary gigantism: results from a multicenter, open-label, randomized, phase 2 study.

    Science.gov (United States)

    Tahara, Shigeyuki; Murakami, Mami; Kaneko, Tomomi; Shimatsu, Akira

    2017-07-28

    A multicenter, open-label, phase 2 study was conducted to investigate the efficacy and safety of long-acting pasireotide formulation in Japanese patients with acromegaly or pituitary gigantism. Medically naïve or inadequately controlled patients (on somatostatin analogues or dopamine agonists) were included. Primary end point was the proportion of all patients who achieved biochemical control (mean growth hormone [GH] levelsacromegaly, n=32; pituitary gigantism, n=1) were enrolled and randomized 1:1:1 to receive open-label pasireotide 20mg, 40mg, or 60mg. The median age was 52 years (range, 31-79) and 20 patients were males. At month 3, 18.2% of patients (6/33; 90% confidence interval: 8.2%, 32.8%) had biochemical control (21.2% [7/33] when including a patient with mean GHacromegaly or pituitary gigantism.

  2. Pharmacokinetics, pharmacodynamics, and safety of pasireotide LAR in patients with acromegaly: a randomized, multicenter, open-label, phase I study.

    Science.gov (United States)

    Petersenn, Stephan; Bollerslev, Jens; Arafat, Ayman M; Schopohl, Jochen; Serri, Omar; Katznelson, Laurence; Lasher, Janet; Hughes, Gareth; Hu, Ke; Shen, George; Reséndiz, Karina Hermosillo; Giannone, Vanessa; Beckers, Albert

    2014-11-01

    Pasireotide (SOM230), a multireceptor-targeted somatostatin analogue, has exhibited favorable safety/tolerability in several clinical studies. A long-acting-release (LAR) formulation of pasireotide may offer advantages over the subcutaneous formulation. This randomized, open-label, Phase I study evaluated the safety, PK, and PD of pasireotide LAR 20, 40, or 60 mg/month in patients with acromegaly. Safety assessments and blood samples for PK and PD were taken at designated time points. Thirty-five patients were randomized and completed the study. Steady-state pasireotide concentrations were achieved following three monthly injections. Trough pasireotide concentrations (ng/mL) 28 days after each injection were: 2.48, 4.16, and 3.10 (20 mg group); 6.42, 6.62, and 7.12 (40 mg group); and 9.51, 11.7, and 13.0 (60 mg group). At study end, 51% and 57% of patients achieved GH levels ≤2.5 μg/L and IGF-1 levels below ULN, respectively. Compared with baseline, fasting blood glucose and HbA1c levels increased, whereas fasting blood insulin levels decreased. Acromegaly symptoms were generally improved. Adverse events were mostly gastrointestinal and mild/moderate. Pasireotide LAR was generally well tolerated. Steady-state PK was achieved after three monthly doses; exposures were approximately dose proportional. Control of GH, IGF-1, and symptoms improved, suggesting that pasireotide LAR may be an effective treatment for acromegaly.

  3. A Phase Ib Open-Label Multicenter Study of AZD4547 in Patients with Advanced Squamous Cell Lung Cancers.

    Science.gov (United States)

    Paik, Paul K; Shen, Ronglai; Berger, Michael F; Ferry, David; Soria, Jean-Charles; Mathewson, Alastair; Rooney, Claire; Smith, Neil R; Cullberg, Marie; Kilgour, Elaine; Landers, Donal; Frewer, Paul; Brooks, Nigel; André, Fabrice

    2017-09-15

    Purpose: Squamous cell lung cancers (SQCLC) account for 25% of all NSCLCs, yet the prognosis of these patients is poor and treatment options are limited. Amplified FGFR1 is one of the most common oncogenic events in SQCLCs, occurring in approximately 20% of cases. AZD4547 is a potent and selective FGFR1-3 inhibitor with antitumor activity in FGFR1-amplified SQCLC cell lines and patient-derived xenografts.Experimental Design: On the basis of these data, we performed a phase I study of AZD4547 in patients with previously treated stage IV FGFR1-amplified SQCLCs (NCT00979134). FGFR1 amplification (FGFR1:CEP8 ≥ 2) was determined by FISH. The primary endpoint was safety/tolerability. Secondary endpoints included antitumor activity, pharmacokinetics, pharmacodynamics, and molecular analyses.Results: Fifteen FGFR1-amplified patients were treated. The most common related adverse events (AE) were gastrointestinal and dermatologic. Grade ≥3-related AEs occurred in 3 patients (23%). Thirteen patients were evaluable for radiographic response assessment. The overall response rate was 8% (1 PR). Two of 15 patients (13.3%) were progression-free at 12 weeks, and the median overall survival was 4.9 months. Molecular tests, including next-generation sequencing, gene expression analysis, and FGFR1 immunohistochemistry, showed poor correlation between gene amplification and expression, potential genomic modifiers of efficacy, and heterogeneity in 8p11 amplicon.Conclusions: AZD4547 was tolerable at a dosage of 80 mg oral twice a day, with modest antitumor activity. Detailed molecular studies show that these tumors are heterogeneous, with a range of mutational covariates and stark differences in gene expression of the 8p11 amplicon that likely explain the modest efficacy of FGFR inhibition in this disease. Clin Cancer Res; 23(18); 5366-73. ©2017 AACR. ©2017 American Association for Cancer Research.

  4. Nimotuzumab plus chemotherapy versus chemotherapy alone in advanced non-small-cell lung cancer: a multicenter, randomized, open-label Phase II study

    Directory of Open Access Journals (Sweden)

    Babu KG

    2014-06-01

    Full Text Available K Govind Babu,1 Kumar Prabhash,2 Ashok K Vaid,3 Bhawna Sirohi,3 Ravi B Diwakar,4 Raghunadha Rao,5 Madhuchanda Kar,6 Hemant Malhotra,7 Shona Nag,8 Chanchal Goswami,9 Vinod Raina,10 Ravi Mohan111Kidwai Memorial Institute of Oncology, Bangalore, 2Tata Memorial Hospital, Mumbai, 3Artemis Health Institute, Delhi, 4Bangalore Institute of Oncology, Bangalore, 5Nizam Institute of Medical Sciences, Hyderabad, 6B R Singh Hospital, Kolkata, 7Birla Cancer Centre, Jaipur, 8Jehangir Hospital, Pune, 9B P Poddar Hospital and Medical Research Ltd, Kolkata, 10Institute Rotary Cancer Hospital, New Delhi, 11King George Hospital, Visakhapatnam, IndiaBackground: The purpose of this study was to evaluate the safety and efficacy of nimotuzumab in combination with chemotherapy (docetaxel and carboplatin versus chemotherapy alone in patients with stage IIIB/IV non-small-cell lung cancer.Methods: This multicenter, open-label, Phase II study randomized 110 patients to receive nimotuzumab plus chemotherapy (nimotuzumab group or chemotherapy alone (control group, and comprised concomitant, maintenance, and follow-up phases. Nimotuzumab 200 mg was administered once weekly for 13 weeks during the first two phases with four cycles of chemotherapy and docetaxel 75 mg/m2 and carboplatin (area under the curve 5 mg/mL*min every 3 weeks for a maximum of four cycles during the concomitant phase. The primary endpoint was objective response rate (sum of complete response and partial response. Secondary endpoints, ie, overall survival and progression-free survival, were estimated using the Kaplan–Meier method. Efficacy was evaluated on the intent-to-treat and efficacy-evaluable sets. Safety was assessed from adverse event and serious adverse event data.Results: The objective response rate was significantly higher in the nimotuzumab group than in the control group in the intent-to-treat population (54% versus 34.5%; P=0.04. A complete response and partial response were achieved in 3

  5. An Open-Label, Multicenter, Randomized, Phase II Study of Pazopanib in Combination with Pemetrexed in First-Line Treatment of Patients with Advanced-Stage Non-Small-Cell Lung Cancer

    DEFF Research Database (Denmark)

    Scagliotti, Giorgio V; Felip, Enriqueta; Besse, Benjamin;

    2013-01-01

    This randomized open-label phase II study evaluated the efficacy, safety, and tolerability of pazopanib in combination with pemetrexed compared with the standard cisplatin/pemetrexed doublet in patients with previously untreated, advanced, nonsquamous non-small-cell lung cancer.......This randomized open-label phase II study evaluated the efficacy, safety, and tolerability of pazopanib in combination with pemetrexed compared with the standard cisplatin/pemetrexed doublet in patients with previously untreated, advanced, nonsquamous non-small-cell lung cancer....

  6. A Multicenter, Open-Label, Phase 1b Study of Carfilzomib, Cyclophosphamide, and Dexamethasone in Newly Diagnosed Multiple Myeloma Patients (CHAMPION-2).

    Science.gov (United States)

    Boccia, Ralph V; Bessudo, Alberto; Agajanian, Richy; Conkling, Paul; Harb, Wael; Yang, Hui; Pinchasik, Dawn; Kimball, Amy S; Berenson, James R

    2017-07-01

    This phase 1b study evaluated the safety and efficacy of 3 dose levels of carfilzomib when provided with fixed dose oral cyclophosphamide and dexamethasone (KCyd) in patients with newly diagnosed multiple myeloma (MM). CHAMPION-2 was a multicenter single-arm study. Patients with newly diagnosed secretory MM were enrolled and received KCyd treatment for up to 8 cycles. A 3 + 3 dose escalation scheme was used to evaluate twice-weekly carfilzomib at 36, 45, and 56 mg/m(2) dose levels, followed by a dose expansion. No dose-limiting toxicities were observed in any of the dose evaluation cohorts. The KCyd regimen that included the maximum planned carfilzomib dose of 56 mg/m(2) twice weekly was brought forward into dose expansion. A total of 16 patients were treated at this dose level. At 56 mg/m(2) the overall response rate was 87.5% (95% confidence interval, 61.7-98.4), and the median time to response of 14 patients whose disease responded to therapy was 1 month. At this dose level, common adverse events of grade 3 or higher were anemia (25.0%), neutropenia (18.8%), acute kidney injury (12.5%), and decreased white blood cell count (12.5%). Ten of 16 patients who received carfilzomib at 56 mg/m(2) completed all 8 cycles, 5 patients discontinued study therapy before cycle 8 as a result of adverse events, and 1 patient discontinued therapy as a result of progressive disease. Carfilzomib in combination with cyclophosphamide and dexamethasone is effective and has manageable toxicity for patients with newly diagnosed MM. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Gd-EOB-DTPA-enhanced magnetic resonance imaging for focal liver lesions in Chinese patients:a multicenter, open-label, phase III study

    Institute of Scientific and Technical Information of China (English)

    Meng-Su Zeng; Hui-Yi Ye; Liang Guo; Wei-Jun Peng; Jian-Ping Lu; Gao-Jun Teng; Yi Huan; Ping Li; Jian-Rong Xu

    2013-01-01

    BACKGROUND: Contrast agents help to improve visibility in magnetic resonance (MR) imaging. However, owing to the large interstitial spaces of the liver, there is a reduction in the natural contrast gradient between lesions and healthy tissue. This study was undertaken to evaluate the efficacy and safety of the liver-specific MR imaging contrast agent gadoxetate disodium (Gd-EOB-DTPA) in Chinese patients. METHODS: This  was  a  single-arm,  open-label,  multicenter study  in  patients  with  known  or  suspected  focal  liver  lesions referred for contrast-enhanced MR imaging. MR imaging was performed in 234 patients before and after a single intravenous bolus of Gd-EOB-DTPA (0.025 mmol/kg body weight). Images were  evaluated  by  clinical  study  investigators  and  three independent,  blinded  radiologists.  The  primary  efficacy endpoint was sensitivity in lesion detection. RESULTS: Gd-EOB-DTPA  improved  sensitivity  in  lesion detection  by  9.46%  compared  with  pre-contrast  imaging  for the average of the three blinded readers (94.78% vs 85.32% for Gd-EOB-DTPA  vs  pre-contrast,  respectively).  Improvements in  detection  were  more  pronounced  in  lesions  less  than  1 cm.  Gd-EOB-DTPA  improved  diagnostic  accuracy  in  lesion classification. CONCLUSIONS: This  open-label  study  demonstrated  that Gd-EOB-DTPA improves diagnostic sensitivity in liver lesions, particularly  in  those  smaller  than  1  cm.  Gd-EOB-DTPA  also significantly  improves  the  diagnostic  accuracy  in  lesion classification,  and  furthermore,  Gd-EOB-DTPA  is  safe  in Chinese patients with liver lesions.

  8. A Phase 3, multicenter, open-label, switchover trial to assess the safety and efficacy of taliglucerase alfa, a plant cell-expressed recombinant human glucocerebrosidase, in adult and pediatric patients with Gaucher disease previously treated with imiglucerase.

    Science.gov (United States)

    Pastores, Gregory M; Petakov, Milan; Giraldo, Pilar; Rosenbaum, Hanna; Szer, Jeffrey; Deegan, Patrick B; Amato, Dominick J; Mengel, Eugen; Tan, Ee Shien; Chertkoff, Raul; Brill-Almon, Einat; Zimran, Ari

    2014-12-01

    Taliglucerase alfa is a β-glucosidase enzyme replacement therapy (ERT) approved in the US and other countries for the treatment of Gaucher disease (GD) in adults and is approved in pediatric and adult patients in Australia and Canada. It is the first approved plant cell-expressed recombinant human protein. A Phase 3, multicenter, open-label, 9-month study assessed safety and efficacy of switching to taliglucerase alfa in adult and pediatric patients with GD treated with imiglucerase for at least the previous 2years. Patients with stable disease were offered taliglucerase alfa treatment using the same dose (9-60U/kg body weight) and regimen of administration (every 2weeks) as imiglucerase. This report summarizes results from 26 adult and 5 pediatric patients who participated in the trial. Disease parameters (spleen and liver volumes, hemoglobin concentration, platelet count, and biomarker levels) remained stable through 9months of treatment in adults and children following the switch from imiglucerase. All treatment-related adverse events were mild or moderate in severity and transient in nature. Exploratory parameters of linear growth and development showed positive outcomes in pediatric patients. These findings provide evidence of the efficacy and safety profile of taliglucerase alfa as an ERT for GD in patients previously treated with imiglucerase. This trial was registered at www.clinicaltrials.gov as # NCT00712348.

  9. Phase III, multicenter, open-label, long-term study of the safety of abatacept in Japanese patients with rheumatoid arthritis and an inadequate response to conventional or biologic disease-modifying antirheumatic drugs

    OpenAIRE

    Takeuchi, Tsutomu; Matsubara, Tsukasa; Urata, Yukitomo; Suematsu, Eiichi; Ohta, Shuji; Honjo, Shigeru; Abe, Tohru; Yamamoto, Ami; Miyasaka, Nobuyuki; ,

    2014-01-01

    Objectives To examine the long-term safety of intravenous (IV) abatacept treatment in Japanese patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) or other conventional or biologic disease-modifying antirheumatic drugs. Methods This Phase III, open-label, long-term study (NCT00484289) comprised Japanese patients with RA who had completed abatacept Phase I or Phase II studies, and new patients intolerant to MTX. Patients from Phase I and Phase II studies re...

  10. A Phase IIb, Multicenter, Open-Label, Safety, and Efficacy Study of High-Dose, Propylene Glycol-Free Melphalan Hydrochloride for Injection (EVOMELA) for Myeloablative Conditioning in Multiple Myeloma Patients Undergoing Autologous Transplantation.

    Science.gov (United States)

    Hari, Parameswaran; Aljitawi, Omar S; Arce-Lara, Carlos; Nath, Rajneesh; Callander, Natalie; Bhat, Gajanan; Allen, Lee F; Stockerl-Goldstein, Keith

    2015-12-01

    Autologous stem cell transplantation (ASCT) after high-dose melphalan conditioning is considered a standard of care procedure for patients with multiple myeloma (MM). Current formulations of melphalan (eg, Alkeran for Injection [melphalan hydrochloride]; GlaxoSmithKline, Research Triangle Park, NC, USA) have marginal solubility and limited chemical stability upon reconstitution. Alkeran requires the use of propylene glycol as a co-solvent, which itself has been reported to cause such complications as metabolic/renal dysfunction and arrhythmias. EVOMELA (propylene glycol-free melphalan HCl; Spectrum Pharmaceuticals, Inc., Irvine, CA, USA) is a new i.v. melphalan formulation that incorporates Captisol (Ligand Pharmaceuticals, Inc., La Jolla, CA, USA), a specially modified cyclodextrin that improves the solubility and stability of melphalan and eliminates the need for propylene glycol. This new formulation has been shown to be bioequivalent to Alkeran. EVOMELA (200 mg/m(2)) was administered as 2 doses of 100 mg/m(2) each in a phase IIb, open-label, multicenter study to confirm its safety and efficacy as a high-dose conditioning regimen for patients with MM undergoing ASCT. At 5 centers, 61 patients (26 women) with a median age of 62 years (range, 32-73) were enrolled. All patients achieved myeloablation with a median time of 5 days post-ASCT, and all successfully achieved neutrophil and platelet engraftment with median times of 12 days post-ASCT and 13 days post-ASCT, respectively; treatment-related mortality on day 100 was 0%. Overall response rate (according to independent, blinded review) was high (100%), with an overall complete response rate of 21% (13% stringent complete response; 8% complete response) and overall partial response rate of 79% (61% very good partial response; 18% partial response). The incidence of grade 3 mucositis and stomatitis was low (10% and 5%, respectively) with no grade 4 mucositis or stomatitis reported (graded according to National

  11. Brief Report: Switching to Tenofovir Alafenamide, Coformulated With Elvitegravir, Cobicistat, and Emtricitabine, in HIV-Infected Adults With Renal Impairment: 96-Week Results From a Single-Arm, Multicenter, Open-Label Phase 3 Study.

    Science.gov (United States)

    Post, Frank A; Tebas, Pablo; Clarke, Amanda; Cotte, Laurent; Short, William R; Abram, Michael E; Jiang, Shuping; Cheng, Andrew; Das, Moupali; Fordyce, Marshall W

    2017-02-01

    Tenofovir disoproxil fumarate is associated with renal and bone toxicity. In a single-arm, open-label study of 242 virologically suppressed, HIV-infected participants with creatinine clearance 30-69 mL/min who switched to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, participants had stable creatinine clearance, significant and durable improvements in proteinuria, albuminuria, and tubular proteinuria (P < 0.001), and significant increases in hip and spine bone mineral density through 96 weeks (P < 0.001). Eighty-eight percent maintained HIV-1 RNA <50 c/mL at week 96. These longer-term results support the use of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in HIV-infected individuals with mild-moderately impaired renal function.

  12. An Open-Label, Multicenter, Phase 1/2 Study of E7438 (EZH2 Histone Methyl Transferase [HMT] Inhibitor) as a Single Agent in Subjects With Advanced Solid Tumors or With B-cell Lymphomas

    Science.gov (United States)

    2016-09-01

    B-cell Lymphomas (Phase 1); Advanced Solid Tumors (Phase 1); Diffuse Large B-cell Lymphoma (Phase 2); Follicular Lymphoma (Phase 2); Transformed Follicular Lymphoma; Primary Mediastinal Large B-Cell Lymphoma

  13. A Multicenter, Open-Label, Controlled Phase II Study to Evaluate Safety and Immunogenicity of MVA Smallpox Vaccine (IMVAMUNE in 18-40 Year Old Subjects with Diagnosed Atopic Dermatitis.

    Directory of Open Access Journals (Sweden)

    Richard N Greenberg

    Full Text Available Replicating smallpox vaccines can cause severe complications in individuals with atopic dermatitis (AD. Prior studies evaluating Modified Vaccinia Ankara virus (MVA, a non-replicating vaccine in humans, showed a favorable safety and immunogenicity profile in healthy volunteers.This Phase II study compared the safety and immunogenicity of MVA enrolling groups of 350 subjects with AD (SCORAD ≤ 30 and 282 healthy subjects.Subjects were vaccinated twice with MVA, each dose given subcutaneously 4 weeks apart. Adverse events, cardiac parameters, and the development of vaccinia virus humoral immune responses were monitored.The overall safety of the vaccine was similar in both groups. Adverse events affecting skin were experienced significantly more often in subjects with AD, but the majority of these events were mild to moderate in intensity. Seroconversion rates and geometric mean titers for total and neutralizing vaccinia-specific antibodies in the AD group were non-inferior compared to the healthy subjects.The size of the study population limited the detection of serious adverse events occurring at a frequency less than 1%.MVA has a favorable safety profile and the ability to elicit vaccinia-specific immune responses in subjects with AD.ClinicalTrials.gov NCT00316602.

  14. A Multicenter, Open-Label, Controlled Phase II Study to Evaluate Safety and Immunogenicity of MVA Smallpox Vaccine (IMVAMUNE) in 18–40 Year Old Subjects with Diagnosed Atopic Dermatitis

    Science.gov (United States)

    Greenberg, Richard N; Hurley, Yadira; Dinh, Dinh V.; Mraz, Serena; Vera, Javier Gomez; von Bredow, Dorothea; von Krempelhuber, Alfred; Roesch, Siegfried; Virgin, Garth; Arndtz-Wiedemann, Nathaly; Meyer, Thomas Peter; Schmidt, Darja; Nichols, Richard; Young, Philip; Chaplin, Paul

    2015-01-01

    Background Replicating smallpox vaccines can cause severe complications in individuals with atopic dermatitis (AD). Prior studies evaluating Modified Vaccinia Ankara virus (MVA), a non-replicating vaccine in humans, showed a favorable safety and immunogenicity profile in healthy volunteers. Objective This Phase II study compared the safety and immunogenicity of MVA enrolling groups of 350 subjects with AD (SCORAD ≤ 30) and 282 healthy subjects. Methods Subjects were vaccinated twice with MVA, each dose given subcutaneously 4 weeks apart. Adverse events, cardiac parameters, and the development of vaccinia virus humoral immune responses were monitored. Results The overall safety of the vaccine was similar in both groups. Adverse events affecting skin were experienced significantly more often in subjects with AD, but the majority of these events were mild to moderate in intensity. Seroconversion rates and geometric mean titers for total and neutralizing vaccinia-specific antibodies in the AD group were non-inferior compared to the healthy subjects. Limitations The size of the study population limited the detection of serious adverse events occurring at a frequency less than 1%. Conclusion MVA has a favorable safety profile and the ability to elicit vaccinia-specific immune responses in subjects with AD. Trial Registration ClinicalTrials.gov NCT00316602 PMID:26439129

  15. A multicenter, open-label, randomized phase II controlled study of rh-endostatin (Endostar) in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer.

    Science.gov (United States)

    Lu, Shun; Li, Lu; Luo, Yi; Zhang, Li; Wu, Gang; Chen, Zhiwei; Huang, Cheng; Guo, Shuliang; Zhang, Yiping; Song, Xiangqun; Yu, Yongfeng; Zhou, Caicun; Li, Wei; Liao, Meilin; Li, Baolan; Xu, Liyan; Chen, Ping; Hu, Chunhong; Hu, Chengping

    2015-01-01

    Based on promising efficacy in a single-arm study, a randomized phase II trial was designed to compare the efficacy and safety of adding rh-endostatin (Endostar) to first-line standard etoposide and carboplatin (EC) chemotherapy for treatment of extensive-stage small-cell lung cancer. One hundred forty Chinese patients with pathologically confirmed, extensive-stage small-cell lung cancer were randomly assigned to EC alone or rh-endostatin + EC for 4-6 cycles, followed by single-agent rh-endostatin until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival, Objective response rate (ORR), and quality of life. Median PFS was 6.4 months with rh-endostatin + EC (n = 69) and 5.9 months with EC (n = 69) (hazard ratio 0.8 [95% confidence interval 0.6-1.1]). PFS was significantly higher with rh-endostatin + EC than with EC (hazard ratio 0.4 [0.2-0.9; p = 0.020]) in female. Median overall survival was similar in both groups (12.1 versus 12.4 months, respectively [p = 0.82]). ORR was higher in the rh-endostatin + EC group (75.4%) than in the EC group (66.7%) (p = 0.348). The efficacy of rh-endostatin + EC relative to that of EC was reflected by greater improvements in patient-assessed quality of life scores after 4 and 6 weeks of treatment. There was no difference between each regimen in the incidence of nonhematological or Grade III-IV hematological toxicities. Addition of rh-endostatin to EC for the treatment of extensive-stage small-cell lung cancer had an acceptable toxicity profile, but did not improve overall survival, PFS, and ORR.

  16. Topical tretinoin 0.1% for pregnancy-related abdominal striae: an open-label, multicenter, prospective study.

    Science.gov (United States)

    Rangel, O; Arias, I; García, E; Lopez-Padilla, S

    2001-01-01

    In an open-label, multicenter, prospective study, 20 women applied tretinoin (retinoic acid) cream 0.1% daily for 3 months to pregnancy-related stretch marks in the abdominal area. Efficacy was evaluated by analysis of one preselected target lesion, which was rated on a six-point scale (-1 = worse to 4 = cleared). At week 12, significant global improvement was noted from baseline in all stretch marks, and the target lesion decreased in length by 20% (P = .01). Erythema and scaling, the most common adverse events, occurred in 11 patients, decreased in severity after the first month of treatment, and were controlled with continued application of tretinoin and petroleum jelly ointment. In this small study, topical application of tretinoin significantly improved the clinical appearance of pregnancy-related stretch marks.

  17. Adjunctive corticosteroid therapy for Pneumocystis carinii pneumonia in AIDS: a randomized European multicenter open label study

    DEFF Research Database (Denmark)

    Nielsen, T L; Eeftinck Schattenkerk, J K; Jensen, B N

    1992-01-01

    Fifty-nine human immunodeficiency virus type-1-infected patients with a microscopically proven first episode of moderate to severe Pneumocystis carinii pneumonia (PCP) were enrolled into a randomized European multicenter study. The effect of adjunctive corticosteroid (CS) therapy was assessed on (a...

  18. Blonanserin Augmentation of Atypical Antipsychotics in Patients with Schizophrenia-Who Benefits from Blonanserin Augmentation?: An Open-Label, Prospective, Multicenter Study

    National Research Council Canada - National Science Library

    Woo, Young Sup; Park, Joo Eon; Kim, Do-Hoon; Sohn, Inki; Hwang, Tae-Yeon; Park, Young-Min; Jon, Duk-In; Jeong, Jong-Hyun; Bahk, Won-Myong

    2016-01-01

    ...) with augmentation by blonanserin in schizophrenic patients. aA total of 100 patients with schizophrenia who were partially or completely unresponsive to treatment with an AAP were recruited in this 12-week, open-label, non-comparative, multicenter study...

  19. Rufinamide for refractory focal seizures: an open-label, multicenter European study.

    Science.gov (United States)

    Coppola, Giangennaro; Zamponi, Nelia; Kluger, Gerhard; Mueller, Arndt; Anna Rita, Mazzotta; Parisi, Pasquale; Isone, Claudia; Santoro, Elena; Curatolo, Paolo; Verrotti, Alberto

    2013-01-01

    The present study aimed to assess the efficacy and tolerability of rufinamide as adjunctive drug for the treatment of a large series of children, adolescents and adults with refractory cryptogenic or symptomatic focal epilepsy. Patients were recruited in a prospective, add-on, open-label treatment study from six Italian and one German centers for pediatric and adolescent epilepsy care. Inclusion criteria were: (1) age 3 years or more; (2) diagnosis of cryptogenic or symptomatic focal epilepsy refractory to at least three previous antiepileptic drugs (AEDs), alone or in combination; (3) more than one seizure per month in the last 6 months; (4) use of at least one other AED, but no more than three, at baseline; (5) informed consent from parents and/or caregivers. Sixty-eight patients (40 males, 28 females), aged between 3 and 63 years (mean 19.9 years, median 16.0)±SD 12.58, with cryptogenic (28 pts, 41.2%) or symptomatic focal epilepsy (40 pts, 58.8%), were recruited in the study. After a mean follow-up period of 10.4±10.29 months, twenty-two patients (32.3%) had a 50-99% seizure reduction, and none became seizure-free. Twelve patients (17.6%) had a 25-49% seizure decrease, while in 30 (44.1%) seizure frequency was unchanged. A seizure worsening was reported in 5 patients (7.3%). A better response to rufinamide occurred in frontal lobe seizures (51.6%) and secondary generalized tonic-clonic seizures (50%). Rufinamide was effective against focal-onset seizures, particularly in the treatment of secondary generalized frontal lobe seizures. Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  20. A multicenter, open-label, 52-week study of 2% rebamipide (OPC-12759) ophthalmic suspension in patients with dry eye.

    Science.gov (United States)

    Kinoshita, Shigeru; Awamura, Saki; Nakamichi, Norihiro; Suzuki, Hiroyuki; Oshiden, Kazuhide; Yokoi, Norihiko

    2014-03-01

    To investigate the efficacy and safety of 2% rebamipide ophthalmic suspension administered 4 times daily for 52 weeks in patients with dry eye. Multicenter (17 sites), open-label, single-arm study. A total of 154 patients with dry eye were enrolled in this study. After a 2-week screening period, patients received 2% rebamipide, instilled as 1 drop in each eye, 4 times daily for 52 weeks. The signs and symptoms measures were assessed at baseline, at weeks 2 and 4, and at every 4 weeks thereafter. The objective signs were fluorescein corneal staining score, lissamine green conjunctival staining score, and tear film break-up time, while subjective symptoms were dry eye-related ocular symptoms (foreign body sensation, dryness, photophobia, eye pain, and blurred vision). The safety variable was the occurrence of adverse events. For all objective signs and subjective symptoms, the scores significantly improved at week 2 compared with baseline (P rebamipide is effective in improving both the objective signs and subjective symptoms of dry eye patients for at least 52 weeks. In addition, 2% rebamipide treatment was generally well tolerated. Copyright © 2014. Published by Elsevier Inc.

  1. Head-to-head comparison of aggressive conventional therapy and three biological treatments and comparison of two de-escalation strategies in patients who respond to treatment: study protocol for a multicenter, randomized, open-label, blinded-assessor, phase 4 study.

    Science.gov (United States)

    Glinatsi, Daniel; Heiberg, Marte S; Rudin, Anna; Nordström, Dan; Haavardsholm, Espen A; Gudbjornsson, Bjorn; Østergaard, Mikkel; Uhlig, Till; Grondal, Gerdur; Hørslev-Petersen, Kim; van Vollenhoven, Ronald; Hetland, Merete L

    2017-04-04

    New targeted therapies and improved treatment strategies have dramatically improved the outcomes of patients with rheumatoid arthritis (RA). However, it is unknown whether different early aggressive interventions can induce stable remission or a low-active disease state that can be maintained with conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy, and whether they differ in efficacy and safety. The Nordic Rheumatic Diseases Strategy Trials And Registries (NORD-STAR) study will assess and compare (1) the proportion of patients who achieve remission in a head-to-head comparison between csDMARD plus glucocorticoid therapy and three different biological DMARD (bDMARD) therapies with different modes of action and (2) two de-escalation strategies in patients who respond to first-line therapy. In a pragmatic, 80-160-week, multicenter, randomized, open-label, assessor-blinded, phase 4 study, 800 patients with early RA (symptom duration less than 24 months) are randomized 1:1:1:1 to one of four different treatment arms: (1) aggressive csDMARD therapy with methotrexate + sulphasalazine + hydroxychloroquine + i.a. glucocorticoids (arm 1A) or methotrexate + prednisolone p.o. (arm 1B), (2) methotrexate + certolizumab-pegol, (3) methotrexate + abatacept, or (4) methotrexate + tocilizumab. The primary clinical endpoint is the proportion of patients reaching Clinical Disease Activity Index (CDAI) remission at week 24. Patients in stable remission over 24 consecutive weeks enter part 2 of the study earliest after 48 weeks. Patients not achieving sustained CDAI remission over 24 consecutive weeks, exit the study after 80 weeks. In part 2, patients are re-randomized to two different de-escalation strategies, either immediate or delayed (after 24 weeks) tapering, followed by cessation of study medication. All patients remain on stable doses of methotrexate. The primary clinical endpoint in part 2 is the proportion of patients

  2. Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial

    Science.gov (United States)

    Costa, Dorcas Lamounier; Costa, Carlos Henrique Nery; de Almeida, Roque Pacheco; de Melo, Enaldo Viera; de Carvalho, Sílvio Fernando Guimarães; Rabello, Ana; de Carvalho, Andréa Lucchesi; Sousa, Anastácio de Queiroz; Leite, Robério Dias; Lima, Simone Soares; Amaral, Thais Alves; Alves, Fabiana Piovesan; Rode, Joelle

    2017-01-01

    Background There is insufficient evidence to support visceral leishmaniasis (VL) treatment recommendations in Brazil and an urgent need to improve current treatments. Drug combinations may be an option. Methods A multicenter, randomized, open label, controlled trial was conducted in five sites in Brazil to evaluate efficacy and safety of (i) amphotericin B deoxycholate (AmphoB) (1 mg/kg/day for 14 days), (ii) liposomal amphotericin B (LAMB) (3 mg/kg/day for 7 days) and (iii) a combination of LAMB (10 mg/kg single dose) plus meglumine antimoniate (MA) (20 mg Sb+5/kg/day for 10 days), compared to (iv) standard treatment with MA (20 mg Sb+5/kg/day for 20 days). Patients, aged 6 months to 50 years, with confirmed VL and without HIV infection were enrolled in the study. Primary efficacy endpoint was clinical cure at 6 months. A planned efficacy and safety interim analysis led to trial interruption. Results 378 patients were randomized to the four treatment arms: MA (n = 112), AmphoB (n = 45), LAMB (n = 109), or LAMB plus MA (n = 112). A high toxicity of AmphoB prompted an unplanned interim safety analysis and this treatment arm was dropped. Per intention-to-treat protocol final analyses of the remaining 332 patients show cure rates at 6 months of 77.5% for MA, 87.2% for LAMB, and 83.9% for LAMB plus MA, without statistically significant differences between the experimental arms and comparator (LAMB: 9.7%; CI95% -0.28 to 19.68, p = 0.06; LAMB plus MA: 6.4%; CI95% -3.93 to 16.73; p = 0.222). LAMB monotherapy was safer than MA regarding frequency of treatment-related adverse events (AE) (p = 0.045), proportion of patients presenting at least one severe AE (p = 0.029), and the proportion of AEs resulting in definitive treatment discontinuation (p = 0.003). Conclusions Due to lower toxicity and acceptable efficacy, LAMB would be a more suitable first line treatment for VL than standard treatment. ClinicalTrials.gov identification number: NCT01310738. Trial registration

  3. Multicenter, open-label, exploratory clinical trial with Rhodiola rosea extract in patients suffering from burnout symptoms

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    Kasper S

    2017-03-01

    Full Text Available Siegfried Kasper,1 Angelika Dienel2 1Universitätsklinik für Psychiatrie und Psychotherapie, Medizinische Universität Wien, Wien, Austria; 2Dr Willmar Schwabe GmbH & Co. KG, Karlsruhe, Germany Purpose: This study is the first clinical trial aiming to explore the clinical outcomes in burnout patients treated with Rhodiola rosea. The reported capacity of R. rosea to strengthen the organism against stress and its good tolerability offer a promising approach in the treatment of stress-related burnout. The aim of the treatment was to increase stress resistance, thus addressing the source rather than the symptoms of the syndrome and preventing subsequent diseases associated with a history of burnout. The objective of the trial was to provide the exploratory data required for planning future randomized trials in burnout patients in order to investigate the clinical outcomes of treatment with R. rosea dry extract in this target group.Methods: The study was planned as an exploratory, open-label, multicenter, single-arm trial. A wide range of rating scales were assessed and evaluated in an exploratory data analysis to generate hypotheses regarding clinical courses and to provide a basis for the planning of subsequent studies. A total of 118 outpatients were enrolled. A daily dose of 400 mg R. rosea extract (WS® 1375, Rosalin was administered over 12 weeks. Clinical outcomes were assessed by the German version of the Maslach Burnout Inventory, Burnout Screening Scales I and II, Sheehan Disability Scale, Perceived Stress Questionnaire, Number Connection Test, Multidimensional Mood State Questionnaire, Numerical Analogue Scales for different stress symptoms and impairment of sexual life, Patient Sexual Function Questionnaire, and the Clinical Global Impression Scales. Results: The majority of the outcome measures showed clear improvement over time. Several parameters had already improved after 1 week of treatment and continued to improve further up to

  4. Multicenter, open-label, exploratory clinical trial with Rhodiola rosea extract in patients suffering from burnout symptoms

    Science.gov (United States)

    Kasper, Siegfried; Dienel, Angelika

    2017-01-01

    Purpose This study is the first clinical trial aiming to explore the clinical outcomes in burnout patients treated with Rhodiola rosea. The reported capacity of R. rosea to strengthen the organism against stress and its good tolerability offer a promising approach in the treatment of stress-related burnout. The aim of the treatment was to increase stress resistance, thus addressing the source rather than the symptoms of the syndrome and preventing subsequent diseases associated with a history of burnout. The objective of the trial was to provide the exploratory data required for planning future randomized trials in burnout patients in order to investigate the clinical outcomes of treatment with R. rosea dry extract in this target group. Methods The study was planned as an exploratory, open-label, multicenter, single-arm trial. A wide range of rating scales were assessed and evaluated in an exploratory data analysis to generate hypotheses regarding clinical courses and to provide a basis for the planning of subsequent studies. A total of 118 outpatients were enrolled. A daily dose of 400 mg R. rosea extract (WS® 1375, Rosalin) was administered over 12 weeks. Clinical outcomes were assessed by the German version of the Maslach Burnout Inventory, Burnout Screening Scales I and II, Sheehan Disability Scale, Perceived Stress Questionnaire, Number Connection Test, Multidimensional Mood State Questionnaire, Numerical Analogue Scales for different stress symptoms and impairment of sexual life, Patient Sexual Function Questionnaire, and the Clinical Global Impression Scales. Results The majority of the outcome measures showed clear improvement over time. Several parameters had already improved after 1 week of treatment and continued to improve further up to the end of the study. The incidence of adverse events was low with 0.015 events per observation day. Discussion The trial reported here was the first to investigate clinical outcomes in patients suffering from burnout

  5. Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial.

    Directory of Open Access Journals (Sweden)

    Gustavo Adolfo Sierra Romero

    2017-06-01

    Full Text Available There is insufficient evidence to support visceral leishmaniasis (VL treatment recommendations in Brazil and an urgent need to improve current treatments. Drug combinations may be an option.A multicenter, randomized, open label, controlled trial was conducted in five sites in Brazil to evaluate efficacy and safety of (i amphotericin B deoxycholate (AmphoB (1 mg/kg/day for 14 days, (ii liposomal amphotericin B (LAMB (3 mg/kg/day for 7 days and (iii a combination of LAMB (10 mg/kg single dose plus meglumine antimoniate (MA (20 mg Sb+5/kg/day for 10 days, compared to (iv standard treatment with MA (20 mg Sb+5/kg/day for 20 days. Patients, aged 6 months to 50 years, with confirmed VL and without HIV infection were enrolled in the study. Primary efficacy endpoint was clinical cure at 6 months. A planned efficacy and safety interim analysis led to trial interruption.378 patients were randomized to the four treatment arms: MA (n = 112, AmphoB (n = 45, LAMB (n = 109, or LAMB plus MA (n = 112. A high toxicity of AmphoB prompted an unplanned interim safety analysis and this treatment arm was dropped. Per intention-to-treat protocol final analyses of the remaining 332 patients show cure rates at 6 months of 77.5% for MA, 87.2% for LAMB, and 83.9% for LAMB plus MA, without statistically significant differences between the experimental arms and comparator (LAMB: 9.7%; CI95% -0.28 to 19.68, p = 0.06; LAMB plus MA: 6.4%; CI95% -3.93 to 16.73; p = 0.222. LAMB monotherapy was safer than MA regarding frequency of treatment-related adverse events (AE (p = 0.045, proportion of patients presenting at least one severe AE (p = 0.029, and the proportion of AEs resulting in definitive treatment discontinuation (p = 0.003.Due to lower toxicity and acceptable efficacy, LAMB would be a more suitable first line treatment for VL than standard treatment. ClinicalTrials.gov identification number: NCT01310738.ClinicalTrials.gov NCT01310738.

  6. Multicenter, open-label, exploratory clinical trial with Rhodiola rosea extract in patients suffering from burnout symptoms.

    Science.gov (United States)

    Kasper, Siegfried; Dienel, Angelika

    2017-01-01

    This study is the first clinical trial aiming to explore the clinical outcomes in burnout patients treated with Rhodiola rosea. The reported capacity of R. rosea to strengthen the organism against stress and its good tolerability offer a promising approach in the treatment of stress-related burnout. The aim of the treatment was to increase stress resistance, thus addressing the source rather than the symptoms of the syndrome and preventing subsequent diseases associated with a history of burnout. The objective of the trial was to provide the exploratory data required for planning future randomized trials in burnout patients in order to investigate the clinical outcomes of treatment with R. rosea dry extract in this target group. The study was planned as an exploratory, open-label, multicenter, single-arm trial. A wide range of rating scales were assessed and evaluated in an exploratory data analysis to generate hypotheses regarding clinical courses and to provide a basis for the planning of subsequent studies. A total of 118 outpatients were enrolled. A daily dose of 400 mg R. rosea extract (WS(®) 1375, Rosalin) was administered over 12 weeks. Clinical outcomes were assessed by the German version of the Maslach Burnout Inventory, Burnout Screening Scales I and II, Sheehan Disability Scale, Perceived Stress Questionnaire, Number Connection Test, Multidimensional Mood State Questionnaire, Numerical Analogue Scales for different stress symptoms and impairment of sexual life, Patient Sexual Function Questionnaire, and the Clinical Global Impression Scales. The majority of the outcome measures showed clear improvement over time. Several parameters had already improved after 1 week of treatment and continued to improve further up to the end of the study. The incidence of adverse events was low with 0.015 events per observation day. The trial reported here was the first to investigate clinical outcomes in patients suffering from burnout symptoms when treated with R

  7. A 64-week, multicenter, open-label study of aripiprazole effectiveness in the management of patients with schizophrenia or schizoaffective disorder in a general psychiatric outpatient setting

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    Chiu Nan-Ying

    2010-09-01

    Full Text Available Abstract Objective To evaluate the overall long-term effectiveness of aripiprazole in patients with schizophrenia in a general psychiatric practice setting in Taiwan. Methods This was a prospective, open-label, multicenter, post-market surveillance study in Taiwanese patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV diagnosis of schizophrenia or schizoaffective disorder requiring a switch in antipsychotic medication because current medication was not well tolerated and/or clinical symptoms were not well controlled. Eligible patients were titrated to aripiprazole (5-30 mg/day over a 12-week switching phase, during which their previous medication was discontinued. Patients could then enter a 52-week, long-term treatment phase. Aripiprazole was flexibly dosed (5-30 mg/day at the discretion of the treating physicians. Efficacy was assessed using the Clinical Global Impression scale Improvement (CGI-I score, the Clinical Global Impression scale Severity (CGI-S score, The Brief Psychiatry Rating Scale (BPRS, and the Quality of Life (QOL scale, as well as Preference of Medicine (POM ratings by patients and caregivers. Safety and tolerability were also assessed. Results A total of 245 patients were enrolled and switched from their prior antipsychotic medications, and 153 patients entered the 52-week extension phase. In all, 79 patients (32.2% completed the study. At week 64, the mean CGI-I score was 3.10 and 64.6% of patients who showed response. Compared to baseline, scores of CGI-S, QOL, and BPRS after 64 weeks of treatment also showed significant improvements. At week 12, 65.4% of subjects and 58.9% of caregivers rated aripiprazole as better than the prestudy medication on the POM. The most frequently reported adverse events (AEs were headache, auditory hallucinations and insomnia. A total of 13 patients (5.3% discontinued treatment due to AEs. No statistically significant changes were noted with respect to

  8. An open-label, multicenter evaluation of the long-term safety and efficacy of risperidone in adolescents with schizophrenia

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    Pandina Gahan

    2012-06-01

    Full Text Available Abstract Background Data on the long-term efficacy, safety, and tolerability of risperidone in adolescents with schizophrenia are limited. The objective of this study was to evaluate the efficacy and safety of maintenance risperidone treatment in adolescents with schizophrenia. Methods This open-label study of adolescents aged 13 to 17 years with schizophrenia was a single extension study of two short-term double-blind risperidone studies and also enrolled subjects directly in open-label risperidone treatment. The risperidone dose was flexible and ranged from 2 to 6 mg/day. Most subjects enrolled for 6 months; a subset enrolled for 12 months. Assessment tools included the Positive and Negative Syndrome Scale total and factor scores, Clinical Global Impressions, Children’s Global Assessment Scale, adverse event (AE monitoring, vital signs, laboratory testing, and extrapyramidal symptom rating scales. Results A total of 390 subjects were enrolled; 48 subjects had received placebo in a previous double-blind study; 292 subjects had received risperidone as part of their participation in one of two previous controlled studies; and 50 subjects were enrolled directly for this study. A total of 279 subjects enrolled for 6 months of treatment, and 111 subjects enrolled for 12 months of treatment. Overall, 264 (67.7% subjects completed this study: 209 of the 279 subjects (75% in the 6-month group and 55 of the 111 subjects (50% in the 12-month group. The median mode dose was 3.8 mg/day. At 6 months, all three groups experienced improvement from open-label baseline in symptoms of schizophrenia as well as general assessments of global functioning. Improvements were generally maintained for the duration of treatment. The most common AEs (≥10% of subjects were somnolence, headache, weight increase, hypertonia, insomnia, tremor, and psychosis. Potentially prolactin-related AEs (PPAEs were reported by 36 (9% subjects. The AE profile in this study was

  9. Efficacy and safety of a flexible extended regimen of ethinylestradiol/drospirenone for the treatment of dysmenorrhea: a multicenter, randomized, open-label, active-controlled study.

    Science.gov (United States)

    Momoeda, Mikio; Kondo, Masami; Elliesen, Joerg; Yasuda, Masanobu; Yamamoto, Shigetomo; Harada, Tasuku

    2017-01-01

    Dysmenorrhea is a common condition in women, which is characterized by menstrual pain. Low-dose estrogen/progestin combined oral contraceptives have been shown to reduce the severity of dysmenorrhea symptoms, and a 28-day cyclic regimen of ethinylestradiol/drospirenone (28d regimen) is approved for this indication in Japan. The aim of this study was to assess the safety and efficacy of a flexible extended regimen of ethinylestradiol/drospirenone (flexible regimen) in Japanese women with dysmenorrhea. This multicenter, open-label study was performed in Japanese women with dysmenorrhea who, after a baseline observational phase, were randomized to receive ethinylestradiol 20 μg/drospirenone 3 mg in a flexible regimen (one tablet each day for 24-120 days followed by a 4-day tablet-free interval) or in the standard 28d regimen (one tablet each day for 24 days, followed by 4 days of placebo tablets for six cycles). The primary endpoint was the number of days with dysmenorrhea of at least mild intensity over a 140-day evaluation period. Dysmenorrhea scores, bleeding patterns, and other pain-related parameters were also assessed. A total of 216 women (mean age 29.7 years) were randomized to the flexible regimen (n=108) or 28d regimen (n=108) and 212 were included in the full analysis sets (flexible regimen, n=105; 28d regimen, n=107). Women in the flexible-regimen group reported a mean of 3.4 fewer days with dysmenorrheic pain than women in the 28d-regimen group, with similar decreases in disease severity reported in both treatment groups. According to the investigators, 64.8% and 59.4% of women in the flexible-regimen and 28d-regimen treatment groups had "very much improved" or "much improved" disease, while 54.3% and 50.9% of patients reported being "very much satisfied" or "much satisfied" with their treatment, respectively. In Japanese women with dysmenorrhea, a flexible extended regimen of ethinylestradiol/drospirenone decreased the number of days with dysmenorrheic

  10. Open-label, randomized, comparative, phase III study on effects of reducing steroid use in combination with Palonosetron.

    Science.gov (United States)

    Komatsu, Yoshito; Okita, Kenji; Yuki, Satoshi; Furuhata, Tomohisa; Fukushima, Hiraku; Masuko, Hiroyuki; Kawamoto, Yasuyuki; Isobe, Hiroshi; Miyagishima, Takuto; Sasaki, Kazuaki; Nakamura, Michio; Ohsaki, Yoshinobu; Nakajima, Junta; Tateyama, Miki; Eto, Kazunori; Minami, Shinya; Yokoyama, Ryoji; Iwanaga, Ichiro; Shibuya, Hitoshi; Kudo, Mineo; Oba, Koji; Takahashi, Yasuo

    2015-07-01

    The purpose of this study is to compare the efficacy of a single administration of dexamethasone (DEX) on day 1 against DEX administration on days 1-3 in combination with palonosetron (PALO), a second-generation 5-HT3 receptor antagonist, for chemotherapy-induced nausea and vomiting (CINV) in non-anthracycline and cyclophosphamide (AC) moderately-emetogenic chemotherapy (MEC). This phase III trial was conducted with a multi-center, randomized, open-label, non-inferiority design. Patients who received non-AC MEC as an initial chemotherapy were randomly assigned to either a group administered PALO (0.75 mg, i.v.) and DEX (9.9 mg, i.v.) prior to chemotherapy (study treatment group), or a group administered additional DEX (8 mg, i.v. or p.o.) on days 2-3 (control group). The primary endpoint was complete response (CR) rate. The CR rate difference was estimated by logistic regression with allocation factors as covariates. The non-inferiority margin was set at -15% (study treatment group - control group). From April 2011 to March 2013, 305 patients who received non-AC MEC were randomly allocated to one of two study groups. Overall, the CR rate was 66.2% in the study treatment group (N = 151) and 63.6% in the control group (N = 154). PALO plus DEX day 1 was non-inferior to PALO plus DEX days 1-3 (difference, 2.5%; 95% confidence interval [CI]: -7.8%-12.8%; P-value for non-inferiority test = 0.0004). There were no differences between the two groups in terms of complete control rate (64.9 vs 61.7%) and total control rate (49.7% vs 47.4%). Anti-emetic DEX administration on days 2-3 may be eliminated when used in combination with PALO in patients receiving non-AC MEC.

  11. A Multicenter, Open-Label Trial to Evaluate the Quality of Life in Adults with ADHD Treated with Long-Acting Methylphenidate (OROS MPH): Concerta Quality of Life (CONQoL) Study

    Science.gov (United States)

    Mattos, Paulo; Rodrigues Louza, Mario; Fernandes Palmini, Andre Luis; de Oliveira, Irismar Reis; Lopes Rocha, Fabio

    2013-01-01

    The available literature provides few studies on the effectiveness of methylphenidate in improving quality of life in individuals with ADHD. Objective: To assess the effectiveness of Methyphenidate OROS formulation (OROS MPH) through QoL in adults with ADHD. Method: A 12-week, multicenter, open-label trial involving 60 patients was used. The…

  12. Phase II open-label study to assess efficacy and safety of lenalidomide in combination with cetuximab in KRAS-mutant metastatic colorectal cancer.

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    Salvatore Siena

    Full Text Available This study aimed to assess the efficacy and safety of combination treatment with lenalidomide and cetuximab in KRAS-mutant metastatic colorectal cancer patients. This was a phase II multicenter, open-label trial comprising a safety lead-in phase (phase IIa to determine the maximum tolerated dose, and a randomized proof of concept phase (phase IIb to determine the response rate of lenalidomide plus cetuximab combination therapy. Phase IIa treatment comprised oral lenalidomide (starting dose 25 mg/day and intravenous cetuximab (400 mg/m(2 followed by weekly 250 mg/m(2 in 28-day cycles. In phase IIb patients were randomized to either the phase IIa treatment schedule of lenalidomide plus cetuximab combination therapy or lenalidomide 25 mg/day monotherapy. Eight patients were enrolled into phase IIa. One patient developed a dose-limiting toxicity and the maximum tolerated dose of lenalidomide was determined at 25 mg/day. Forty-three patients were enrolled into phase IIb proof of concept. Best response was stable disease in 9 patients and study enrollment was terminated prematurely due to lack of efficacy in both treatment arms and failure to achieve the planned response objective. The majority of adverse events were grade 1 and 2. In both phases, the adverse events most commonly attributed to any study drugs were fatigue, rash and other skin disorders, diarrhea, nausea, and stomatitis. Thirty-nine deaths occurred; none was related to study drug. The combination of lenalidomide and cetuximab appeared to be well tolerated but did not have clinically meaningful activity in KRAS-mutant metastatic colorectal cancer patients.Clinicaltrials.gov NCT01032291.

  13. An Open-Label Uncontrolled, Multicenter Study for the Evaluation of the Efficacy and Safety of the Dermal Filler Princess VOLUME in the Treatment of Nasolabial Folds

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    Daisy Kopera

    2015-01-01

    Full Text Available The dermal filler Princess VOLUME is a highly cross-linked, viscoelastic hyaluronic acid injectable gel implant used for aesthetic treatment. To evaluate the efficacy and safety of Princess VOLUME in the treatment of nasolabial folds, an open-label uncontrolled, multicenter study was conducted. Forty-eight subjects were recruited who had moderate to deep wrinkles, according to the Modified Fitzpatrick Wrinkle Scale (MFWS. Subjects received Princess VOLUME in both nasolabial folds at Day 0. Nasolabial fold severity was evaluated at 30, 90, 180, and 270 days after treatment, using the MFWS and the Global Aesthetic Improvement Scale (GAIS. Adverse events and treatment site reactions were recorded. Among the 48 subjects, 93.8% were female with a median age of 52 years. There were significant improvements (P<0.0001 in the MFWS scores at 30, 180, and 270 days after treatment compared with those at baseline, with a mean decrease of 1.484 (±0.408, 1.309 (±0.373, and 1.223 (±0.401, respectively; hence the primary endpoint was achieved and clinical efficacy demonstrated. Princess VOLUME was well tolerated, and most adverse events were injection site reactions of mild to moderate severity. Subject satisfaction (97.9%, subject recommendation of the treatment (93.6%, and investigators GAIS scores (97.9% improvement were high.

  14. The MANDELA study: A multicenter, randomized, open-label, parallel group trial to refine the use of everolimus after heart transplantation.

    Science.gov (United States)

    Deuse, Tobias; Bara, Christoph; Barten, Markus J; Hirt, Stephan W; Doesch, Andreas O; Knosalla, Christoph; Grinninger, Carola; Stypmann, Jörg; Garbade, Jens; Wimmer, Peter; May, Christoph; Porstner, Martina; Schulz, Uwe

    2015-11-01

    In recent years a series of trials has sought to define the optimal protocol for everolimus-based immunosuppression in heart transplantation, with the goal of minimizing exposure to calcineurin inhibitors (CNIs) and harnessing the non-immunosuppressive benefits of everolimus. Randomized studies have demonstrated that immunosuppressive potency can be maintained in heart transplant patients receiving everolimus despite marked CNI reduction, although very early CNI withdrawal may be inadvisable. A potential renal advantage has been shown for everolimus, but the optimal time for conversion and the adequate reduction in CNI exposure remain to be defined. Other reasons for use of everolimus include a substantial reduction in the risk of cytomegalovirus infection, and evidence for inhibition of cardiac allograft vasculopathy, a major cause of graft loss. The ongoing MANDELA study is a 12-month multicenter, randomized, open-label, parallel-group study in which efficacy, renal function and safety are compared in approximately 200 heart transplant patients. Patients receive CNI therapy, steroids and everolimus or mycophenolic acid during months 3 to 6 post-transplant, and are then randomized at month 6 post-transplant (i) to convert to CNI-free immunosuppression with everolimus and mycophenolic acid or (ii) to continue reduced-exposure CNI, with concomitant everolimus. Patients are then followed to month 18 post-transplant The rationale and expectations for the trial and its methodology are described herein.

  15. Blonanserin Augmentation of Atypical Antipsychotics in Patients with Schizophrenia-Who Benefits from Blonanserin Augmentation?: An Open-Label, Prospective, Multicenter Study.

    Science.gov (United States)

    Woo, Young Sup; Park, Joo Eon; Kim, Do-Hoon; Sohn, Inki; Hwang, Tae-Yeon; Park, Young-Min; Jon, Duk-In; Jeong, Jong-Hyun; Bahk, Won-Myong

    2016-07-01

    The purpose of this study was to investigate the efficacy and tolerability of atypical antipsychotics (AAPs) with augmentation by blonanserin in schizophrenic patients. aA total of 100 patients with schizophrenia who were partially or completely unresponsive to treatment with an AAP were recruited in this 12-week, open-label, non-comparative, multicenter study. Blonanserin was added to their existing AAP regimen, which was maintained during the study period. Efficacy was primarily evaluated using the Positive and Negative Syndrome Scale (PANSS) at baseline and at weeks 2, 4, 8, and 12. Predictors for PANSS response (≥20% reduction) were investigated. The PANSS total score was significantly decreased at 12 weeks of blonanserin augmentation (-21.0±18.1, F=105.849, pblonanserin occurred in 17 patients (17.0%); 4 of these patients dropped out due to adverse events. The patients who benefited the most from blonanserin were those with severe symptoms despite a treatment with a higher dose of AAP. Blonanserin augmentation could be an effective strategy for patients with schizophrenia who were partially or completely unresponsive to treatment with an AAP.

  16. Efficacy and safety of telithromycin 800 mg once daily for 7 days in community-acquired pneumonia: an open-label, multicenter study

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    Dunbar Lala M

    2005-05-01

    Full Text Available Abstract Background Community-acquired pneumonia (CAP remains a major cause of morbidity and mortality throughout the world. Telithromycin (a new ketolide has shown good in vitro activity against the key causative pathogens of CAP, including S pneumoniae resistant to penicillin and/or macrolides. Methods The efficacy and safety of telithromycin 800 mg orally once daily for 7 days in the treatment of CAP were assessed in an open-label, multicenter study of 442 adults. Results Of 149 microbiologically evaluable patients, 57 (9 bacteremic had Streptococcus pneumoniae. Of the 57 S pneumoniae pathogens isolated in these patients, 9 (2 bacteremic were penicillin- or erythromycin-resistant; all 57 were susceptible to telithromycin and were eradicated. Other pathogens and their eradication rates were: Haemophilus influenzae (96%, Moraxella catarrhalis (100%, Staphylococcus aureus (80%, and Legionella spp. (100%. The overall bacteriologic eradication rate was 91.9%. Of the 357 clinically evaluable patients, clinical cure was achieved in 332 (93%. In the 430 patients evaluable for safety, the most common drug-related adverse events were diarrhea (8.1% and nausea (5.8%. Conclusion Telithromycin 800 mg once daily for 7 days is an effective and well-tolerated oral monotherapy and offers a new treatment option for CAP patients, including those with resistant S pneumoniae.

  17. Conversion to lanthanum carbonate monotherapy effectively controls serum phosphorus with a reduced tablet burden: a multicenter open-label study

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    Matalon Albert

    2011-09-01

    Full Text Available Abstract Background Lanthanum carbonate (FOSRENOL® is an effective, well-tolerated phosphate binder. The ability of lanthanum to reduce serum phosphorus levels to ≤5.5 mg/dL in patients with end-stage renal disease (ESRD was assessed in a clinical practice setting. Methods A 16-week, phase IV study enrolled 2763 patients at 223 US sites to evaluate the efficacy of lanthanum carbonate in controlling serum phosphorus in patients with ESRD, and patient and physician satisfaction with, and preference for, lanthanum carbonate after conversion from other phosphate-binder medications. Patients received lanthanum carbonate prescriptions from physicians. These prescriptions were filled at local pharmacies rather than obtaining medication at the clinical trial site. Changes from serum phosphorus baseline values were analyzed using paired t tests. Patient and physician preferences for lanthanum carbonate versus previous medications were assessed using binomial proportion tests. Satisfaction was analyzed using the McNemar test. Daily dose, tablet burden, and laboratory values including albumin-adjusted serum calcium, calcium × phosphorus product, and parathyroid hormone levels were secondary endpoints. Results Serum phosphorus control (≤5.5 mg/dL was effectively maintained in patients converting to lanthanum carbonate monotherapy; 41.6% of patients had controlled serum phosphate levels at 16 weeks. Patients and physicians expressed markedly higher satisfaction with lanthanum carbonate, and preferred lanthanum carbonate over previous medication. There were significant reductions in daily dose and daily tablet burden after conversion to lanthanum carbonate. Conclusions Serum phosphorus levels were effectively maintained in patients converted from other phosphate-binder medications to lanthanum carbonate, with increased satisfaction and reduced tablet burden. Trial Registration ClinicalTrials.gov: NCT0016012

  18. A multicenter, open-label study of the efficacy and safety of telmisartan in mild to moderate hypertensive patients

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    Plavnik Frida Liane

    2002-01-01

    Full Text Available OBJECTIVE: To evaluate the efficacy and tolerability of telmisartan, given once a day to patients with mild to moderate hypertension, as well as to assess the 24-hour blood pressure profile with ABPM. METHODS: Initially, 163 patients over 18 were selected, regardless of sex, with blood pressure levels >140/90mmHg at visit 1, which was confirmed at visit 2. One hundred thirty-four patients completed the study. After a 4-week placebo run-in phase, telmisartan 40mg/daily was given for 6 weeks. In those patients whose blood pressure (BP levels were lower than 140/90mmHg, the same dosage was kept for an additional period of 6 weeks. For those who had BP higher than 140/90mmHg, the dosage was increased to 80mg/daily. Sixty-two patients were included in a subgroup that underwent ABPM 3 different times during the study. RESULTS: In the overall group, blood pressure reduction ranged from 162.3±14.5/101.3±5.75 mmHg (baseline to 147.3±20.1/90.8±10.9 mmHg (week 12 (p<0.05. Mean blood pressure decreases were 14.4mmHg for systolic BP and 10.3mmHg for diastolic BP, after 12 weeks of active treatment. A subanalysis showed that 47 (35% patients took telmisartan 40mg throughout the study and 81 (65% had the dosage increased to 80mg daily. Using ABPM, an 8-mmHg reduction in systolic BP as well as a 5-mmHg reduction in diastolic BP were observed, when compared with baseline values in the final 6 hours (18-24 hours after the last dose of study medication. CONCLUSION: Our results confirm that telmisartan given once a day is effective in reducing blood pressure levels in mild to moderate hypertensive patients. This reduction occurs in a sustained and gradual manner during a 24-hour period confirmed by ABPM.

  19. A multi-center, prospective, open-label, 8-week study of certoparin for anticoagulation during maintenance hemodialysis – the membrane study

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    Dorsch Oliver

    2012-06-01

    Full Text Available Abstract Background Adequate anticoagulation is prerequisite for effective hemodialysis to prevent clotting in the extracorporeal circuit. We aimed providing first data on the efficacy and safety of the low-molecular-weight heparin certoparin in this setting. Methods Multicenter, open-label, 8-week trial. Patients received a single dose of 3,000 IU certoparin i.v. with additional titration steps of 600 IU and/or continuous infusion if necessary. Results 120 patients were screened, 109 enrolled (median age 71; range 26–90 years and 106 available for efficacy analyses. The percentage of unsatisfactory dialysis results at 8 weeks due to clotting or bleeding, was 1.9% (n = 2/106; 95% confidence interval [CI] 0.23–6.65%; no major bleeding. 1.9% had moderate/severe clotting in the lines/bubble catcher and 2.8% in the dialyser at week 8. 15.7 ± 14.3% of the dialysis filters’ visual surface area was showing redness. In subgroups of patients receiving median doses of 3000 ± 0, 3000 (2400–6000 and 4200 (3000–6600 IU, plasma aXa levels at baseline, 4 and 8 weeks were 0.24 [95%CI 0.21–0.27], 0.33 [0.27–0.40] and 0.38 [0.33–0.45] aXa IU/ml at 2 h. C48h was 0.01 [0.01–0.02] aXa IU at all visits. At baseline and 4 weeks AUC0-48h was 2.66 [2.19–3.24] and 3.66 [3.00–4.45] aXa IU*h/ml. In 3.0% of dialyses (n = 83/2724 prolonged fistula compression times were documented. Eight patients (7.34% had at least one episode of minor bleeding. 4 85.3% of patients had any adverse event, 9.2% were serious without suspected drug relation; and in 32 patients a drug-relation was suspected. Conclusions Certoparin appears effective and safe for anticoagulation in patients undergoing maintenance hemodialysis.

  20. Efficacy and tolerability of carbamazepine for the treatment of painful diabetic neuropathy in adults: a 12-week, open-label, multicenter study

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    Saeed T

    2014-07-01

    Full Text Available Tariq Saeed,1 Muhammad Nasrullah,2 Adnan Ghafoor,3 Riaz Shahid,4 Nadeem Islam,5 Mohammad Usman Khattak,6 Neeta Maheshwary,7 Ahson Siddiqi,7 Muhammad Athar Khan81Pakistan Telecommunication Company Ltd, Karachi, Pakistan; 2Cavalary Hospital, Gulberg, Lahore, Pakistan; 3Fauji Foundation Hospital, Rawalpindi, Pakistan; 4Dr Riaz Shahid Clinic, Peshawar Cantt, Peshawar, Pakistan; 5Punjab Employs Social Security Institution, Islamabad, Pakistan; 6Medical B Unit, Hayat Abad Medical Complex, Peshawar, Pakistan; 7Novartis Pharma Pakistan, Karachi, Pakistan; 8Department of Medical Education, King Saud bin Abdulaziz University, Riyadh, Kingdom of Saudi ArabiaObjective: Anticonvulsants are increasingly being used in the symptomatic management of several neuropathic pain disorders. The present observational study was designed to evaluate the efficacy, tolerability, and quality of life (QoL of carbamazepine use for 12 weeks in patients with painful diabetic neuropathy, in Pakistan.Methods: This was a 12-week, multicenter, open-label, uncontrolled trial in adult type 2 diabetic patients (aged 18–65 years suffering from clinically confirmed neuropathic pain (Douleur Neuropathique en 4 [DN4] score ≥4. Change in neuropathic pain at week 12 compared with baseline was assessed using the Brief Pain Inventory Scale–Short Form (pain severity score and pain interference score. QoL was determined by the American Chronic Pain Association QoL scale. Safety was assessed based on patient reported adverse events (AEs and serious AEs.Results: Of the total 500 screened patients, 452 enrolled and completed the study. The mean (± standard deviation [SD] pain interference score decreased from 4.5±2.0 at baseline to 3.1±1.9 at week 12 (P<0.001. The mean (± SD pain severity score decreased from 5.8±2.0 at baseline to 3.6±2.2 at week 12 (P<0.001. There was a decrease of ≥30% in the pain severity score between visits. The mean (± SD QoL scale score improved from 5.9±1

  1. Efficacy and tolerability of carbamazepine for the treatment of painful diabetic neuropathy in adults: a 12-week, open-label, multicenter study

    Science.gov (United States)

    Saeed, Tariq; Nasrullah, Muhammad; Ghafoor, Adnan; Shahid, Riaz; Islam, Nadeem; Khattak, Mohammad Usman; Maheshwary, Neeta; Siddiqi, Ahson; Khan, Muhammad Athar

    2014-01-01

    Objective Anticonvulsants are increasingly being used in the symptomatic management of several neuropathic pain disorders. The present observational study was designed to evaluate the efficacy, tolerability, and quality of life (QoL) of carbamazepine use for 12 weeks in patients with painful diabetic neuropathy, in Pakistan. Methods This was a 12-week, multicenter, open-label, uncontrolled trial in adult type 2 diabetic patients (aged 18–65 years) suffering from clinically confirmed neuropathic pain (Douleur Neuropathique en 4 [DN4] score ≥4). Change in neuropathic pain at week 12 compared with baseline was assessed using the Brief Pain Inventory Scale–Short Form (pain severity score and pain interference score). QoL was determined by the American Chronic Pain Association QoL scale. Safety was assessed based on patient reported adverse events (AEs) and serious AEs. Results Of the total 500 screened patients, 452 enrolled and completed the study. The mean (± standard deviation [SD]) pain interference score decreased from 4.5±2.0 at baseline to 3.1±1.9 at week 12 (P<0.001). The mean (± SD) pain severity score decreased from 5.8±2.0 at baseline to 3.6±2.2 at week 12 (P<0.001). There was a decrease of ≥30% in the pain severity score between visits. The mean (± SD) QoL scale score improved from 5.9±1.6 at baseline to 8.0±1.7 at week 12. A total of ten (2.2%) patients reported AEs during the study period. No patient discontinued the study due to AEs. Conclusion In this real-life experience study, carbamazepine, when prescribed for 12 weeks to adult diabetic patients suffering from neuropathic pain, showed pain-relief effect, with reduced mean pain severity and mean pain interference scores and with improved QoL and good tolerability profile. PMID:25061334

  2. A phase 1/2, open-label study evaluating twice-daily administration of momelotinib in myelofibrosis

    Science.gov (United States)

    Gupta, Vikas; Mesa, Ruben A.; Deininger, Michael W.N.; Rivera, Candido E.; Sirhan, Shireen; Brachmann, Carrie Baker; Collins, Helen; Kawashima, Jun; Xin, Yan; Verstovsek, Srdan

    2017-01-01

    Momelotinib, a small-molecule inhibitor of Janus kinase 1 and Janus kinase 2, has demonstrated efficacy in myelofibrosis patients with 300 mg, once-daily dosing. This open-label, non-randomized, phase 1/2 study evaluated the safety and therapeutic benefit of momelotinib with twice-daily dosing. A total of 61 subjects with primary myelofibrosis or post–polycythemia vera/post–essential thrombocythemia myelofibrosis with intermediate- or high-risk disease received momelotinib. A phase 1 dose escalation identified 200 mg twice daily as the optimal dose to be expanded in phase 2. The most frequent adverse events were diarrhea (45.9%), peripheral neuropathy (44.3%), thrombocytopenia (39.3%), and dizziness (36.1%), the latter primarily due to a first-dose effect. The response assessment according to the 2006 International Working Group criteria (≥8 weeks duration at any time point) demonstrated spleen response by palpation of 72% (36/50) and anemia response of 45% (18/40). Spleen response by magnetic resonance imaging obtained at 24 weeks was 45.8% (27/59) for all subjects and 54.0% (27/50) for those with palpable splenomegaly at baseline. The symptoms of myelofibrosis were improved in most subjects. Cytokine analysis showed a rapid decline in interleukin-6 with momelotinib treatment, and a slower reduction in other inflammatory cytokines. In the subgroup of subjects with the JAK2V617F mutation at baseline (n=41), momelotinib significantly reduced the allele burden by 21.1% (median) at 24 weeks. These results provide evidence of tolerability and a potential therapeutic activity of momelotinib for subjects that support further evaluation in ongoing, phase 3 randomized trials. (clinicaltrials. gov identifier:01423058). PMID:27634203

  3. Clarithromycin Plus Intravenous Immunoglobulin Therapy Can Reduce the Relapse Rate of Kawasaki Disease: A Phase 2, Open-Label, Randomized Control Study.

    Science.gov (United States)

    Nanishi, Etsuro; Nishio, Hisanori; Takada, Hidetoshi; Yamamura, Kenichiro; Fukazawa, Mitsuharu; Furuno, Kenji; Mizuno, Yumi; Saigo, Kenjiro; Kadoya, Ryo; Ohbuchi, Noriko; Onoe, Yasuhiro; Yamashita, Hironori; Nakayama, Hideki; Hara, Takuya; Ohno, Takuro; Takahashi, Yasuhiko; Hatae, Ken; Harada, Tatsuo; Shimose, Takayuki; Kishimoto, Junji; Ohga, Shouichi; Hara, Toshiro

    2017-07-06

    We previously reported that biofilms and innate immunity contribute to the pathogenesis of Kawasaki disease. Therefore, we aimed to assess the efficacy of clarithromycin, an antibiofilm agent, in patients with Kawasaki disease. We conducted an open-label, multicenter, randomized, phase 2 trial at 8 hospitals in Japan. Eligible patients included children aged between 4 months and 5 years who were enrolled between days 4 and 8 of illness. Participants were randomly allocated to receive either intravenous immunoglobulin (IVIG) or IVIG plus clarithromycin. The primary end point was the duration of fever after the initiation of IVIG treatment. Eighty-one eligible patients were randomized. The duration of the fever did not differ between the 2 groups (mean±SD, 34.3±32.4 and 31.1±31.1 hours in the IVIG plus clarithromycin group and the IVIG group, respectively [P=0.66]). The relapse rate of patients in the IVIG plus clarithromycin group was significantly lower than that in the IVIG group (12.5% versus 30.8%, P=0.046). No serious adverse events occurred during the study period. In a post hoc analysis, the patients in the IVIG plus clarithromycin group required significantly shorter mean lengths of hospital stays than those in the IVIG group (8.9 days versus 10.3 days, P=0.049). Although IVIG plus clarithromycin therapy failed to shorten the duration of fever, it reduced the relapse rate and shortened the duration of hospitalization in patients with Kawasaki disease. URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000015437. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  4. STRATEGIC-1: A multiple-lines, randomized, open-label GERCOR phase III study in patients with unresectable wild-type RAS metastatic colorectal cancer.

    Science.gov (United States)

    Chibaudel, Benoist; Bonnetain, Franck; Tournigand, Christophe; de Larauze, Marine Hug; de Gramont, Armand; Laurent-Puig, Pierre; Paget, Jérôme; Hadengue, Alexandra; Notelet, Dominique; Benetkiewicz, Magdalena; André, Thierry; de Gramont, Aimery

    2015-07-04

    The management of unresectable metastatic colorectal cancer (mCRC) is a comprehensive treatment strategy involving several lines of therapy, maintenance, salvage surgery, and treatment-free intervals. Besides chemotherapy (fluoropyrimidine, oxaliplatin, irinotecan), molecular-targeted agents such as anti-angiogenic agents (bevacizumab, aflibercept, regorafenib) and anti-epidermal growth factor receptor agents (cetuximab, panitumumab) have become available. Ultimately, given the increasing cost of new active compounds, new strategy trials are needed to define the optimal use and the best sequencing of these agents. Such new clinical trials require alternative endpoints that can capture the effect of several treatment lines and be measured earlier than overall survival to help shorten the duration and reduce the size and cost of trials. STRATEGIC-1 is an international, open-label, randomized, multicenter phase III trial designed to determine an optimally personalized treatment sequence of the available treatment modalities in patients with unresectable RAS wild-type mCRC. Two standard treatment strategies are compared: first-line FOLFIRI-cetuximab, followed by oxaliplatin-based second-line chemotherapy with bevacizumab (Arm A) vs. first-line OPTIMOX-bevacizumab, followed by irinotecan-based second-line chemotherapy with bevacizumab, and by an anti-epidermal growth factor receptor monoclonal antibody with or without irinotecan as third-line treatment (Arm B). The primary endpoint is duration of disease control. A total of 500 patients will be randomized in a 1:1 ratio to one of the two treatment strategies. The STRATEGIC-1 trial is designed to give global information on the therapeutic sequences in patients with unresectable RAS wild-type mCRC that in turn is likely to have a significant impact on the management of this patient population. The trial is open for inclusion since August 2013. STRATEGIC-1 is registered at Clinicaltrials.gov: NCT01910610, 23 July, 2013

  5. Efficacy of Rituximab in Refractory Inflammatory Myopathies Associated with Anti- Synthetase Auto-Antibodies: An Open-Label, Phase II Trial.

    Directory of Open Access Journals (Sweden)

    Yves Allenbach

    Full Text Available Anti-synthetase syndrome (anti-SS is frequently associated with myositis and interstitial lung disease (ILD. We evaluated prospectively, in a multicenter, open-label, phase II study, the efficacy of rituximab on muscle and lung outcomes.Patients were enrolled if they were refractory to conventional treatments (prednisone and at least 2 immunosuppressants. They received 1 g of rituximab at D0, D15, and M6. The primary endpoint was muscular improvement based on manual muscular testing (MMT10, Kendall score in 10 muscles at M12. Secondary endpoints were normalization of creatine kinase (CK level, ILD improvement based on forced vital capacity and/or diffuse capacity for carbon monoxide, and number and/or doses of associated immunosuppressants.Twelve patients were enrolled, and 10 completed the study. Only 2 patients presented an improvement of at least 4 points on at least two muscle groups (primary end-point. Overall, seven patients had an increase of at least 4 points on MMT10. CK level decreased from 399 IU/L (range, 48-11,718 to 74.5 IU/L (range, 40-47,857. Corticosteroid doses decreased from 52.5 mg/d (range, 10-70 to 9 mg/d (range, 7-65 and six patients had a decrease in the burden of their associated immunosuppressants. At baseline, all 10 patients presented with ILD. At M12, improvement of ILD was observed in 5 out of the 10 patients, stabilization in 4, and worsening in 1.This pilot study of rituximab treatment in patients with refractory anti-SS provided data on evolution of muscular and pulmonary parameters. Rituximab should now be evaluated in a larger, controlled study for this homogenous group of patients.Clinicaltrials.gov NCT00774462.

  6. Antithrombotic properties of rafigrelide: a phase 1, open-label, non-randomised, single-sequence, crossover study.

    Science.gov (United States)

    Balasubramaniam, K; Viswanathan, G; Dragone, J; Grose-Hodge, R; Martin, P; Troy, S; Preston, P; Zaman, A G

    2014-07-03

    Platelets play a central role in atherothrombotic events. We investigated the effect of a novel platelet-lowering agent, rafigrelide, on thrombus formation and characteristics. In this phase 1, open-label, non-randomised, single-sequence, crossover study, healthy male volunteers received rafigrelide for 14 days (Period 1). Following a ≥6-week washout period, they then received rafigrelide + acetylsalicylic acid (ASA) for 14 days (Period 2). Thrombus formation was assessed ex vivo using the Badimon perfusion chamber, and thrombus characteristics were assessed using thromboelastography. A total of 15 volunteers were enrolled in the study and were assigned to Panel A or Panel B, which had different schedules of assessments. In Panel A, after treatment with rafigrelide alone (Period 1), mean (± standard deviation) platelet count was reduced from 283 (± 17) × 10⁹/l at Day 1, to 125 (± 47) × 10⁹/l at Day 14 (n=6) and thrombus area reduced under high and low shear conditions. Reductions in thrombus area under high shear conditions correlated with reductions in platelet count (r²=0.11, p=0.022; n=12). Rafigrelide treatment prolonged clot formation time and reduced clot strength. The addition of ASA to rafigrelide (Period 2) had no additional effect on platelet count or thrombus area under high or low shear conditions. Similar results were seen in Panel B for all parameters. The most common adverse events (≥3 participants per period) were thrombocytopenia and headache. While confirming the platelet-lowering effects of rafigrelide, this early phase study also indicates that rafigrelide has antithrombotic properties under both high and low shear conditions.

  7. First-dose effects of fingolimod after switching from injectable therapies in the randomized, open-label, multicenter, Evaluate Patient OutComes (EPOC) study in relapsing multiple sclerosis.

    Science.gov (United States)

    Hughes, Bruce; Cascione, Mark; Freedman, Mark S; Agius, Mark; Kantor, Daniel; Gudesblatt, Mark; Goldstick, Lawrence P; Agashivala, Neetu; Schofield, Lesley; McCague, Kevin; Hashmonay, Ron; Barbato, Luigi

    2014-09-01

    In pivotal phase 3 studies, fingolimod treatment initiation was associated with a transient reduction in heart rate (HR). Atrioventricular (AV) conduction delays, which were typically asymptomatic, were detected in a small minority of patients. We report the first-dose effects of fingolimod in patients who switched from injectable therapies during the Evaluate Patient OutComes (EPOC) study (ClinicalTrials.gov Identifier: NCT01216072). This was a phase 4, 6-month, randomized, active-comparator, open-label, multicenter study. It included over 900 fingolimod-treated patients with relapsing multiple sclerosis, with subgroups of individuals who were receiving common concomitant HR-lowering medications or had pre-existing cardiac conditions (PCCs). Vital signs were recorded hourly for 6h post-dose. A 12-lead electrocardiogram was obtained at baseline and at 6h post-dose. A transient decrease in mean HR and blood pressure occurred within 6h of the first fingolimod dose. The incidence of symptomatic bradycardia was low (1%); eight patients reported dizziness and there was one case each of fatigue, palpitations, dyspnea, cardiac discomfort, and gait disturbance. These symptomatic events were typically mild or moderate in severity and all resolved spontaneously, without intervention or fingolimod discontinuation. First-dose effects in patients with PCCs and in those receiving concomitant HR-lowering medications were consistent with effects observed in the overall study population and with results from previous clinical trials. The EPOC study provides additional data demonstrating the transient and generally benign nature of fingolimod first-dose effects on HR and AV conduction in a large population that is more representative of patients encountered in routine clinical practice than in the pivotal trials. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Phase 1, open-label study of MEDI-547 in patients with relapsed or refractory solid tumors.

    Science.gov (United States)

    Annunziata, Christina M; Kohn, Elise C; LoRusso, Patricia; Houston, Nicole D; Coleman, Robert L; Buzoianu, Manuela; Robbie, Gabriel; Lechleider, Robert

    2013-02-01

    Targeting the cell-surface receptor EphA2, which is highly expressed in some solid tumors, is a novel approach for cancer therapy. We aimed to evaluate the safety profile, maximum tolerated dose (MTD), pharmacokinetics, and antitumor activity of MEDI-547, an antibody drug conjugate composed of the cytotoxic drug auristatin (toxin) linked to a human anti-EphA2 monoclonal antibody (1C1), in patients with solid tumors relapsed/refractory to standard therapy. In this phase 1, open-label study with planned dose-escalation and dose-expansion cohorts, patients received a 1-h intravenous infusion of MEDI-547 (0.08 mg/kg) every 3 weeks. Six patients received 0.08 mg/kg; all discontinued treatment. Dose escalation was not pursued. The study was stopped before cohort 2 enrollment due to treatment-related bleeding and coagulation events (hemorrhage-related, n = 3; epistaxis, n = 2). Therefore, lower doses were not explored and an MTD could not be selected. The most frequently reported treatment-related adverse events (AEs) were increased liver enzymes, decreased hemoglobin, decreased appetite, and epistaxis. Three patients (50%) experienced treatment-related serious AEs, including conjunctival hemorrhage, pain (led to study drug discontinuation), liver disorder, and hemorrhage. Best response included progressive disease (n = 5; 83.3%) and stable disease (n = 1; 16.7%). Minimal or no dissociation of toxin from 1C1 conjugate occurred in the blood. Serum MEDI-547 concentrations decreased rapidly, ~70% by 3 days post-dose. No accumulation of MEDI-547 was observed at 0.08 mg/kg upon administration of a second dose 3 weeks following dose 1. The safety profile of MEDI-547 does not support further clinical investigation in patients with advanced solid tumors.

  9. Multicenter, prospective, open-label, observational study of bimatoprost 0.01% in patients with primary open-angle glaucoma or ocular hypertension

    Directory of Open Access Journals (Sweden)

    Laube T

    2012-05-01

    Full Text Available Stefan Pfennigsdorf,1 Osman Ramez,2 Gerrit von Kistowski,3 Birgit Mäder,4 Peter Eschstruth,5 Michael Froböse,6 Ulrich Thelen,7 Christoph Spraul,8 Dietmar Schnober,9 Hazel Cooper,10 Thomas Laube111Polch Ophthalmology Practice, Polch, 2Buxtehude Ophthalmology Practice, Buxtehude, 3Nürnberg Ophthalmology Practice, Nürnberg, 4Weißwasser Ophthalmology Practice, Weißwasser, 5Ophthalmology Practice, Kiel, 6Ophthalmology Practice, Bielefeld, 7Group Practice, Münster, 8Group Practice, Ulm, 9Ophthalmology Practice, Werdohl, Germany; 10Allergan, Marlow, UK, 11Group Practice, Düsseldorf, GermanyBackground: Bimatoprost 0.01% was developed for improved tolerability over bimatoprost 0.03%, while maintaining efficacy in lowering intraocular pressure (IOP. This multicenter, prospective, open-label, observational study was designed to investigate the efficacy and tolerability of bimatoprost 0.01% in routine clinical practice.Methods: Data were collected from 10,337 patients with primary open-angle glaucoma or ocular hypertension attending 1334 centers in Germany. The primary efficacy outcome was mean change in IOP in each eye from baseline to 10–14 weeks after initiation of bimatoprost 0.01%. Target IOP, prior therapies, additional treatments, and adverse events were also assessed. All treatment decisions were at the physicians’ discretion.Results: Bimatoprost 0.01% significantly lowered mean IOP from baseline by –4.1 mmHg (P < 0.0001 in all patients after a mean of 10.45 weeks. In patients without previous treatment, bimatoprost 0.01% reduced mean IOP from baseline by –6.5 mmHg (P < 0.0001. Bimatoprost 0.01% also significantly reduced IOP in patients previously treated with monotherapy of β-blockers, prostaglandin analogs, carbonic anhydrase inhibitors or bimatoprost 0.03%. No adverse events were reported by 93.9% of patients during treatment with bimatoprost 0.01%; the most commonly reported adverse events were eye irritation (2.0%, ocular

  10. Outcomes of switching directly to oral fingolimod from injectable therapies: Results of the randomized, open-label, multicenter, Evaluate Patient OutComes (EPOC) study in relapsing multiple sclerosis.

    Science.gov (United States)

    Fox, Edward; Edwards, Keith; Burch, Gordon; Wynn, Daniel R; LaGanke, Chris; Crayton, Heidi; Hunter, Samuel F; Huffman, Cynthia; Kim, Edward; Pestreich, Linda; McCague, Kevin; Barbato, Luigi

    2014-09-01

    The Evaluate Patient OutComes (ClinicalTrials.gov Identifier: NCT01216072) study was conducted in North America to assess patient- and physician-reported treatment satisfaction in patients with relapsing multiple sclerosis (MS) who received oral fingolimod for 6 months after switching from an injectable disease-modifying therapy (iDMT), without an intervening washout. In this open-label, multicenter study, patients were randomized 3:1 to once-daily fingolimod 0.5mg or iDMT. The primary study objective was to evaluate differences in satisfaction measured using the Treatment Satisfaction Questionnaire for Medication v1.4. Of 1053 patients randomized, 790 patients received fingolimod and 263 patients received iDMT. Treatment satisfaction improved significantly in patients who switched to fingolimod compared with those who continued iDMT. Patients also reported significant improvements in health-related quality of life, reduced depression, and reduced fatigue severity after a switch to fingolimod. No difference between the treatment groups was detected on the Patient Reported Indices for MS Activities scale. The safety profile of fingolimod was consistent with that reported in the pivotal phase 3 studies. The most commonly reported adverse events were more prevalent in patients who switched to fingolimod than in those who continued iDMT (headache: 12% vs 3%; fatigue: 12% vs 6%). No significant relationship between lymphocyte counts and infection rates was observed and there was no evidence of additive immune-system effects, which might be expected when switching to a different class of immunomodulatory therapy with no intervening washout. Patients who switched from iDMT to fingolimod had significant improvements in most self-reported outcomes compared with those who continued iDMT. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Effect of levitra on sustenance of erection (EROS): an open-label, prospective, multicenter, single-arm study to investigate erection duration measured by stopwatch with flexible dose vardenafil administered for 8 weeks in subjects with erectile dysfunction.

    Science.gov (United States)

    Shin, Y S; Lee, S W; Park, K; Chung, W S; Kim, S W; Hyun, J S; Moon, D G; Yang, S-K; Ryu, J K; Yang, D Y; Moon, K H; Min, K S; Park, J K

    2015-01-01

    To investigate the change of erection duration measured by stopwatch with flexible dose vardenafil administered for 8 weeks in subjects with erectile dysfunction (ED). Effect of levitra on sustenance of erection was an open-label, prospective, multicenter and single-arm study designed to measure the duration of erection in men with ED receiving a flexible dose of vardenafil over an 8-week treatment period. Patients were instructed to take vardenafil 10 mg 60 min before attempting the intercourse. Vardenfil could be increased to 20 mg or decreased to 5 mg concerning patients' efficacy and safety. Following the initial screening, patients entered a 4-week treatment-free run-in phase and 8-week treatment period, during which they were instructed to attempt intercourse at least four times on four separate days. A total of 95 men were enrolled in 10 centers. After the 8 weeks treatment, the mean duration of erection leading to successful intercourse was statistically superior when patients were treated with vardenafil. After an 8-week treatment, the duration of erection leading to successful intercourse was 9.39 min. There were significant benefits with vardenafil in all domains of International Index of Erectile Function. Secondary efficacy end points included success rate of penetration, maintaining erection, ejaculation and satisfaction were superior when patients were treated with vardenafil. There was a significant correlation between duration of erection with other sexual factors. Also partner's sexual satisfaction was increased with vardenafil. Most adverse events were mild or moderate in severity. Vardenafil was safe and well tolerated. Vardenafil therapy provided a statistically superior duration of erection leading to successful intercourse in men with ED with female partner.

  12. Control of Moderate-to-Severe Plaque Psoriasis with Efalizumab: 24-Week, Open-Label, Phase IIIb/IV Latin American Study Results

    OpenAIRE

    Stengel, Fernando M; Petri, Valeria [UNIFESP; Campbell, Gladys AM; Dorantes, Gladys Leon; López, Magdalina; Ricardo L. Galimberti; Valdez, Raúl P; de Arruda, Lucia F; Guerra, Mario Amaya; Chouela, Edgardo N; Licu, Daiana; ,

    2009-01-01

    Introduction Psoriasis is a debilitating, chronic inflammatory systemic disease affecting around 2% of the South American population. Biological therapies offer the possibility of long-term therapy with improved safety and efficacy. Methods We conducted a multicentre, open-label, single-arm, Phase IIIb/IV study of adult patients (18–75 years) with moderate-to-severe plaque psoriasis who were candidates for systemic therapy or phototherapy. Patients received efalizumab subcutaneously (1.0 mg/k...

  13. Diabetes-specific enteral nutrition formula in hyperglycemic, mechanically ventilated, critically ill patients: a prospective, open-label, blind-randomized, multicenter study

    OpenAIRE

    Mesejo, Alfonso; Montejo-González, Juan Carlos; Vaquerizo-Alonso, Clara; Lobo-Tamer, Gabriela; Zabarte-Martinez, Mercedes; Herrero-Meseguer, Jose Ignacio; Acosta-Escribano, Jose; Blesa-Malpica, Antonio; Martinez-Lozano, Fátima

    2015-01-01

    Introduction Although standard enteral nutrition is universally accepted, the use of disease-specific formulas for hyperglycemic patients is still controversial. This study examines whether a high-protein diabetes-specific formula reduces insulin needs, improves glycemic control and reduces ICU-acquired infection in critically ill, hyperglycemic patients on mechanical ventilation (MV). Methods This was a prospective, open-label, randomized (web-based, blinded) study conducted at nine Spanish ...

  14. Adjunctive levetiracetam in children, adolescents, and adults with primary generalized seizures: Open-label, noncomparative, multicenter, long-term follow-up study.

    LENUS (Irish Health Repository)

    Delanty, Norman

    2012-02-01

    Purpose: To evaluate the long-term efficacy and tolerability of adjunctive levetiracetam (LEV) in patients with uncontrolled idiopathic generalized epilepsy (IGE). Methods: This phase III, open-label, long-term, follow-up study (N167; NCT00150748) enrolled patients (4 to <65 years) with primary generalized seizures (tonic-clonic, myoclonic, absence). Patients received adjunctive LEV at individualized doses (1,000-4,000 mg\\/day; 20-80 mg\\/kg\\/day for children\\/adolescents weighing <50 kg). Efficacy results are reported for all seizure types [intention-to-treat (ITT) population, N = 217] and subpopulations with tonic-clonic (n = 152), myoclonic (n = 121), and\\/or absence (n = 70) seizures at baseline. Key Findings: One hundred twenty-five (57.6%) of 217 patients were still receiving treatment at the end of the study. Mean (standard deviation, SD) LEV dose was 2,917.5 (562.9) mg\\/day. Median (Q1-Q3) exposure to LEV was 2.1 (1.5-2.8) years, and the maximum duration was 4.6 years. Most patients were taking one (124\\/217, 57.1%) or >\\/=2 (92\\/217, 42.4%) concomitant antiepileptic drugs (AEDs). Seizure freedom of >\\/=6 months (all seizure types; primary efficacy end point) was achieved by 122 (56.2%) of 217 patients, and 49 (22.6%) of 217 patients had complete seizure freedom. Seizure freedom of >\\/=6 months from tonic-clonic, myoclonic, and absence seizures was achieved by 95 (62.5%) of 152, 75 (62.0%) of 121, and 44 (62.9%) of 70 patients, respectively. Mean (SD) maximum seizure freedom duration was 371.7 (352.4) days. At least one treatment-emergent adverse event (TEAE) was reported by 165 (76%) of 217 patients; most TEAEs were mild\\/moderate in severity, with no indication of an increased incidence over time. Seventeen (7.8%) of 217 patients discontinued medication because of TEAEs. The most common psychiatric TEAEs were depression (16\\/217, 7.4%), insomnia (9\\/217, 4.1%), nervousness (8\\/217, 3.7%), and anxiety (7\\/217, 3.2%). Significance: Adjunctive

  15. A combined phase I and II open label study on the effects of a seaweed extract nutrient complex on osteoarthritis

    Directory of Open Access Journals (Sweden)

    Stephen P Myers

    2010-02-01

    Full Text Available Stephen P Myers1,2, Joan O’Connor1,2, J Helen Fitton3, Lyndon Brooks4, Margaret Rolfe4, Paul Connellan5, Hans Wohlmuth2,5,6, Phil A Cheras1,2, Carol Morris51NatMed-Research, 2Centre for Health and Wellbeing, 4Graduate Research College, 5Centre for Phytochemistry and Pharmacology, 6Medicinal Plant Herbarium, Southern Cross University, Lismore, NSW, Australia; 3Marinova Pty Ltd, Hobart, Tasmania, AustraliaBackground: Isolated fucoidans from brown marine algae have been shown to have a range of anti-inflammatory effects.Purpose: This present study tested a Maritech® extract formulation, containing a blend of extracts from three different species of brown algae, plus nutrients in an open label combined phase I and II pilot scale study to determine both acute safety and efficacy in osteoarthritis of the knee. Patients and methods: Participants (n = 12, five females [mean age, 62 ± 11.06 years] and seven males [mean age, 57.14 ± 9.20 years] with a confirmed diagnosis of osteoarthritis of the knee were randomized to either 100 mg (n = 5 or 1000 mg (n = 7 of a Maritech® extract formulation per day. The formulation contained Maritech® seaweed extract containing Fucus vesiculosis (85% w/w, Macrocystis pyrifera (10% w/w and Laminaria japonica (5% w/w plus vitamin B6, zinc and manganese. Primary outcome was the average comprehensive arthritis test (COAT score which is comprised of four sub-scales: pain, stiffness, difficulty with physical activity and overall symptom severity measured weekly. Safety measures included full blood count, serum lipids, liver function tests, urea, creatinine and electrolytes determined at baseline and week 12. All adverse events were recorded.Results: Eleven participants completed 12 weeks and one completed 10 weeks of the study. Using a multilevel linear model, the average COAT score was reduced by 18% for the 100 mg treatment and 52% for the 1000 mg dose at the end of the study. There was a clear dose response effect

  16. Efficacy, tolerability and safety of switching from etanercept to infliximab for the treatment of moderate-to-severe psoriasis: A multicenter, open-label trial (TANGO).

    Science.gov (United States)

    Ayala, Fabio; Lambert, Julien

    2015-01-01

    Biologic anti-tumor necrosis factor-α (anti-TNF-α) therapies have revolutionized the management of psoriasis. However, despite similar mechanisms of action, inter-patient variability in the clinical responses to therapy remain unexplained. Possible differences between agents include stability or bioavailability and anti-drug antibody development, and patient factors such as compliance may play a role. As a result, it is not uncommon for physicians to switch a patient from one anti-TNF-α agent to another when initial response is inadequate. This multicenter, single-arm, observational, Phase IV study assessed the efficacy and safety of infliximab therapy in patients with moderate-to-severe psoriasis who had not responded to 24 weeks' etanercept treatment. Drug efficacy was assessed using specific psoriasis indexes; health-related quality of life (HRQoL) was measured using the Dermatology Life Quality Index and the Skindex-29. A total of 48 patients were screened, 38 were treated with infliximab and 31 completed the study. Of these, 71% achieved Psoriasis Area and Severity Index 75 after 10 weeks, and improvement in HRQoL was documented. The results of this study showed that patients with moderate-to-severe psoriasis could be successfully switched from etanercept to infliximab, with improvements in both clinical parameter and HRQoL.

  17. Two-year follow-up of an open-label multicenter study of polyacrylamide hydrogel (Bulkamid®) for female stress and stress-predominant mixed incontinence

    DEFF Research Database (Denmark)

    Toozs-Hobson, Philip; Al-Singary, Waleed; Fynes, Michelle

    2012-01-01

    Polyacrylamide hydrogel (PAHG, Bulkamid®) is a promising urethral bulking agent. This article presents the 2-year follow-up results of a multicenter study of PAHG injections for treating stress and stress-predominant mixed urinary incontinence....

  18. Comparison of the effectiveness and safety of cefpodoxime and ciprofloxacin in acute exacerbation of chronic suppurative otitis media: A randomized, open-labeled, phase IV clinical trial

    Directory of Open Access Journals (Sweden)

    Arijit Ghosh

    2012-01-01

    Full Text Available Objective : To compare the effectiveness and safety of cefpodoxime and ciprofloxacin for the treatment of mild to moderate cases of acute exacerbation of chronic suppurative otitis media (AECSOM. Materials and Methods : Adult patients diagnosed with AECSOM were screened and patients fulfilling the inclusion criteria were randomized to receive either cefpodoxime 200 mg twice daily or ciprofloxacin 500 mg twice daily orally for 7 days. The primary outcome of this randomized, open-labeled, phase IV clinical trial (Registration Number - CTRI/2011/10/002079 was clinical success rate at day 14 visit and the secondary outcome was incidence of adverse events (AEs. Forty-six patients were enrolled: 23 in the cefpodoxime group and 23 in the ciprofloxacin group. Results : The clinical success rates were 95.6% in the cefpodoxime group versus 90.9% in the ciprofloxacin group. These rates are comparable, but no statistically significant difference was observed between the groups. Few mild and self-limiting AEs were observed and the tolerability of both the drugs was also good. Conclusion : The results of this randomized, open-labeled phase IV clinical trial showed that a 7-day course of cefpodoxime is therapeutically comparable to ciprofloxacin in terms of both clinical effectiveness and safety for the treatment of patients with AECSOM.

  19. Safety and performance of cohesive polydensified matrix hyaluronic acid fillers with lidocaine in the clinical setting – an open-label, multicenter study

    Science.gov (United States)

    Kühne, Ulrich; Esmann, Jørgen; von Heimburg, Dennis; Imhof, Matthias; Weissenberger, Petra; Sattler, Gerhard

    2016-01-01

    Cohesive polydensified matrix (CPM®) hyaluronic acid fillers are now available with or without lidocaine. The aim of this study was to investigate the safety and performance of CPM® fillers with lidocaine in the clinical setting. In an open-label, prospective, postmarketing study, 108 patients from seven sites in Germany and Denmark were treated with one or more lidocaine-containing CPM® fillers. Performance was assessed using the Merz Aesthetics Scales® (MAS). Pain was rated on an 11-point visual analog scale. Patients’ and physicians’ satisfaction as well as adverse events were recorded. Improvements of ≥1-point on MAS immediately after and 17 days posttreatment were observed in ~90% of patients compared with baseline. All investigators assessed ejection force, product positioning, and performance as similar or superior to the respective nonlidocaine products. Overall, 94% of investigators were satisfied with the esthetic outcomes and were willing to continue using the products. All patients except one were satisfied with the results, and all were willing to repeat the treatment. Mean pain scores were low during (<3.0) and after injection (<0.6). Except for one case of bruising, all adverse events were mild to moderate. CPM® fillers with lidocaine are safe and effective for a wide range of esthetic facial indications. PMID:27799807

  20. An Open-Label, Multicenter Observational Study for Patients with Alzheimer’s Disease Treated with Memantine in the Clinical Practice

    Directory of Open Access Journals (Sweden)

    S.S. Stamouli

    2011-01-01

    Full Text Available Background/Aims: In this post-marketing observational study, the safety and effectiveness of memantine were evaluated in patients with Alzheimer’s disease (AD. Methods: In a 6-month, observational, open-label study at 202 specialist sites in Greece, the effectiveness of memantine was evaluated using the Mini-Mental State Examination (MMSE and the Instrumental Activities of Daily Living (IADL scale at baseline, and after 3 and 6 months. Discontinuation rates and adverse drug reactions (ADRs were also recorded to evaluate the safety profile of memantine. Results: 2,570 patients participated in the study. Three and 6 months after baseline, MMSE and IADL scores were significantly improved compared to baseline. At the end of the study, 67% of the patients had improved their MMSE score; 7.1% of the patients reported ≧1 ADRs, and treatment was discontinued due to ADR in 0.7%. Conclusion: Memantine was well tolerated and had a positive effect on the patient’s cognitive and functional ability in real-life clinical practice, in agreement with randomized, controlled trials.

  1. An Open Label, Phase 2 Study of MABp1 Monotherapy for the Treatment of Acne Vulgaris and Psychiatric Comorbidity.

    Science.gov (United States)

    Carrasco, Daniel; Stecher, Michael; Lefebvre, Gigi Claire; Logan, Alan C; Moy, Ronald

    2015-06-01

    Acne vulgaris is a common inflammatory skin disorder. There remain few rapid, safe, and effective therapy options for patients with moderate to severe acne vulgaris that also address psychological comorbidities such as anxiety. To assess the efficacy of interleukin 1 alpha blockade in patients with moderate to severe acne vulgaris using the true human monoclonal antibody MABp1. Eleven patients were administered open-label, subcutaneous injections of MABp1 over a six-week period. Objectives were assessment of safety, change in inflammatory lesion count and change in psychosocial functioning using two validated questionnaires. There were no serious adverse events, or adverse events greater than grade I. Median inflammatory lesion counts decreased 36% (IQR -44% to 1%). Anxiety scores improved (from median 6 to 1) as well as self-image assessment (2.3±0.9 to 2.1±0.1) as measured by the Hospital Anxiety and Depression Scale and the modified Body Image Disturbance Questionnaire. Patients had rapid improvement of skin lesions, as well as psychosocial functioning and anxiety. MABp1 may provide a safe and effective means for treating inflammatory acne lesions and. Further studies using this antibody are warranted in this patient population.

  2. Lamivudine switch therapy in chronic hepatitis B patients achieving undetectable hepatitis B virus DNA after 3 years of entecavir therapy: A prospective, open-label, multicenter study.

    Science.gov (United States)

    Yeh, Ming-Lun; Huang, Ching-I; Hsieh, Ming-Yen; Huang, Chung-Feng; Hsieh, Meng-Hsuan; Huang, Jee-Fu; Dai, Chia-Yen; Lin, Zu-Yau; Chen, Shinn-Chern; Yu, Ming-Lung; Chuang, Wan-Long

    2016-11-01

    The subsequent maintenance therapy in chronic hepatitis B (CHB) patients after long-term viral replication suppression is still uncertain. We aim to evaluate the efficacy of lamivudine (LAM) maintenance therapy in CHB patients achieving undetectable hepatitis B virus (HBV) DNA after 3 years of entecavir (ETV) therapy. Consecutive CHB patients who received at least 3 years of ETV and achieved HBV DNA negativity were allocated either LAM switch therapy or stopped ETV therapy in a prospective, open-label study. Another group of sex- and age-matched patients with continuous ETV therapy for at least 4 years served as historical control group. The primary outcome measurement of the study was relapse of HBV DNA (defined as serum HBV DNA level ≥ 2000 IU/mL). A total of 74 patients, including 42 of LAM switch and 32 of the nonswitch group, were enrolled. There were no significant differences in demographics, except a higher proportion of patients with positive hepatitis B envelope antigen in the nonswitch group at the initiation of ETV therapy. The LAM switch group had significantly lower 1-year relapse rate of HBV within 1 year compared to the nonswitch group (14.3% vs. 75%, p<0.001). However, none of the 48 historical control patients developed relapse of HBV, which was significantly lower than the rate in LAM switch group (p < 0.001). LAM switch was the only factor associated with HBV DNA relapse. In conclusion, continuous long-term potent nucleot(s)ide analogue therapy is mandatory for prevention of viral relapse in CHB patients. Copyright © 2016 Kaohsiung Medical University. Published by Elsevier Taiwan.. All rights reserved.

  3. Lamivudine switch therapy in chronic hepatitis B patients achieving undetectable hepatitis B virus DNA after 3 years of entecavir therapy: A prospective, open-label, multicenter study

    Directory of Open Access Journals (Sweden)

    Ming-Lun Yeh

    2016-11-01

    Full Text Available The subsequent maintenance therapy in chronic hepatitis B (CHB patients after long-term viral replication suppression is still uncertain. We aim to evaluate the efficacy of lamivudine (LAM maintenance therapy in CHB patients achieving undetectable hepatitis B virus (HBV DNA after 3 years of entecavir (ETV therapy. Consecutive CHB patients who received at least 3 years of ETV and achieved HBV DNA negativity were allocated either LAM switch therapy or stopped ETV therapy in a prospective, open-label study. Another group of sex- and age-matched patients with continuous ETV therapy for at least 4 years served as historical control group. The primary outcome measurement of the study was relapse of HBV DNA (defined as serum HBV DNA level ≥ 2000 IU/mL. A total of 74 patients, including 42 of LAM switch and 32 of the nonswitch group, were enrolled. There were no significant differences in demographics, except a higher proportion of patients with positive hepatitis B envelope antigen in the nonswitch group at the initiation of ETV therapy. The LAM switch group had significantly lower 1-year relapse rate of HBV within 1 year compared to the nonswitch group (14.3% vs. 75%, p < 0.001. However, none of the 48 historical control patients developed relapse of HBV, which was significantly lower than the rate in LAM switch group (p < 0.001. LAM switch was the only factor associated with HBV DNA relapse. In conclusion, continuous long-term potent nucleot(side analogue therapy is mandatory for prevention of viral relapse in CHB patients.

  4. Safety and performance of cohesive polydensified matrix hyaluronic acid fillers with lidocaine in the clinical setting – an open-label, multicenter study

    Directory of Open Access Journals (Sweden)

    Kühne U

    2016-10-01

    Full Text Available Ulrich Kühne,1 Jørgen Esmann,2 Dennis von Heimburg,3 Matthias Imhof,1 Petra Weissenberger,4 Gerhard Sattler,5 On behalf of the BALIA Study Group 1Aesthetische Dermatologie im Medico Palais, Bad Soden, Germany; 2Jørgen Esmann Aps, Hellerup, Denmark; 3Praxisklinik Kaiserplatz, Frankfurt am Main, Germany; 4Corporate Clinical Research, Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany; 5Rosenparkklinik GmbH, Darmstadt, Germany Abstract: Cohesive polydensified matrix (CPM® hyaluronic acid fillers are now available with or without lidocaine. The aim of this study was to investigate the safety and performance of CPM® fillers with lidocaine in the clinical setting. In an open-label, prospective, postmarketing study, 108 patients from seven sites in Germany and Denmark were treated with one or more lidocaine-containing CPM® fillers. Performance was assessed using the Merz Aesthetics Scales® (MAS. Pain was rated on an 11-point visual analog scale. Patients’ and physicians’ satisfaction as well as adverse events were recorded. Improvements of ≥1-point on MAS immediately after and 17 days posttreatment were observed in ~90% of patients compared with baseline. All investigators assessed ejection force, product positioning, and performance as similar or superior to the respective nonlidocaine products. Overall, 94% of investigators were satisfied with the esthetic outcomes and were willing to continue using the products. All patients except one were satisfied with the results, and all were willing to repeat the treatment. Mean pain scores were low during (<3.0 and after injection (<0.6. Except for one case of bruising, all adverse events were mild to moderate. CPM® fillers with lidocaine are safe and effective for a wide range of esthetic facial indications. Keywords: cohesive polydensified matrix, dermal fillers, Belotero, Esthélis, Fortélis, Modélis

  5. Intravenous azithromycin plus ceftriaxone followed by oral azithromycin for the treatment of inpatients with community-acquired pneumonia: an open-label, non-comparative multicenter trial

    Directory of Open Access Journals (Sweden)

    Fernando G. Rubio

    Full Text Available Community-Acquired Pneumonia (CAP is a major public health problem. In Brazil it has been estimated that 2,000,000 people are affected by CAP every year. Of those, 780,000 are admitted to hospital, and 30,000 have death as the outcome. This is an open-label, non-comparative study with the purpose of evaluating efficacy, safety, and tolerability levels of IV azithromycin (IVA and IV ceftriaxone (IVC, followed by oral azithromycin (OA for the treatment of inpatients with mild to severe CAP. Eighty-six patients (mean age 56.6 ± 19.8 were administered IVA (500mg/day and IVC (1g/day for 2 to 5 days, followed by AO (500mg/day to complete a total of 10 days. At the end of treatment (EOT and after 30 days (End of Study - EOS the medication was evaluated clinically, microbiologically and for tolerability levels. Out of the total 86-patient population, 62 (72.1% completed the study. At the end of treatment, 95.2% (CI95: 88.9% - 100% reported cure or clinical improvement; at the end of the study, that figure was 88.9% (CI95: 74.1% - 91.7%. Out of the 86 patients enrolled in the study, 15 were microbiologically evaluable for bacteriological response. Of those, 6 reported pathogen eradication at the end of therapy (40%, and 8 reported presumed eradication (53.3%. At end of study evaluation, 9 patients showed pathogen eradication (50%, and 7 showed presumed eradication (38.89%. Therefore, negative cultures were obtained from 93.3% of the patients at EOT, and from 88.9% at the end of the study. One patient (6.67% of patient population reported presumed microbiological resistance. At study end, 2 patients (11.11% still reported undetermined culture. Uncontrollable vomiting and worsening pneumonia condition were reported by 2.3% of patients. Discussion and Conclusion Treatment based on the administration of IV azithromycin associated to ceftriaxone and followed by oral azithromycin proved to be efficacious and well-tolerated in the treatment of Brazilian

  6. A 16-Week Open-Label, Multicenter Pilot Study Assessing Insulin Pump Therapy in Patients with Type 2 Diabetes Suboptimally Controlled with Multiple Daily Injections

    Science.gov (United States)

    Frias, Juan P; Bode, Bruce W; Bailey, Timothy S; Kipnes, Mark S; Brunelle, Rocco; Edelman, Steven V

    2011-01-01

    Background We assessed the efficacy, safety, and patient-reported outcomes (PROs) of insulin pump therapy in patients with type 2 diabetes mellitus (T2DM) who were suboptimally controlled with a multiple daily injection (MDI) regimen. Methods In this subanalysis of a 16-week multicenter study, 21 insulin-pump-naïve patients [age 57 ± 13 years, hemoglobin A1c (A1C) 8.4 ± 1.0%, body weight 98 ± 20 kg, total daily insulin dose 99 ± 65 U, mean ± standard deviation] treated at baseline with MDI therapy with or without oral antidiabetic agents discontinued all diabetes medications except metformin and initiated insulin pump therapy. Insulin was titrated to achieve the best possible glycemic control with the simplest possible dosing regimen. Outcome measures included A1C, fasting and postprandial glucose, body weight, incidence of hypoglycemia, and PROs. Results Glycemic control improved significantly after 16 weeks: A1C 7.3 ± 1.0% (−1.1 ± 1.2%, p insulin doses were 66 ± 36, 56 ± 40, and 122 ± 72 U (1.2 U/kg), respectively, and 90% of patients were treated with two or fewer daily basal rates. Body weight increased by 2.8 ± 2.6 kg (p Insulin pump therapy using a relatively simple dosing regimen safely improved glucose control and PROs in patients with T2DM who were unable to achieve glycemic targets with MDI therapy. Controlled trials are needed to further assess the clinical benefits and cost-effectiveness of insulin pumps in this patient population. PMID:21880230

  7. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial

    DEFF Research Database (Denmark)

    Choueiri, Toni K; Escudier, Bernard; Powles, Thomas

    2016-01-01

    BACKGROUND: Cabozantinib is an oral inhibitor of tyrosine kinases including MET, VEGFR, and AXL. The randomised phase 3 METEOR trial compared the efficacy and safety of cabozantinib versus the mTOR inhibitor everolimus in patients with advanced renal cell carcinoma who progressed after previous V...

  8. A multinational, open-label, phase 2 study of ruxolitinib in Asian patients with myelofibrosis: Japanese subset analysis.

    Science.gov (United States)

    Oritani, Kenji; Okamoto, Shinichiro; Tauchi, Tetsuzo; Saito, Shigeki; Ohishi, Kohshi; Handa, Hiroshi; Takenaka, Katsuto; Gopalakrishna, Prashanth; Amagasaki, Taro; Ito, Kazuo; Akashi, Koichi

    2015-03-01

    Ruxolitinib is a potent Janus kinase (JAK) 1/JAK2 inhibitor that has demonstrated rapid and durable improvements in splenomegaly and symptoms and a survival benefit in 2 phase 3 trials in patients with myelofibrosis. Ruxolitinib was well tolerated and effectively reduced splenomegaly and symptom burden in Asian patients with myelofibrosis in the Asian multinational, phase 2 Study A2202. We present a subset analysis of Japanese patients (n = 30) in Study A2202. At data cutoff, 22 patients were ongoing; 8 discontinued, mainly due to adverse events (n = 4). At week 24, 33 % of patients achieved ≥35 % reduction from baseline in spleen volume; 56.0 % achieved ≥50 % reduction from baseline in total symptom score, as measured by the 7-day Myelofibrosis Symptom Assessment Form v2.0. The most common adverse events were anemia (63 %), thrombocytopenia (40 %), nasopharyngitis (37 %), decreased platelet counts (30 %), and diarrhea (30 %). Dose reductions or interruptions due to hemoglobin decreases were more frequent in Japanese patients; no loss of efficacy and no discontinuations due to hematologic abnormalities were observed. Ruxolitinib was well tolerated in Japanese patients and provided substantial reductions in splenomegaly and myelofibrosis-related symptoms similar to those observed in the overall Asian population and phase 3 COMFORT studies.

  9. Control of Moderate-to-Severe Plaque Psoriasis with Efalizumab: 24-Week, Open-Label, Phase IIIb/IV Latin American Study Results

    Science.gov (United States)

    Stengel, Fernando M; Petri, Valeria; Campbell, Gladys AM; Dorantes, Gladys Leon; López, Magdalina; Galimberti, Ricardo L; Valdez, Raúl P; de Arruda, Lucia F; Guerra, Mario Amaya; Chouela, Edgardo N; Licu, Daiana

    2009-01-01

    Introduction Psoriasis is a debilitating, chronic inflammatory systemic disease affecting around 2% of the South American population. Biological therapies offer the possibility of long-term therapy with improved safety and efficacy. Methods We conducted a multicentre, open-label, single-arm, Phase IIIb/IV study of adult patients (18–75 years) with moderate-to-severe plaque psoriasis who were candidates for systemic therapy or phototherapy. Patients received efalizumab subcutaneously (1.0 mg/kg/wk). The primary endpoint was the proportion of patients achieving a Physician Global Assessment (PGA) rating of “excellent” or “cleared” at Week 24. Safety outcomes were adverse events (AEs), serious AEs (SAEs) and abnormalities on laboratory tests. Results Of 189 patients included in the intent-to-treat and safety populations, 104 (55.0%) were of Hispanic or Latino ethnicity. At Week 24, 92/189 (48.7%) patients achieved or maintained a PGA rating of “excellent” or “cleared”. AEs were reported by 161/189 (85.2%) patients, SAEs by 21/189 (11.1%). One patient died during the study (meningoencephalitis). Laboratory findings were consistent with previous experience. Conclusions Efalizumab demonstrated sustained control of psoriasis up to 24 weeks in patients from Latin America, confirming results seen in Phase III studies conducted in North America and Europe. PMID:20098510

  10. A phase II Open-label Study of the Intravenous Administration of Homoharringtonine in the treatment of Myelodysplastic syndrome

    Science.gov (United States)

    Daver, Naval; Vega-Ruiz, Arturo; Kantarjian, Hagop M.; Estrov, Zeev; Ferrajoli, Alessandra; Kornblau, Steve; Verstovsek, Srdan; Garcia-Manero, Guillermo; Cortes, Jorge E.

    2013-01-01

    Homoharringtonine is an alkaloid inhibitor of protein synthesis with activity in myeloid malignancies. We report a phase II pilot study of homoharringtonine in myelodysplastic syndrome (MDS). Induction consisted of homoharringtonine at 2.5 mg/m2 via continuous infusion for seven days. Maintenance was given every 4 weeks. Nine patients were enrolled: five with refractory anaemia with excess blasts, two with refractory anaemia with excess blasts in transformation, one each with refractory anaemia and chronic myelomonocytic leukaemia, respectively. Median age was 70 years (55–84) and 6 (66%) were male. Per International Prognostic Scoring System (IPSS) two patients were intermediate-1, five intermediate-2 and two high-risk. Median chemotherapy courses were one (1–3). One patient (11%) responded with complete hematologic and cytogenetic remission after one course. Eight patients did not respond (four had stable disease, two progressed to acute leukaemia and two died during induction - from aspergillus pneumonia and intracerebral haemorrhage, respectively). Grade 3/4 myelosuppression seen in 56% (5/9). Serious non-hematologic toxicities included one case of grade 4 left bundle branch heart block and one grade 3 nephrotoxicity. Median time between courses was 42 days (35–72 days). In conclusion homoharringtonine might have clinical activity in some patients with MDS. PMID:23701251

  11. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial.

    Science.gov (United States)

    Pujade-Lauraine, Eric; Hilpert, Felix; Weber, Béatrice; Reuss, Alexander; Poveda, Andres; Kristensen, Gunnar; Sorio, Roberto; Vergote, Ignace; Witteveen, Petronella; Bamias, Aristotelis; Pereira, Deolinda; Wimberger, Pauline; Oaknin, Ana; Mirza, Mansoor Raza; Follana, Philippe; Bollag, David; Ray-Coquard, Isabelle

    2014-05-01

    In platinum-resistant ovarian cancer (OC), single-agent chemotherapy is standard. Bevacizumab is active alone and in combination. AURELIA is the first randomized phase III trial to our knowledge combining bevacizumab with chemotherapy in platinum-resistant OC. Eligible patients had measurable/assessable OC that had progressed two prior anticancer regimens were ineligible. After investigators selected chemotherapy (pegylated liposomal doxorubicin, weekly paclitaxel, or topotecan), patients were randomly assigned to single-agent chemotherapy alone or with bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until progression, unacceptable toxicity, or consent withdrawal. Crossover to single-agent bevacizumab was permitted after progression with chemotherapy alone. The primary end point was progression-free survival (PFS) by RECIST. Secondary end points included objective response rate (ORR), overall survival (OS), safety, and patient-reported outcomes. The PFS hazard ratio (HR) after PFS events in 301 of 361 patients was 0.48 (95% CI, 0.38 to 0.60; unstratified log-rank P < .001). Median PFS was 3.4 months with chemotherapy alone versus 6.7 months with bevacizumab-containing therapy. RECIST ORR was 11.8% versus 27.3%, respectively (P = .001). The OS HR was 0.85 (95% CI, 0.66 to 1.08; P < .174; median OS, 13.3 v 16.6 months, respectively). Grade ≥ 2 hypertension and proteinuria were more common with bevacizumab. GI perforation occurred in 2.2% of bevacizumab-treated patients. Adding bevacizumab to chemotherapy statistically significantly improved PFS and ORR; the OS trend was not significant. No new safety signals were observed.

  12. Robot-assisted Versus Laparoscopic Surgery for Rectal Cancer: A Phase II Open Label Prospective Randomized Controlled Trial.

    Science.gov (United States)

    Kim, Min Jung; Park, Sung Chan; Park, Ji Won; Chang, Hee Jin; Kim, Dae Yong; Nam, Byung-Ho; Sohn, Dae Kyung; Oh, Jae Hwan

    2017-05-25

    The phase II randomized controlled trial aimed to compare the outcomes of robot-assisted surgery with those of laparoscopic surgery in the patients with rectal cancer. The feasibility of robot-assisted surgery over laparoscopic surgery for rectal cancer has not been established yet. Between February 21, 2012 and March 11, 2015, patients with rectal cancer (cT1-3NxM0) were enrolled. Patients were randomized 1:1 to either robot-assisted or laparoscopic surgery, and stratified per sex and administration of preoperative chemoradiotherapy. The primary outcome was the quality of total mesorectal excision (TME) specimen. Secondary outcomes were the circumferential and distal resection margins, the number of harvested lymph nodes, morbidity, bowel function recovery, and quality of life. A total of 163 patients were randomly assigned to the robot-assisted (n = 81) and laparoscopic (n = 82) surgery groups, and 139 patients were eligible for the analyses (73 vs 66, respectively). One patient (1.2%) in the robot-assisted group was converted to open surgery. The TME quality did not differ between the robot-assisted and laparoscopic groups (80.3% vs 78.1% complete TME, respectively; 18.2% vs 21.9% nearly complete TME, respectively; P = 0.599). The resection margins, number of harvested lymph nodes, morbidity, and bowel function recovery also were not significantly different. On analyzing quality of life, scores of the European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLQ C30) and EORTC QLQ CR38 were similar in the 2 groups, but in the EORTC QLQ CR 38 questionnaire, sexual function 12 months postoperatively was better in the robot-assisted group than in the laparoscopic group (P = 0.03). Robot-assisted surgery in rectal cancer showed TME quality comparable with that of laparoscopic surgery, and it demonstrated similar postoperative morbidity, bowel function recovery, and quality of life.

  13. A randomized, open-label, multicenter study of the efficacy and safety of intravesical hyaluronic acid and chondroitin sulfate versus dimethyl sulfoxide in women with bladder pain syndrome/interstitial cystitis.

    Science.gov (United States)

    Cervigni, Mauro; Sommariva, Monica; Tenaglia, Raffaele; Porru, Daniele; Ostardo, Edoardo; Giammò, Alessandro; Trevisan, Silvia; Frangione, Valeria; Ciani, Oriana; Tarricone, Rosanna; Pappagallo, Giovanni L

    2017-04-01

    Intravesical instillation of hyaluronic acid (HA) plus chondroitin sulfate (CS) in women with bladder pain syndrome/interstitial cystitis (BPS/IC) has shown promising results. This study compared the efficacy, safety, and costs of intravesical HA/CS (Ialuril(®) , IBSA) to dimethyl sulfoxide (DMSO). Randomized, open-label, multicenter study involving 110 women with BPS/IC. The allocation ratio (HA/CS:DMSO) was 2:1. Thirteen weekly instillations of HA (1.6%)/CS (2.0%) or 50% DMSO were given. Patients were evaluated at 3 (end-of-treatment) and 6 months. Primary endpoint was reduction in pain intensity at 6 months by visual analogue scale (VAS) versus baseline. Secondary efficacy measurements were quality of life and economic analyses. A significant reduction in pain intensity was observed at 6 months in both treatment groups versus baseline (P DMSO for the per-protocol population (mean VAS reduction 44.77 ± 25.07 vs. 28.89 ± 31.14, respectively; P = 0.0186). There were no significant differences between treatment groups in secondary outcomes. At least one adverse event was reported in 14.86% and 30.56% of patients in the HA/CS and DMSO groups, respectively. There were significantly fewer treatment-related adverse events for HA/CS versus DMSO (1.35% vs. 22.22%; P = 0.001). Considering direct healthcare costs, the incremental cost-effectiveness ratio of HA/CS versus DMSO fell between 3735€/quality-adjusted life years (QALY) and 8003€/QALY. Treatment with HA/CS appears to be as effective as DMSO with a potentially more favorable safety profile. Both treatments increased health-related quality of life, while HA/CS showed a more acceptable cost-effectiveness profile. © 2016 Wiley Periodicals, Inc.

  14. An uncontrolled open-label, multicenter study to monitor the antiviral activity and safety of inhaled zanamivir (as Rotadisk via Diskhaler device) among Chinese adolescents and adults with influenza-like illness

    Institute of Scientific and Technical Information of China (English)

    CAO Bin; XU Qian; HU Ke; CHEN Bai-yi; YU Yun-song; SONG Shu-fan; SHU Yue-long; WANG Chen; WANG Da-yan; YU Xiao-min; WEI Lu-qing; PU Zeng-hui; GAO Yan; WANG Jing; DONG Jian-ping; LI Xiao-ling

    2012-01-01

    Background It is the first multicenter clinical study in China to investigate zanamivir use among Chinese adolescents and adults with influenza-like illness (ILI) since 2009,when inhaled zanamivir (RELENZA(R)) was marketed in China.Methods An uncontrolled open-label,multicentre study to evaluate the antiviral activity,and safety of inhaled zanamivir (as Rotadisk via Diskhaler device); 10 mg administered twice daily for 5 days in subjects ≥12 years old with ILl.Patients were enrolled within 48 hours of onset and followed for eight days.Patients were defined as being influenza-positive if the real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) test had positive results.Results A total of 400 patients ≥12 years old were screened from 11 centers in seven provinces from March 2010 to January 2011.Three hundred and ninety-two patients who took at least one dose of zanamivir were entered into the safety analysis.The mean age was 33.8 years and 50% were male.Cardiovascular diseases and diabetes were the most common comorbidities.All the reported adverse events,such as rash,nasal ache,muscle ache,nausea,diarrhea,headache,occurred in less than 1% of subjects.Mild sinus bradycadia or arrhythmia occurred in four subjects (1%).Most of the adverse events were mild and did not require any change of treatment.No severe adverse events (SAE) or fatal cases were reported.Bronchospasm was found in a 38 years old woman whose symptoms disappeared after stopping zanamivir and without additional treatment.All the 61 influenza virus isolates (43 before enrollment,18 during treatment) proved to be sensitive to zanamivir.Conclusions Zanamivir is well tolerated by Chinese adolescents and adults with ILls.There is no evidence for the emergence of drug-resistant isolates during treatment with zanamivir.(ChiCTR-TNRC-10000938)

  15. Hepatic Cyst Infection During Use of the Somatostatin Analog Lanreotide in Autosomal Dominant Polycystic Kidney Disease: An Interim Analysis of the Randomized Open-Label Multicenter DIPAK-1 Study.

    Science.gov (United States)

    Lantinga, Marten A; D'Agnolo, Hedwig M A; Casteleijn, Niek F; de Fijter, Johan W; Meijer, Esther; Messchendorp, Annemarie L; Peters, Dorien J M; Salih, Mahdi; Spithoven, Edwin M; Soonawala, Darius; Visser, Folkert W; Wetzels, Jack F M; Zietse, Robert; Drenth, Joost P H; Gansevoort, Ron T

    2017-02-01

    The DIPAK-1 Study investigates the reno- and hepatoprotective efficacy of the somatostatin analog lanreotide compared with standard care in patients with later stage autosomal dominant polycystic kidney disease (ADPKD). During this trial, we witnessed several episodes of hepatic cyst infection, all during lanreotide treatment. We describe these events and provide a review of the literature. The DIPAK-1 Study is an ongoing investigator-driven, randomized, controlled, open-label multicenter trial. Patients (ADPKD, ages 18-60 years, estimated glomerular filtration rate 30-60 mL/min/1.73 m(2)) were randomized 1:1 to receive lanreotide 120 mg subcutaneously every 28 days or standard care during 120 weeks. Hepatic cyst infection was diagnosed by local physicians. We included 309 ADPKD patients of which seven (median age 53 years [interquartile range: 48-55], 71% female, median estimated glomerular filtration rate 42 mL/min/1.73 m(2) [interquartile range: 41-58]) developed eight episodes of hepatic cyst infection during 342 patient-years of lanreotide use (0.23 cases per 10 patient-years). These events were limited to patients receiving lanreotide (p < 0.001 vs. standard care). Baseline characteristics were similar between subjects who did or did not develop a hepatic cyst infection during lanreotide use, except for a history of hepatic cyst infection (29 vs. 0.7%, p < 0.001). Previous studies with somatostatin analogs reported cyst infections, but did not identify a causal relationship. These data suggest an increased risk for hepatic cyst infection during use of somatostatin analogs, especially in ADPKD patients with a history of hepatic cyst infection. The main results are still awaited to fully appreciate the risk-benefit ratio. CLINICALTRIALS. NCT 01616927.

  16. An open label, randomized, comparative, parallel group, multicenter, prospective, interventional, clinical study to evaluate efficacy and safety of “AHPL/AYTOP/0113” in comparison with “Framycetin sulphate cream” in acute wounds

    Directory of Open Access Journals (Sweden)

    Sanjay U Nipanikar

    2017-01-01

    Full Text Available Objectives: The main objective of the present study was to assess efficacy and safety of AHPL/AYTOP/0113 cream, a polyherbal formulation in comparison with Framycetin sulphate cream in acute wounds. Methodology: It was an open label, randomized, comparative, parallel group and multi-center clinical study. Total 47 subjects were randomly assigned to Group-A (AHPL/AYTOP/0113 cream and 42 subjects were randomly assigned to Group-B (Framycetin sulphate cream. All the subjects were advised to apply study drug, thrice daily for 21 days or up to complete wound healing (whichever was earlier. All the subjects were called for follow up on days 2, 4, 7, 10, 14, 17 and 21 or up to the day of complete wound healing. Data describing quantitative measures are expressed as mean ± SD. Comparison of variables representing categorical data was performed using Chi-square test. Results: Group-A subjects took significantly less (P < 0.05 i.e., (mean 7.77 days than (mean 9.87 days of Group-B subjects for wound healing. At the end of the study, statistically significant better (P < 0.05 results were observed in Group-A than Group-B in mean wound surface area, wound healing parameters and pain associated with wound. Excellent overall efficacy and tolerability was observed in subjects of both the groups. No adverse event or adverse drug reaction was noted in any subject of both the groups. Conclusion: AHPL/AYTOP/0113 cream proved to be superior to Framycetin sulphate cream in healing of acute wounds.

  17. Recombinant fusion ESAT6-CFP10 immunogen as a skin test reagent for tuberculosis diagnosis: an open-label, randomized, two-centre phase 2a clinical trial.

    Science.gov (United States)

    Li, F; Xu, M; Qin, C; Xia, L; Xiong, Y; Xi, X; Fan, X; Gu, J; Pu, J; Wu, Q; Lu, S; Wang, G

    2016-10-01

    We sought to assess the accuracy and safety of the ESAT6-CFP10 reagent in diagnosing tuberculosis (TB) disease. An open-label, randomized phase 2a trial was conducted in 56 healthy adults and 88 TB patients at one medical centre and one teaching hospital in China. All participants received 0.1, 0.5, 1 or 2 μg ESAT6-CFP10 in their right forearm. Moreover, 56 healthy volunteers and 56 patients were given tuberculin-purified protein derivative (TB-PPD) in their left forearm. The remaining 32 patients were administered placebo. The main outcome measure was induration diameter. An enzyme-linked immunospot (ELISPOT) assay was conducted before the skin test. The ESAT6-CFP10 test caused a higher positivity rate than placebo (81.2% (26/32) vs. 3.1% (1/32); p skin test appears to be a safe and promising tool; further testing will confirm its efficacy in identifying TB disease. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  18. An open label phase II study evaluating first-line EGFR tyrosine kinase inhibitor erlotinib in non-small cell lung cancer patients with tumors showing high EGFR gene copy number

    Science.gov (United States)

    Kowalczyk, Anna; Suszko-Kazarnowicz, Malgorzata; Duchnowska, Renata; Szczesna, Aleksandra; Ratajska, Magdalena; Sowa, Aleksander; Limon, Janusz; Biernat, Wojciech; Burzykowski, Tomasz; Jassem, Jacek; Dziadziuszko, Rafal

    2017-01-01

    Background First-line treatment with epidermal growth factor receptor (EGFR) inhibitors in NSCLC is effective in patients with activating EGFR mutations. The activity of erlotinib in patients harboring high EGFR gene copy number has been considered debatable. Patients and Methods A multicenter, open-label, single-arm phase II clinical trial was performed to test the efficacy of erlotinib in the first-line treatment of NSCLC patients harboring high EGFR gene copy number defined as =4 copies in =40% of cells. Findings Between December 2007 and April 2011, tumor samples from 149 subjects were screened for EGFR gene copy number by fluorescence in-situ hybridization (FISH), Out of 49 patients with positive EGFR FISH test, 45 were treated with erlotinib. Median PFS in the intent-to-treat population was 3.3 months (95%CI: 1.83.9 months), and median overall survival was 7.9 months (95% CI: 5.112.6 months). Toxicity profile of erlotinib was consistent with its known safety profile. The trial was stopped prematurely at 63% of originally planned sample size due to accumulating evidence that EGFR gene copy number should not be used to select NSCLC patients to first-line therapy with EGFR TKI. Data on erlotinib efficacy according to EGFR, KRAS and BRAF mutations are additionally presented. Interpretation This trial argues against using high gene copy number for selection of NSCLC patients to first-line therapy with EGFR TKIs. The study adds to the discussion on efficacy of other targeted agents in patients with target gene amplified tumors. PMID:27924059

  19. Canakinumab treatment for patients with active recurrent or chronic TNF receptor-associated periodic syndrome (TRAPS): an open-label, phase II study

    Science.gov (United States)

    Gattorno, Marco; Obici, Laura; Cattalini, Marco; Tormey, Vincent; Abrams, Ken; Davis, Nicole; Speziale, Antonio; Bhansali, Suraj G; Martini, Alberto; Lachmann, Helen J

    2017-01-01

    Objective To evaluate the efficacy of canakinumab, a high-affinity human monoclonal anti-interleukin-1β antibody, in inducing complete or almost complete responses in patients with active tumour necrosis factor receptor-associated periodic syndrome (TRAPS). Methods Twenty patients (aged 7–78 years) with active recurrent or chronic TRAPS were treated with canakinumab 150 mg every 4 weeks for 4 months (2 mg/kg for those ≤40 kg) in this open-label, proof-of-concept, phase II study. Canakinumab was then withdrawn for up to 5 months, with reintroduction on relapse, and 4 weekly administration (subsequently increased to every 8 weeks) for 24 months. The primary efficacy variable was the proportion of patients achieving complete or almost complete response at day 15, defined as clinical remission (Physician's Global Assessment score ≤1) and full or partial serological remission. Results Nineteen patients (19/20, 95%; 95% CI 75.1% to 99.9%) achieved the primary efficacy variable. Responses to canakinumab occurred rapidly; median time to clinical remission 4 days (95% CI 3 to 8 days). All patients relapsed after canakinumab was withdrawn; median time to relapse 91.5 days (95% CI 65 to 117 days). On reintroduction of canakinumab, clinical and serological responses were similar to those seen during the first phase, and were sustained throughout treatment. Canakinumab was well tolerated and clinical responses were accompanied by rapid and sustained improvement in health-related quality of life. Weight normalised pharmacokinetics of canakinumab, although limited, appeared to be consistent with historical canakinumab data. Conclusions Canakinumab induces rapid disease control in patients with active TRAPS, and clinical benefits are sustained during long-term treatment. Trial registration number NCT01242813; Results. PMID:27269295

  20. An open-label, two-stage, phase II study of bevacizumab and lapatinib in children with recurrent or refractory ependymoma: a collaborative ependymoma research network study (CERN).

    Science.gov (United States)

    DeWire, Mariko; Fouladi, Maryam; Turner, David C; Wetmore, Cynthia; Hawkins, Cynthia; Jacobs, Carmen; Yuan, Ying; Liu, Diane; Goldman, Stewart; Fisher, Paul; Rytting, Michael; Bouffet, Eric; Khakoo, Yasmin; Hwang, Eugene I; Foreman, Nicholas; Stewart, Clinton F; Gilbert, Mark R; Gilbertson, Richard; Gajjar, Amar

    2015-05-01

    Co-expression of ERBB2 and ERBB4, reported in 75% of pediatric ependymomas, correlates with worse overall survival. Lapatinib, a selective ERBB1 and ERBB2 inhibitor has produced prolonged disease stabilization in patients with ependymoma in a phase I study. Bevacizumab exposure in ependymoma xenografts leads to ablation of tumor self-renewing cells, arresting growth. Thus, we conducted an open-label, phase II study of bevacizumab and lapatinib in children with recurrent ependymomas. Patients ≤ 21 years of age with recurrent ependymoma received lapatinib orally twice daily (900 mg/m(2)/dose to the first 10 patients, and then 700 mg/m(2)/dose) and bevacizumab 10 mg/kg intravenously on days 1 and 15 of a 28-day course. Lapatinib serum trough levels were analyzed prior to each course. Total and phosphorylated VEGFR2 expression was measured in peripheral blood mononuclear cells (PBMCs) before doses 1 and 2 of bevacizumab and 24-48 h following dose 2 of bevacizumab. Twenty-four patients with a median age of 10 years (range 2-21 years) were enrolled; 22 were eligible and 20 evaluable for response. Thirteen had anaplastic ependymoma. There were no objective responses; 4 patients had stable disease for ≥ 4 courses (range 4-14). Grade 3 toxicities included rash, elevated ALT, and diarrhea. Grade 4 toxicities included peri-tracheostomy hemorrhage (n = 1) and elevated creatinine phosphokinase (n = 1). The median lapatinib pre-dose trough concentration was 3.72 µM. Although the combination of bevacizumab and lapatinib was well tolerated in children with recurrent ependymoma, it proved ineffective.

  1. Impact of elosulfase alfa in patients with morquio A syndrome who have limited ambulation: An open-label, phase 2 study.

    Science.gov (United States)

    Harmatz, Paul R; Mengel, Eugen; Geberhiwot, Tarekegn; Muschol, Nicole; Hendriksz, Christian J; Burton, Barbara K; Jameson, Elisabeth; Berger, Kenneth I; Jester, Andrea; Treadwell, Marsha; Sisic, Zlatko; Decker, Celeste

    2017-02-01

    Efficacy and safety of elosulfase alfa enzyme replacement therapy (ERT) were assessed in an open-label, phase 2, multi-national study in Morquio A patients aged ≥5 years unable to walk ≥30 meters in the 6-min walk test. Patients received elosulfase alfa 2.0 mg/kg/week intravenously for 48 weeks. Efficacy measures were functional dexterity, pinch/grip strength, mobility in a modified timed 25-foot walk, pain, quality of life, respiratory function, and urine keratan sulfate (KS). Safety/tolerability was also assessed. Fifteen patients received elosulfase alfa, three patients discontinued ERT due to adverse events (two were grade 3 drug-related adverse events, the other was not drug-related), and two patients missed >20% of planned infusions; 10 completed treatment through 48 weeks and received ≥80% of planned infusions (Modified Per Protocol [MPP] population). The study population had more advanced disease than that enrolled in other trials. From baseline to week 48, MPP data showed biochemical efficacy (urine KS decreased 52.4%). The remaining efficacy results were highly variable due to challenges in test execution because of severe skeletal and joint abnormalities, small sample sizes, and clinical heterogeneity among patients. Eight patients showed improvements in one or more outcome measures; several patients indicated improvements not captured by the study assessments (e.g., increased energy, functional ability). The nature of adverse events was similar to other elosulfase alfa studies. This study illustrates the considerable challenges in objectively measuring impact of ERT in very disabled Morquio A patients and highlights the need to examine results on an individual basis. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.

  2. Primary analysis of a phase II open-label trial of INCB039110, a selective JAK1 inhibitor, in patients with myelofibrosis

    Science.gov (United States)

    Mascarenhas, John O.; Talpaz, Moshe; Gupta, Vikas; Foltz, Lynda M.; Savona, Michael R.; Paquette, Ronald; Turner, A. Robert; Coughlin, Paul; Winton, Elliott; Burn, Timothy C.; O’Neill, Peter; Clark, Jason; Hunter, Deborah; Assad, Albert; Hoffman, Ronald; Verstovsek, Srdan

    2017-01-01

    Combined Janus kinase 1 (JAK1) and JAK2 inhibition therapy effectively reduces splenomegaly and symptom burden related to myelofibrosis but is associated with dose-dependent anemia and thrombocytopenia. In this open-label phase II study, we evaluated the efficacy and safety of three dose levels of INCB039110, a potent and selective oral JAK1 inhibitor, in patients with intermediate- or high-risk myelofibrosis and a platelet count ≥50×109/L. Of 10, 45, and 32 patients enrolled in the 100 mg twice-daily, 200 mg twice-daily, and 600 mg once-daily cohorts, respectively, 50.0%, 64.4%, and 68.8% completed week 24. A ≥50% reduction in total symptom score was achieved by 35.7% and 28.6% of patients in the 200 mg twice-daily cohort and 32.3% and 35.5% in the 600 mg once-daily cohort at week 12 (primary end point) and 24, respectively. By contrast, two patients (20%) in the 100 mg twice-daily cohort had ≥50% total symptom score reduction at weeks 12 and 24. For the 200 mg twice-daily and 600 mg once-daily cohorts, the median spleen volume reductions at week 12 were 14.2% and 17.4%, respectively. Furthermore, 21/39 (53.8%) patients who required red blood cell transfusions during the 12 weeks preceding treatment initiation achieved a ≥50% reduction in the number of red blood cell units transfused during study weeks 1–24. Only one patient discontinued for grade 3 thrombocytopenia. Non-hematologic adverse events were largely grade 1 or 2; the most common was fatigue. Treatment with INCB039110 resulted in clinically meaningful symptom relief, modest spleen volume reduction, and limited myelosuppression. PMID:27789678

  3. A phase II open label trial evaluating safety and efficacy of a telomerase peptide vaccination in patients with advanced hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Ayuso Carmen

    2010-05-01

    Full Text Available Abstract Background The sole effective option for patients with advanced HCC is sorafenib and there is an urgent need to develop new therapeutic approaches. Immunotherapy is a promising option that deserves major investigation. In this open label, single arm clinical trial, we analyzed the effect of a low dose cyclophosphamide treatment in combination with a telomerase peptide (GV1001 vaccination in patients with advanced HCC. Methods 40 patients with advanced HCC were treated with 300 mg/m2 cyclophosphamide on day -3 followed by GM-CSF + GV1001 vaccinations on days 1, 3, 5, 8, 15, 22, 36 followed by 4-weekly injections. Primary endpoint of this phase II trial was tumor response; secondary endpoints evaluated were TTP, TTSP, PFS, OS, safety and immune responses. Results None of the patients had a complete or partial response to treatment, 17 patients (45.9% demonstrated a stable disease six months after initiation of treatment. The median TTP was 57.0 days; the median TTSP was estimated to be 358.0 days. Cyclophosphamide, GV1001 and GM-CSF treatment were well tolerated and most adverse events, which were of grade 1 or 2, were generally related to the injection procedure and injection site reactions. GV1001 treatment resulted in a decrease in CD4+CD25+Foxp3+ regulatory T cells; however, no GV1001 specific immune responses were detected after vaccination. Conclusions Low dose cyclophosphamide treatment followed by GV1001 vaccinations did not show antitumor efficacy as per tumor response and time to progression. Further studies are needed to analyze the effect of a combined chemo-immunotherapy to treat patients with HCC. Trial registration NCT00444782

  4. Itolizumab in combination with methotrexate modulates active rheumatoid arthritis: safety and efficacy from a phase 2, randomized, open-label, parallel-group, dose-ranging study.

    Science.gov (United States)

    Chopra, Arvind; Chandrashekara, S; Iyer, Rajgopalan; Rajasekhar, Liza; Shetty, Naresh; Veeravalli, Sarathchandra Mouli; Ghosh, Alakendu; Merchant, Mrugank; Oak, Jyotsna; Londhey, Vikram; Barve, Abhijit; Ramakrishnan, M S; Montero, Enrique

    2016-04-01

    The objective of this study was to assess the safety and efficacy of itolizumab with methotrexate in active rheumatoid arthritis (RA) patients who had inadequate response to methotrexate. In this open-label, phase 2 study, 70 patients fulfilling American College of Rheumatology (ACR) criteria and negative for latent tuberculosis were randomized to four arms: 0.2, 0.4, or 0.8 mg/kg itolizumab weekly combined with oral methotrexate, and methotrexate alone (2:2:2:1). Patients were treated for 12 weeks, followed by 12 weeks of methotrexate alone during follow-up. Twelve weeks of itolizumab therapy was well tolerated. Forty-four patients reported adverse events (AEs); except for six severe AEs, all others were mild or moderate. Infusion-related reactions mainly occurred after the first infusion, and none were reported after the 11th infusion. No serum anti-itolizumab antibodies were detected. In the full analysis set, all itolizumab doses showed evidence of efficacy. At 12 weeks, 50 % of the patients achieved ACR20, and 58.3 % moderate or good 28-joint count Disease Activity Score (DAS-28) response; at week 24, these responses were seen in 22 and 31 patients. Significant improvements were seen in Short Form-36 Health Survey and Health Assessment Questionnaire Disability Index scores. Overall, itolizumab in combination with methotrexate was well tolerated and efficacious in RA for 12 weeks, with efficacy persisting for the entire 24-week evaluation period. (Clinical Trial Registry of India, http://ctri.nic.in/Clinicaltrials/login.php , CTRI/2008/091/000295).

  5. Safety and tolerability of intrathecal delivery of autologous bone marrow nucleated cells in children with cerebral palsy: an open-label phase I trial.

    Science.gov (United States)

    Mancías-Guerra, Consuelo; Marroquín-Escamilla, Alma Rosa; González-Llano, Oscar; Villarreal-Martínez, Laura; Jaime-Pérez, José Carlos; García-Rodríguez, Fernando; Valdés-Burnes, Sagrario Lisete; Rodríguez-Romo, Laura Nely; Barrera-Morales, Dinorah Catalina; Sánchez-Hernández, José Javier; Cantú-Rodríguez, Olga Graciela; Gutiérrez-Aguirre, César Homero; Gómez-De León, Andrés; Elizondo-Riojas, Guillermo; Salazar-Riojas, Rosario; Gómez-Almaguer, David

    2014-06-01

    Cerebral palsy (CP) is related to severe perinatal hypoxia with permanent brain damage in nearly 50% of surviving preterm infants. Cell therapy is a potential therapeutic option for CP by several mechanisms, including immunomodulation through cytokine and growth factor secretion. In this phase I open-label clinical trial, 18 pediatric patients with CP were included to assess the safety of autologous bone marrow-derived total nucleated cell (TNC) intrathecal and intravenous injection after stimulation with granulocyte colony-stimulating factor. Motor, cognitive, communication, personal-social and adaptive areas were evaluated at baseline and 1 and 6 months after the procedure through the use of the Battelle Developmental Inventory. Magnetic resonance imaging was performed at baseline and 6 months after therapy. This study was registered in ClinicaTrials.gov (NCT01019733). A median of 13.12 × 10(8) TNCs (range, 4.83-53.87) including 10.02 × 10(6) CD34+ cells (range, 1.02-29.9) in a volume of 7 mL (range, 4-10.5) was infused intrathecally. The remaining cells from the bone marrow aspirate were administered intravenously; 6.01 × 10(8) TNCs (range, 1.36-17.85), with 3.39 × 10(6) cells being CD34+. Early adverse effects included headache, vomiting, fever and stiff neck occurred in three patients. No serious complications were documented. An overall 4.7-month increase in developmental age according to the Battelle Developmental Inventory, including all areas of evaluation, was observed (±SD 2.63). No MRI changes at 6 months of follow-up were found. Subarachnoid placement of autologous bone marrow-derived TNC in children with CP is a safe procedure. The results suggest a possible increase in neurological function. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  6. Antiproliferative effects of lanreotide autogel in patients with progressive, well-differentiated neuroendocrine tumours: a Spanish, multicentre, open-label, single arm phase II study.

    Science.gov (United States)

    Martín-Richard, Marta; Massutí, Bartomeu; Pineda, Eva; Alonso, Vicente; Marmol, Maribel; Castellano, Daniel; Fonseca, Emilio; Galán, Antonio; Llanos, Marta; Sala, Maria Angeles; Pericay, Carlos; Rivera, Fernando; Sastre, Javier; Segura, Angel; Quindós, Maria; Maisonobe, Pascal

    2013-09-20

    Somatostatin analogues (SSAs) are indicated to relieve carcinoid syndrome but seem to have antiproliferative effects on neuroendocrine tumours (NETs). This is the first prospective study investigating tumour stabilisation with the long-acting SSA lanreotide Autogel in patients with progressive NETs. This was a multicentre, open-label, phase II trial conducted in 17 Spanish specialist centres. Patients with well-differentiated NETs and radiologically confirmed progression within the previous 6 months received lanreotide Autogel, 120 mg every 28 days over ≤92 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, tumour biomarkers, symptom control, quality of life (QoL), and safety. Radiographic imaging was assessed by a blinded central radiologist. Of 30 patients included in the efficacy and safety analyses, 40% had midgut tumours and 27% pancreatic tumours; 63% of tumours were functioning. Median PFS time was 12.9 (95% CI: 7.9, 16.5) months, and most patients achieved disease stabilisation (89%) or partial response (4%). No deterioration in QoL was observed. Nineteen patients (63%) experienced treatment-related adverse events, most frequently diarrhoea and asthenia; only one treatment-related adverse event (aerophagia) was severe. Lanreotide Autogel provided effective tumour stabilisation and PFS >12 months in patients with progressive NETs ineligible for surgery or chemotherapy, with a safety profile consistent with the pharmacology of the class. ClinicalTrials.gov Identifier NCT00326469; EU Clinical Trial Register EudraCT no 2004-002871-18.

  7. Bumetanide for the treatment of seizures in newborn babies with hypoxic ischaemic encephalopathy (NEMO) : an open-label, dose finding, and feasibility phase 1/2 trial

    NARCIS (Netherlands)

    Pressler, Ronit M.; Boylan, Geraldine B.; Marlow, Neil; Blennow, Mats; Chiron, Catherine; Cross, J. Helen; de Vries, Linda S.; Hallberg, Boubou; Hellstrom-Westas, Lena; Jullien, Vincent; Livingstone, Vicki; Mangum, Barry; Murphy, Brendan; Murray, Deirdre; Pons, Gerard; Rennie, Janet; Swarte, Renate; Toet, Mona C.; Vanhatalo, Sampsa; Zohar, Sarah

    Background Predinical data suggest that the loop-diuretic bumetanide might be an effective treatment for neonatal seizures. We aimed to assess dose and feasibility of intravenous bumetanide as an add-on to phenobarbital for treatment of neonatal seizures. Methods In this open-label, dose finding,

  8. No evidence of harms of probiotic Lactobacillus rhamnosus GG ATCC 53103 in healthy elderly-a Phase I Open Label Study to assess safety, tolerability and cytokine responses

    Science.gov (United States)

    Although Lactobacillus rhamnosus GG ATCC 53103 (LGG) has been consumed since the mid 1990s by between 2 and 5 million people daily, the scientific literature lacks rigorous clinical trials that describe the potential harms of LGG, particularly in the elderly. The primary objective of this open label...

  9. Bumetanide for the treatment of seizures in newborn babies with hypoxic ischaemic encephalopathy (NEMO) : an open-label, dose finding, and feasibility phase 1/2 trial

    NARCIS (Netherlands)

    Pressler, Ronit M.; Boylan, Geraldine B.; Marlow, Neil; Blennow, Mats; Chiron, Catherine; Cross, J. Helen; de Vries, Linda S.; Hallberg, Boubou; Hellstrom-Westas, Lena; Jullien, Vincent; Livingstone, Vicki; Mangum, Barry; Murphy, Brendan; Murray, Deirdre; Pons, Gerard; Rennie, Janet; Swarte, Renate; Toet, Mona C.; Vanhatalo, Sampsa; Zohar, Sarah

    2015-01-01

    Background Predinical data suggest that the loop-diuretic bumetanide might be an effective treatment for neonatal seizures. We aimed to assess dose and feasibility of intravenous bumetanide as an add-on to phenobarbital for treatment of neonatal seizures. Methods In this open-label, dose finding, an

  10. A multicenter, primary care-based, open-label study to identify behaviors related to prescription opioid misuse, abuse, and diversion in opioid-experienced patients with chronic moderate-to-severe pain

    Directory of Open Access Journals (Sweden)

    Setnik B

    2015-07-01

    Full Text Available Beatrice Setnik,1 Carl L Roland,1 Kenneth W Sommerville,1,2 Glenn C Pixton,1 Robert Berke,3,4 Anne Calkins,5 Veeraindar Goli1,2 1Pfizer Inc, 2Duke University Medical Center, Durham, NC, 3Family Health Medical Services PLLC, Mayville, NY, 4Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, NY, 5New York Spine & Wellness Center, Syracuse, NY, USA Objective: To compare the investigator assessment of patient risk for prescription opioid misuse, abuse, and diversion with patient self-reports of these activities in a population with chronic pain. Methods: As a secondary objective of an open-label, multicenter, primary care-based clinical study to evaluate the success of converting opioid-experienced patients with chronic pain to morphine sulfate with sequestered naltrexone hydrochloride, risk for misuse, abuse, and diversion was assessed using two nonvalidated questionnaires: one was completed by the investigator and another by the patient (Self-Reported Misuse, Abuse, and Diversion [SR-MAD]. In addition, the validated Current Opioid Misuse Measure (COMM test and urine drug test were used. Results: Of the 684 patients assessed by the investigators, 537 returned the self-assessment, SR-MAD. Most patients were assigned by the investigator as low risk for misuse (84.2%, abuse (89.3%, and diversion (94.3%. Of the patients who returned SR-MAD, 60% indicated having taken more opioids than prescribed and 10.9% reported chewing or crushing their opioids in the past. Of the patients who completed COMM, 40.6% were deemed as having aberrant behaviors. COMM results correlated with the risk levels from the investigator assessment. One-third of patients (33.8% had at least one abnormal urine drug test result. Conclusion: More research is needed to better understand the gap between the investigator assessment of potential risk for misuse, abuse, and diversion and the actual extent of these behaviors among patients with

  11. Prophylactic onabotulinumtoxinA in patients with chronic migraine and comorbid depression: An open-label, multicenter, pilot study of efficacy, safety and effect on headache-related disability, depression, and anxiety

    Science.gov (United States)

    Boudreau, Guy P; Grosberg, Brian M; McAllister, Peter J; Lipton, Richard B; Buse, Dawn C

    2015-01-01

    Background Chronic migraine is associated with significant headache-related disability and psychiatric comorbidity. OnabotulinumtoxinA (BOTOX®) is effective and well tolerated in the prophylactic treatment of chronic migraine. This study aimed to provide preliminary data on the efficacy and safety of prophylactic onabotulinumtoxinA in patients with chronic migraine and comorbid depressive symptoms. Methods This was a prospective, open-label, multicenter pilot study. Eligible patients met International Classification of Headache Disorders 2nd edition Revision criteria for chronic migraine and had associated depressive symptoms, including Patient Health Questionnaire depression module scores of 5–19. Eligible participants received 155 units of onabotulinumtoxinA, according to the PREEMPT protocol, at baseline and week 12. Assessments included headache frequency, the Headache Impact Test™, the Migraine Disability Assessment, the Beck Depression Inventory®-II, the nine-item Patient Health Questionnaire depression module, and the seven-item Generalized Anxiety Disorder questionnaire. Adverse events were also monitored. Results Overall, 32 participants received treatment. At week 24, there were statistically significant mean (standard deviation [SD]) improvements relative to baseline in the number of headache/migraine-free days (+8.2 [5.8]) (P<0.0001) and in the number of headache/migraine days (−8.2 [5.8]) (P<0.0001) per 30-day period. In addition, there were significant improvements in Headache Impact Test scores (−6.3 [6.9]) (P=0.0001) and Migraine Disability Assessment scores (−44.2 [67.5]) (P=0.0058). From baseline to week 24, statistically significant improvements were also seen in Beck Depression Inventory-II (−7.9 [6.0]) (P<0.0001), Patient Health Questionnaire depression module (−4.3 [4.7]) (P<0.0001), and Generalized Anxiety Disorder questionnaire (−3.5 [5.0]) (P=0.0002) scores. No serious adverse events were reported. Adverse events

  12. Safety and tolerability of pasireotide long-acting release in acromegaly-results from the acromegaly, open-label, multicenter, safety monitoring program for treating patients who have a need to receive medical therapy (ACCESS) study.

    Science.gov (United States)

    Fleseriu, Maria; Rusch, Elisha; Geer, Eliza B

    2017-01-01

    Pasireotide long-acting release is a somatostatin analog that is indicated for treatment of patients with acromegaly. This analysis documents the safety of pasireotide long-acting release in patients with acromegaly enrolled in the ACCESS trial (ClinicalTrials.gov identifier: NCT01995734). ACCESS is an open-label, multicenter, single-arm, expanded-treatment protocol designed to provide patients access to pasireotide long-acting release pending regulatory approval. Patients received pasireotide long-acting release 40 mg administered intramuscularly every 28 days. The primary outcome was the proportion of patients having a treatment-emergent grade ≥3 or serious adverse event. Efficacy data were not collected. Forty-four adult patients with active acromegaly were enrolled in the study for an average of 37.6 weeks (range, 4-70 weeks). Twenty-five grade ≥3 treatment-emergent adverse events were reported in 11 patients (25.0 %), 3 of whom (27.3 %) experienced grade ≥3 hyperglycemia. In patients treated with pasireotide long-acting release for ≥3 months (n = 42), mean glycated hemoglobin and fasting plasma glucose levels increased significantly from 5.9 % and 100.4 mg/dL at baseline to 6.8 % and 135.9 mg/dL at 3 months, respectively. Ten patients (22.7 %) were treated with pasireotide long-acting release for ≥15 months, after which mean glycated hemoglobin and fasting plasma glucose levels were 6.3 % and 123 mg/dL, respectively. Twenty-one patients (48 %) initiated antidiabetic medication. Grade ≥3 adverse events (primary outcome) were reported in 25.0 % of acromegaly patients treated with pasireotide long-acting release in a clinical setting. Hyperglycemia-related adverse events were reported in 45.5 % of patients, but were typically manageable, supporting the role of pasireotide long-acting release as a safe treatment option for acromegaly patients.

  13. Achieving lipid goals with rosuvastatin compared with simvastatin in high risk patients in real clinical practice: a randomized, open-label, parallel-group, multi-center study: the DISCOVERY-Beta study

    Directory of Open Access Journals (Sweden)

    Toivo Laks

    2008-12-01

    Full Text Available Toivo Laks1, Ester Keba2, Mariann Leiner3, Eero Merilind4, Mall Petersen5, Sirje Reinmets6, Sille Väli7, Terje Sööt8, Karin Otter81Clinic of Internal Medicine, North-Estonia Regional Hospital, Tallinn, Estonia; 2Clinic of Internal Medicine, Viljandi County Hospital, Viljandi, Estonia; 3Mustamäe Family Doctors Centre, Tallinn, Estonia; 4Nõmme Family Doctors Centre, Tallinn, Estonia; 5Saku Health Centre, Saku, Estonia; 6Kristiine Family Doctors, Tallinn, Estonia; 7Family Doctor Sille Väli, Kuressaare, Estonia; 8AstraZeneca, Tallinn, EstoniaAbstract: The aim of this multi-center, open-label, randomized, parallel-group trial was to compare the efficacy of rosuvastatin with that of simvastatin in achieving the 1998 European Atherosclerosis Society (EAS lipid treatment goals. 504 patients (≥18 years with primary hypercholesterolemia and a 10-year cardiovascular (CV risk >20% or history of coronary heart disease (CHD or other established atherosclerotic disease were randomized in a 2:1 ratio to receive rosuvastatin 10 mg or simvastatin 20 mg once daily for 12 weeks. A significantly higher proportion of patients achieved 1998 EAS low-density lipoprotein cholesterol (LDL-C goal after 12 weeks of treatment with rosuvastatin 10 mg compared to simvastatin 20 mg (64 vs 51.5%, p < 0.01. Similarly, significantly more patients achieved the 1998 EAS total cholesterol (TC goal and the 2003 EAS LDL-C and TC goals (p < 0.001 with rosuvastatin 10 mg compared with simvastatin 20 mg. The incidence of adverse events and the proportion of patients who discontinued study treatment were similar between treatment groups. In conclusion, in the DISCOVERY-Beta Study in patients with primary hypercholesterolemia greater proportion of patients in the rosuvastatin 10 mg group achieved the EAS LDL-C treatment goal compared with the simvastatin 20 mg group. Drug tolerability was similar across both treatment groups.Keywords: hypercholesterolemia, low-density lipoprotein

  14. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study

    Science.gov (United States)

    Fenaux, Pierre; Mufti, Ghulam J; Hellstrom-Lindberg, Eva; Santini, Valeria; Finelli, Carlo; Giagounidis, Aristoteles; Schoch, Robert; Gattermann, Norbert; Sanz, Guillermo; List, Alan; Gore, Steven D; Seymour, John F; Bennett, John M; Byrd, John; Backstrom, Jay; Zimmerman, Linda; McKenzie, David; Beach, C L; Silverman, Lewis R

    2014-01-01

    Summary Background Drug treatments for patients with high-risk myelodysplastic syndromes provide no survival advantage. In this trial, we aimed to assess the effect of azacitidine on overall survival compared with the three commonest conventional care regimens. Methods In a phase III, international, multicentre, controlled, parallel-group, open-label trial, patients with higher-risk myelodysplastic syndromes were randomly assigned one-to-one to receive azacitidine (75 mg/m² per day for 7 days every 28 days) or conventional care (best supportive care, low-dose cytarabine, or intensive chemotherapy as selected by investigators before randomisation). Patients were stratified by French–American–British and international prognostic scoring system classifications; randomisation was done with a block size of four. The primary endpoint was overall survival. Efficacy analyses were by intention to treat for all patients assigned to receive treatment. This study is registered with ClinicalTrials.gov, number NCT00071799. Findings Between Feb 13, 2004, and Aug 7, 2006, 358 patients were randomly assigned to receive azacitidine (n=179) or conventional care regimens (n=179). Four patients in the azacitidine and 14 in the conventional care groups received no study drugs but were included in the intention-to-treat efficacy analysis. After a median follow-up of 21·1 months (IQR 15·1–26·9), median overall survival was 24·5 months (9·9–not reached) for the azacitidine group versus 15·0 months (5·6–24·1) for the conventional care group (hazard ratio 0·58; 95% CI 0·43–0·77; stratified log-rank p=0·0001). At last follow-up, 82 patients in the azacitidine group had died compared with 113 in the conventional care group. At 2 years, on the basis of Kaplan-Meier estimates, 50·8% (95% CI 42·1–58·8) of patients in the azacitidine group were alive compared with 26·2% (18·7–34·3) in the conventional care group (p<0·0001). Peripheral cytopenias were the most

  15. Randomized open-label phase II study comparing oxycodone-naloxone with oxycodone in early return of gastrointestinal function after laparoscopic colorectal surgery.

    Science.gov (United States)

    Creamer, F; Balfour, A; Nimmo, S; Foo, I; Norrie, J D; Williams, L J; Fearon, K C; Paterson, H M

    2017-01-01

    Combined oral modified-release oxycodone-naloxone may reduce opioid-induced postoperative gut dysfunction. This study examined the feasibility of a randomized trial of oxycodone-naloxone within the context of enhanced recovery for laparoscopic colorectal resection. In a single-centre open-label phase II feasibility study, patients received analgesia based on either oxycodone-naloxone or oxycodone. Primary endpoints were recruitment, retention and protocol compliance. Secondary endpoints included a composite endpoint of gut function (tolerance of solid food, low nausea/vomiting score, passage of flatus or faeces). Eighty-two patients were screened and 62 randomized (76 per cent); the attrition rate was 19 per cent (12 of 62), leaving 50 patients who received the allocated intervention with 100 per cent follow-up and retention (modified intention-to-treat cohort). Protocol compliance was more than 90 per cent. Return of gut function by day 3 was similar in the two groups: 13 (48 per cent) of 27 in the oxycodone-naloxone group and 15 (65 per cent) of 23 in the control group (95 per cent c.i. for difference -10·0 to 40·7 per cent; P = 0·264). However, patients in the oxycodone-naloxone group had a shorter time to first bowel movement (mean(s.d.) 87(38) h versus 111(37) h in the control group; 95 per cent c.i. for difference 2·3 to 45·4 h, P = 0·031) and reduced total (oral plus parenteral) opioid consumption (mean(s.d.) 78(36) versus 94(56) mg respectively; 95 per cent c.i. for difference -10·2 to 42·8 mg, P = 0·222). High participation, retention and protocol compliance confirmed feasibility. Potential benefits of oxycodone-naloxone in reducing time to bowel movement and total opioid consumption could be tested in a randomized trial. Registration number: NCT02109640 (https://www.clinicaltrials.gov/). © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

  16. EXpanding Treatment for Existing Neurological Disease (EXTEND): An Open-Label Phase II Clinical Trial of Hydroxyurea Treatment in Sickle Cell Anemia

    Science.gov (United States)

    Little, Courtney R; Reid, Marvin E; Soares, Deanne P; Taylor-Bryan, Carolyn; Knight-Madden, Jennifer M; Stuber, Susan E; Badaloo, Asha V; Aldred, Karen; Wisdom-Phipps, Margaret E; Latham, Teresa; Ware, Russell E

    2016-01-01

    Background Cerebral vasculopathy in sickle cell anemia (SCA) begins in childhood and features intracranial arterial stenosis with high risk of ischemic stroke. Stroke risk can be reduced by transcranial doppler (TCD) screening and chronic transfusion therapy; however, this approach is impractical in many developing countries. Accumulating evidence supports the use of hydroxyurea for the prevention and treatment of cerebrovascular disease in children with SCA. Recently we reported that hydroxyurea significantly reduced the conversion from conditional TCD velocities to abnormal velocities; whether hydroxyurea can be used for children with newly diagnosed severe cerebrovascular disease in place of starting transfusion therapy remains unknown. Objective The primary objective of the EXpanding Treatment for Existing Neurological Disease (EXTEND) trial is to investigate the effect of open label hydroxyurea on the maximum time-averaged mean velocity (TAMV) after 18 months of treatment compared to the pre-treatment value. Secondary objectives include the effects of hydroxyurea on serial TCD velocities, the incidence of neurological and non-neurological events, quality of life (QOL), body composition and metabolism, toxicity and treatment response, changes to brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), genetic and serologic markers of disease severity, and cognitive and pulmonary function. Methods This prospective Phase II trial will enroll children with SCA in Jamaica, between the ages of 2 and 17 years, with either conditional (170-199 cm/sec) or abnormal (≥ 200 cm/sec) TCD velocities. Oral hydroxyurea will be administered daily and escalated to the maximum tolerated dose (MTD). Participants will be seen in the Sickle Cell Unit (SCU) in Kingston, Jamaica monthly until achieving MTD, and then every 3 months. TCD will be performed every 6 months. Results Currently, 43 participants have been enrolled out of a projected 50. There was one

  17. Transcriptomic Profile of Whole Blood Cells from Elderly Subjects Fed Probiotic Bacteria Lactobacillus rhamnosus GG ATCC 53103 (LGG in a Phase I Open Label Study.

    Directory of Open Access Journals (Sweden)

    Gloria Solano-Aguilar

    Full Text Available We examined gene expression of whole blood cells (WBC from 11 healthy elderly volunteers participating on a Phase I open label study before and after oral treatment with Lactobacillus rhamnosus GG-ATCC 53103 (LGG using RNA-sequencing (RNA-Seq. Elderly patients (65-80 yrs completed a clinical assessment for health status and had blood drawn for cellular RNA extraction at study admission (Baseline, after 28 days of daily LGG treatment (Day 28 and at the end of the study (Day 56 after LGG treatment had been suspended for 28 days. Treatment compliance was verified by measuring LGG-DNA copy levels detected in host fecal samples. Normalized gene expression levels in WBC RNA were analyzed using a paired design built within three analysis platforms (edgeR, DESeq2 and TSPM commonly used for gene count data analysis. From the 25,990 transcripts detected, 95 differentially expressed genes (DEGs were detected in common by all analysis platforms with a nominal significant difference in gene expression at Day 28 following LGG treatment (FDR<0.1; 77 decreased and 18 increased. With a more stringent significance threshold (FDR<0.05, only two genes (FCER2 and LY86, were down-regulated more than 1.5 fold and met the criteria for differential expression across two analysis platforms. The remaining 93 genes were only detected at this threshold level with DESeq2 platform. Data analysis for biological interpretation of DEGs with an absolute fold change of 1.5 revealed down-regulation of overlapping genes involved with Cellular movement, Cell to cell signaling interactions, Immune cell trafficking and Inflammatory response. These data provide evidence for LGG-induced transcriptional modulation in healthy elderly volunteers because pre-treatment transcription levels were restored at 28 days after LGG treatment was stopped. To gain insight into the signaling pathways affected in response to LGG treatment, DEG were mapped using biological pathways and genomic data mining

  18. Immunogenicity and safety of a quadrivalent influenza vaccine in children and adolescents in Taiwan: A phase III open-label trial

    Directory of Open Access Journals (Sweden)

    Chun-Yi Lu

    2016-01-01

    Full Text Available Until recently, all seasonal influenza vaccines have been trivalent, containing strains A(H1N1, A(H3N2, and one of the two B strain lineages (Yamagata or Victoria, resulting in frequent mismatches between the circulating B strain lineage and that included in the vaccine. A quadrivalent, inactivated, split-virion influenza vaccine (IIV4 containing strains from both B lineages has been developed to address this. We performed an open-label phase III study to assess the immunogenicity and safety of the 2013–2014 Northern Hemisphere formulation of IIV4 in children and adolescents 9–17 years of age in Taiwan. Participants were vaccinated with one dose of IIV4 by intramuscular or deep subcutaneous injection. Hemagglutinin inhibition (HAI titers were measured before and 21 days after vaccination. Solicited injection-site and systemic reactions were assessed for up to 7 days after vaccination, and adverse events (AEs were recorded until day 21. One hundred participants were included. Despite relatively high pre-vaccination titers, post-vaccination HAI titers increased for all four strains, with geometric mean ratios (day 21/day 0 of 2.29 for A(H1N1, 2.05 for A(H3N2, 3.33 for B/Massachusetts (Yamagata lineage, and 4.59 for B/Brisbane (Victoria lineage. Post-vaccination seroprotection rates were 99% for A(H3N2 and 100% for A(H1N1, B/Massachusetts, and B/Brisbane. Due to high pre-vaccination titers, rates of seroconversion/significant increase of HAI titer were relatively low at 24% for A(H1N1, 20% for A(H3N2, 39% for B/Massachusetts, and 48% for B/Brisbane. Injection-site pain (56%, myalgia (45%, and malaise (15% were the most frequently reported solicited reactions, and most solicited reactions were mild or moderate. No treatment-related AEs, immediate unsolicited AEs, unsolicited non-serious injection-site AEs, grade 3 unsolicited AEs, or serious AEs were reported. In conclusion, this study showed that the 2013–2014 Northern Hemisphere

  19. Prophylactic onabotulinumtoxinA in patients with chronic migraine and comorbid depression: An open-label, multicenter, pilot study of efficacy, safety and effect on headache-related disability, depression, and anxiety

    Directory of Open Access Journals (Sweden)

    Boudreau GP

    2015-02-01

    Full Text Available Guy P Boudreau,1 Brian M Grosberg,2 Peter J McAllister,3 Richard B Lipton,2 Dawn C Buse2 1Clinique de la Migraine et Céphalées, Département de Neurologie, Centre Hospitalier de L’Université de Montréal, Hôpital Notre-Dame, Montreal, QC, Canada; 2Montefiore Headache Center and the Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA; 3New England Institute for Neurology and Headache, Stamford, and The Frank H Netter School of Medicine at Quinnipiac University, Hamden, CT, USA Background: Chronic migraine is associated with significant headache-related disability and psychiatric comorbidity. OnabotulinumtoxinA (BOTOX® is effective and well tolerated in the prophylactic treatment of chronic migraine. This study aimed to provide preliminary data on the efficacy and safety of prophylactic onabotulinumtoxinA in patients with chronic migraine and comorbid depressive symptoms. Methods: This was a prospective, open-label, multicenter pilot study. Eligible patients met International Classification of Headache Disorders 2nd edition Revision criteria for chronic migraine and had associated depressive symptoms, including Patient Health Questionnaire depression module scores of 5–19. Eligible participants received 155 units of onabotulinumtoxinA, according to the PREEMPT protocol, at baseline and week 12. Assessments included headache frequency, the Headache Impact Test™, the Migraine Disability Assessment, the Beck Depression Inventory®-II, the nine-item Patient Health Questionnaire depression module, and the seven-item Generalized Anxiety Disorder questionnaire. Adverse events were also monitored. Results: Overall, 32 participants received treatment. At week 24, there were statistically significant mean (standard deviation [SD] improvements relative to baseline in the number of headache/migraine-free days (+8.2 [5.8] (P<0.0001 and in the number of headache/migraine days (–8.2 [5.8] (P<0.0001 per 30-day period. In

  20. Open-label phase II clinical trial in 75 patients with advanced hepatocellular carcinoma receiving daily dose of tableted liver cancer vaccine, hepcortespenlisimut-L

    Directory of Open Access Journals (Sweden)

    Tarakanovskaya MG

    2017-04-01

    Full Text Available Marina G Tarakanovskaya,1 Jigjidsuren Chinburen,2 Purev Batchuluun,2 Chogsom Munkhzaya,2 Genden Purevsuren,2 Dorjiin Dandii,3 Tsogkhuu Hulan,3 Dandii Oyungerel,4 Galyna A Kutsyna,5 Alan A Reid,6 Vika Borisova,6 Allen I Bain,7 Vichai Jirathitikal,7 Aldar S Bourinbaiar6–8 1Ekomed LLC, 2National Cancer Center, 3Monserum LLC, 4National Center for Public Health, Ulaanbaatar, Mongolia; 5Department of Infectious Diseases, Luhansk State Medical University, Luhansk, Ukraine; 6Immunitor China Ltd, Beijing, People’s Republic of China; 7Immunitor Inc, Vancouver, BC, Canada; 8Immunitor LLC, Ulaanbaatar, Mongolia Background: An increasing number of studies is now devoted to immunotherapy of cancer. We evaluated the clinical benefit of hepcortespenlisimut-L (Hepko-V5 [formerly known as V5]—an oral therapeutic vaccine designated by the United States Food and Drug Administration (FDA as an orphan drug for treatment of hepatocellular carcinoma (HCC. V5 was initially developed by us in 2002 to treat hepatitis B or C viral infections and liver cirrhosis.Methods: The outcome of open-label Phase II trial of daily dose of V5 pill was analyzed retrospectively. Over a period of 5 years, 75 patients with advanced HCC were enrolled, consisting of 29 (38.7% females and 46 (61.3% males with a median age of 60 years (mean 61.6±8.1 years. Out of these, 23 (30.7% had hepatitis B and 34 (45.3% had hepatitis C infections, including 9 (12% with dual infection, 4 (5.3% negative for both viruses, and 5 (6.7% without established viral diagnosis. Most patients (94.7% had underlying liver cirrhosis of varying severity.Results: After a median of 2 months of treatment, 50 out of 75 patients had experienced a decline in serum levels of the tumor marker, alpha-fetoprotein (AFP (66.7%; P=0.006 by Wilcoxon signed rank test. Baseline median AFP levels were 245.2 IU/mL (mean 4,233; range 7.2–92,407; 95% confidence interval [CI] 1,186–7,280 and post-treatment values were 102.3 IU

  1. Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial.

    Science.gov (United States)

    Hillmen, Peter; Robak, Tadeusz; Janssens, Ann; Babu, K Govind; Kloczko, Janusz; Grosicki, Sebastian; Doubek, Michael; Panagiotidis, Panagiotis; Kimby, Eva; Schuh, Anna; Pettitt, Andrew R; Boyd, Thomas; Montillo, Marco; Gupta, Ira V; Wright, Oliver; Dixon, Iestyn; Carey, Jodi L; Chang, Chai-Ni; Lisby, Steen; McKeown, Astrid; Offner, Fritz

    2015-05-09

    Treatment for patients with chronic lymphocytic leukaemia who are elderly or who have comorbidities is challenging because fludarabine-based chemoimmunotherapies are mostly not suitable. Chlorambucil remains the standard of care in many countries. We aimed to investigate whether the addition of ofatumumab to chlorambucil could lead to better clinical outcomes than does treatment with chlorambucil alone, while also being tolerable for patients who have few treatment options. We carried out a randomised, open-label, phase 3 trial for treatment-naive patients with chronic lymphocytic leukaemia in 109 centres in 16 countries. We included patients who had active disease needing treatment, but in whom fludarabine-based treatment was not possible. We randomly assigned patients (1:1) to receive oral chlorambucil (10 mg/m(2)) on days 1-7 of a 28 day treatment course or to receive chlorambucil by this schedule plus intravenous ofatumumab (cycle 1: 300 mg on day 1 and 1000 mg on day 8; subsequent cycles: 1000 mg on day 1) for three to 12 cycles. Assignment was done with a randomisation list that was computer generated at GlaxoSmithKline, and was stratified, in a block size of two, by age, disease stage, and performance status. The primary endpoint was progression-free survival in the intention-to-treat population and assessment was done by an independent review committee that was masked to group assignment. The study is registered with ClinicalTrials.gov, number NCT00748189. We enrolled 447 patients, median age 69 years (range 35-92). Between Dec 22, 2008, and May 26, 2011, we randomly assigned 221 patients to chlorambucil plus ofatumumab and 226 patients to chlorambucil alone. Median progression-free survival was 22·4 months (95% CI 19·0-25·2) in the group assigned to chlorambucil plus ofatumumab compared with 13·1 months (10·6-13·8) in the group assigned to chlorambucil only (hazard ratio 0·57, 95% CI 0·45-0·72; pchlorambucil plus ofatumumab group (109 [50

  2. A phase 4, single-arm, open-label, pilot study of maraviroc, raltegravir and darunavir/r in HIV-1 adults with triple class failure: TERCETO study

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    P Patterson

    2012-11-01

    Full Text Available The purpose of this phase 4, single-arm, open-label study was to evaluate the safety, tolerability, efficacy, antiviral and immunological activity of maraviroc (MVC in combination with raltegravir (RGV and darunavir/r (DRV/r in adult HIV-1 infected patients (pts with limited treatment options. HIV-1 pts with documented virologic triple class failure or multi-drug class resistance defined as the presence of Q151 complex, 69 insertion complex and/or≥3 TAMs for NRTIs and K103N, G190S+Y181C or Y188L mutants for NNRTIs and≥3 RAMs (L10F/I/R/V; M46I/L; I54V/M/L; V82A/F/T/S; I84V; L90M for protease inhibitors (PIs were offered a triple drug regimen consisting of MVC 150 mg BID, RGV 400 mg BID and DRV/r 600/100 mg BID. Safety, lipid profile and virologic efficacy were evaluated at week 4, 12, 24, 36 and 48. Between January 2010 and March 2012, 27 pts were enrolled. Screening failure rate was 52% due to undetectable viral load (pVL or non R5 tropism type (Trofile™. Despite being heavily pre-treated pts, only 26% had negative tropism test at SCR. Baseline characteristics of 13 included pts were: 77% male, median age 43 years (IQR: 40.1–48.6, 38% had a prior AIDS-defining condition. Median BSL pVL was 23,350 cps/mL (4.4 log10 (IQR: 11,236–55,785 and median CD4 was 222 cells/mm3 (IQR: 179–318. Median time on NRTIs, NNRTIs and PIs were 10.7 (8.6–13.7, 1.7 (1.3–7.6 and 5.4 (4.7–10 years respectively. Pts had received a median of 2 PIs (IQR: 2–3. 8/13 pts showed thymidine analogue-associated mutations (TAMs, and≥2 were present in 5/13. Detectable NNRTI resistance-associated mutations (RAMs were present in 10/13 patients. 9/13 had≥4 primary PI RAMs. At 48 weeks, 2 pts had discontinued therapy (OIs related death (cryptococcal meningitis=1, withdrawn from the study on W36 due to blips despite not achieving criteria for virologic failure=1 and the remaining pts (11/13 achieved undetectable pVL and increased CD4 in 133 cell/mm3 from BSL (IQR

  3. Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial.

    Science.gov (United States)

    Prince, H Miles; Kim, Youn H; Horwitz, Steven M; Dummer, Reinhard; Scarisbrick, Julia; Quaglino, Pietro; Zinzani, Pier Luigi; Wolter, Pascal; Sanches, Jose A; Ortiz-Romero, Pablo L; Akilov, Oleg E; Geskin, Larisa; Trotman, Judith; Taylor, Kerry; Dalle, Stephane; Weichenthal, Michael; Walewski, Jan; Fisher, David; Dréno, Brigitte; Stadler, Rudolf; Feldman, Tatyana; Kuzel, Timothy M; Wang, Yinghui; Palanca-Wessels, Maria Corinna; Zagadailov, Erin; Trepicchio, William L; Zhang, Wenwen; Lin, Hui-Min; Liu, Yi; Huebner, Dirk; Little, Meredith; Whittaker, Sean; Duvic, Madeleine

    2017-08-05

    Cutaneous T-cell lymphomas are rare, generally incurable, and associated with reduced quality of life. Present systemic therapies rarely provide reliable and durable responses. We aimed to assess efficacy and safety of brentuximab vedotin versus conventional therapy for previously treated patients with CD30-positive cutaneous T-cell lymphomas. In this international, open-label, randomised, phase 3, multicentre trial, we enrolled adult patients with CD30-positive mycosis fungoides or primary cutaneous anaplastic large-cell lymphoma who had been previously treated. Patients were enrolled across 52 centres in 13 countries. Patients were randomly assigned (1:1) centrally by an interactive voice and web response system to receive intravenous brentuximab vedotin 1·8 mg/kg once every 3 weeks, for up to 16 3-week cycles, or physician's choice (oral methotrexate 5-50 mg once per week or oral bexarotene 300 mg/m(2) once per day) for up to 48 weeks. The primary endpoint was the proportion of patients in the intention-to-treat population achieving an objective global response lasting at least 4 months per independent review facility. Safety analyses were done in all patients who received at least one dose of study drug. This trial was registered with ClinicalTrials.gov, number NCT01578499. Between Aug 13, 2012, and July 31, 2015, 131 patients were enrolled and randomly assigned to a group (66 to brentuximab vedotin and 65 to physician's choice), with 128 analysed in the intention-to-treat population (64 in each group). At a median follow-up of 22·9 months (95% CI 18·4-26·1), the proportion of patients achieving an objective global response lasting at least 4 months was 56·3% (36 of 64 patients) with brentuximab vedotin versus 12·5% (eight of 64) with physician's choice, resulting in a between-group difference of 43·8% (95% CI 29·1-58·4; p<0·0001). Grade 3-4 adverse events were reported in 27 (41%) of 66 patients in the brentuximab vedotin group and 29 (47%) of 62

  4. Clonal Evolutionary Analysis during HER2 Blockade in HER2-Positive Inflammatory Breast Cancer: A Phase II Open-Label Clinical Trial of Afatinib +/- Vinorelbine

    Science.gov (United States)

    Schmid, Ramona; Arpornwirat, Wichit; Chitapanarux, Imjai; Ganju, Vinod; Im, Seock-Ah; Kim, Sung-Bae; Dechaphunkul, Arunee; Maneechavakajorn, Jedzada; Spector, Neil; Yau, Thomas; Afrit, Mehdi; Ahmed, Slim Ben; Johnston, Stephen R.; Gibson, Neil; Herrero, Javier; Swanton, Charles

    2016-01-01

    Background Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer associated with HER2 amplification, with high risk of metastasis and an estimated median survival of 2.9 y. We performed an open-label, single-arm phase II clinical trial (ClinicalTrials.gov NCT01325428) to investigate the efficacy and safety of afatinib, an irreversible ErbB family inhibitor, alone and in combination with vinorelbine in patients with HER2-positive IBC. This trial included prospectively planned exome analysis before and after afatinib monotherapy. Methods and Findings HER2-positive IBC patients received afatinib 40 mg daily until progression, and thereafter afatinib 40 mg daily and intravenous vinorelbine 25 mg/m2 weekly. The primary endpoint was clinical benefit; secondary endpoints were objective response (OR), duration of OR, and progression-free survival (PFS). Of 26 patients treated with afatinib monotherapy, clinical benefit was achieved in 9 patients (35%), 0 of 7 trastuzumab-treated patients and 9 of 19 trastuzumab-naïve patients. Following disease progression, 10 patients received afatinib plus vinorelbine, and clinical benefit was achieved in 2 of 4 trastuzumab-treated and 0 of 6 trastuzumab-naïve patients. All patients had treatment-related adverse events (AEs). Whole-exome sequencing of tumour biopsies taken before treatment and following disease progression on afatinib monotherapy was performed to assess the mutational landscape of IBC and evolutionary trajectories during therapy. Compared to a cohort of The Cancer Genome Atlas (TCGA) patients with HER2-positive non-IBC, HER2-positive IBC patients had significantly higher mutational and neoantigenic burden, more frequent gain-of-function TP53 mutations and a recurrent 11q13.5 amplification overlapping PAK1. Planned exploratory analysis revealed that trastuzumab-naïve patients with tumours harbouring somatic activation of PI3K/Akt signalling had significantly shorter PFS compared to those without

  5. Effect of Itraconazole and Rifampin on the Pharmacokinetics of Olaparib in Patients With Advanced Solid Tumors: Results of Two Phase I Open-label Studies.

    Science.gov (United States)

    Dirix, Luc; Swaisland, Helen; Verheul, Henk M W; Rottey, Sylvie; Leunen, Karin; Jerusalem, Guy; Rolfo, Christian; Nielsen, Dorte; Molife, L Rhoda; Kristeleit, Rebecca; Vos-Geelen, Judith de; Mau-Sørensen, Morten; Soetekouw, Patricia; van Herpen, Carla; Fielding, Anitra; So, Karen; Bannister, Wendy; Plummer, Ruth

    2016-10-01

    The metabolism of olaparib, a potent inhibitor of poly(ADP-ribose) polymerase (PARP) with demonstrated efficacy in patients with BRCA-mutated ovarian cancer, is mediated by cytochrome P450 (CYP) enzymes (predominantly CYP3A4/5). We assessed the potential of a CYP3A4 inhibitor (itraconazole) and inducer (rifampin) to alter the pharmacokinetic (PK) profile of olaparib following single oral tablet doses. Two Phase I, open-label, non-randomized trials were conducted in patients with advanced solid tumors. In Study 7, patients received olaparib alone and co-administered with itraconazole; in Study 8, a separate group of patients received olaparib alone and co-administered with rifampin. No interaction between itraconazole and olaparib was concluded if two-sided 90% CIs for the treatment ratios of AUC and/or AUC0-t and Cmax fell within the bioequivalence range of 0.80-1.25. An interaction between rifampin and olaparib was concluded if the lower limit of the 90% CI for the treatment ratios was 50% decrease in olaparib AUC or Cmax in the presence of rifampin compared with olaparib alone). In Study 7 (N = 59; 17 male, 42 female), 56 and 53 patients were evaluable for PK analysis following treatment with olaparib alone and olaparib plus itraconazole, respectively; in Study 8 (N = 22; 4 male, 18 female), all patients were evaluable. Co-administration of olaparib with itraconazole resulted in a statistically significant increase in the relative bioavailability of olaparib: Cmax treatment ratio, 1.42 (90% CI, 1.33-1.52); mean AUC treatment ratio, 2.70 (90% CI, 2.44-2.97). Mean CL/F and Vz/F were reduced (8.16 vs 3.05 L/h and 192 vs 75.1 L), although mean t½ was unchanged (15.0 vs 15.6 hours). Co-administration of olaparib with rifampin resulted in a statistically significant decrease in the relative bioavailability of olaparib: Cmax treatment ratio, 0.29 (90% CI, 0.24-0.33); mean AUC treatment ratio, 0.13 (90% CI, 0.11-0.16). CL/F and Vz/F were increased when olaparib and

  6. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial.

    Science.gov (United States)

    Swisher, Elizabeth M; Lin, Kevin K; Oza, Amit M; Scott, Clare L; Giordano, Heidi; Sun, James; Konecny, Gottfried E; Coleman, Robert L; Tinker, Anna V; O'Malley, David M; Kristeleit, Rebecca S; Ma, Ling; Bell-McGuinn, Katherine M; Brenton, James D; Cragun, Janiel M; Oaknin, Ana; Ray-Coquard, Isabelle; Harrell, Maria I; Mann, Elaina; Kaufmann, Scott H; Floquet, Anne; Leary, Alexandra; Harding, Thomas C; Goble, Sandra; Maloney, Lara; Isaacson, Jeff; Allen, Andrew R; Rolfe, Lindsey; Yelensky, Roman; Raponi, Mitch; McNeish, Iain A

    2017-01-01

    Poly(ADP-ribose) polymerase (PARP) inhibitors have activity in ovarian carcinomas with homologous recombination deficiency. Along with BRCA1 and BRCA2 (BRCA) mutations genomic loss of heterozygosity (LOH) might also represent homologous recombination deficiency. In ARIEL2, we assessed the ability of tumour genomic LOH, quantified with a next-generation sequencing assay, to predict response to rucaparib, an oral PARP inhibitor. ARIEL2 is an international, multicentre, two-part, phase 2, open-label study done at 49 hospitals and cancer centres in Australia, Canada, France, Spain, the UK, and the USA. In ARIEL2 Part 1, patients with recurrent, platinum-sensitive, high-grade ovarian carcinoma were classified into one of three predefined homologous recombination deficiency subgroups on the basis of tumour mutational analysis: BRCA mutant (deleterious germline or somatic), BRCA wild-type and LOH high (LOH high group), or BRCA wild-type and LOH low (LOH low group). We prespecified a cutoff of 14% or more genomic LOH for LOH high. Patients began treatment with oral rucaparib at 600 mg twice per day for continuous 28 day cycles until disease progression or any other reason for discontinuation. The primary endpoint was progression-free survival. All patients treated with at least one dose of rucaparib were included in the safety analyses and all treated patients who were classified were included in the primary endpoint analysis. This trial is registered with ClinicalTrials.gov, number NCT01891344. Enrolment into ARIEL2 Part 1 is complete, although an extension (Part 2) is ongoing. 256 patients were screened and 206 were enrolled between Oct 30, 2013, and Dec 19, 2014. At the data cutoff date (Jan 18, 2016), 204 patients had received rucaparib, with 28 patients remaining in the study. 192 patients could be classified into one of the three predefined homologous recombination deficiency subgroups: BRCA mutant (n=40), LOH high (n=82), or LOH low (n=70). Tumours from 12 patients

  7. Low-dose total skin electron beam therapy as a debulking agent for cutaneous T-cell lymphoma: an open-label prospective phase II study

    DEFF Research Database (Denmark)

    Kamstrup, Maria Rørbæk; Lindahl, L M; Gniadecki, Robert

    2011-01-01

    Background: Total skin electron beam therapy (TSEBT) is a powerful treatment for cutaneous T-cell lymphomas (CTCL). Based on the occurrence of relapses with low radiation doses, doses of 30-36 Gy are commonly used but most patients still eventually relapse and repeat treatment courses are limited...... due to the cumulative toxicity. Complete response rates are about 60-90% for T2-4 stages with a 5-year relapse-free survival of 10-25% for stages IB-III. Objectives: To evaluate prospectively the efficacy of low-dose TSEBT (10 Gy) in terms of complete cutaneous response rate, overall response rate...... and response duration in CTCL. Methods: Ten patients with stage IB-IV mycosis fungoides (MF) were treated in an open-label manner with 4 fractions of 1 Gy/week TSEB to a total skin dose of 10 Gy. Treatment responses were assessed at 1 and 3 months after treatment and subsequently at least every 6 months...

  8. Adjuvant capecitabine plus bevacizumab versus capecitabine alone in patients with colorectal cancer (QUASAR 2): an open-label, randomised phase 3 trial.

    Science.gov (United States)

    Kerr, Rachel S; Love, Sharon; Segelov, Eva; Johnstone, Elaine; Falcon, Beverly; Hewett, Peter; Weaver, Andrew; Church, David; Scudder, Claire; Pearson, Sarah; Julier, Patrick; Pezzella, Francesco; Tomlinson, Ian; Domingo, Enric; Kerr, David J

    2016-11-01

    Antiangiogenic agents have established efficacy in the treatment of metastatic colorectal cancer. We investigated whether bevacizumab could improve disease-free survival in the adjuvant setting after resection of the primary tumour. For the open-label, randomised, controlled QUASAR 2 trial, which was done at 170 hospitals in seven countries, we recruited patients aged 18 years or older with WHO performance status scores of 0 or 1 who had undergone potentially curative surgery for histologically proven stage III or high-risk stage II colorectal cancer. Patients were randomly assigned (1:1) to receive eight 3-week cycles of oral capecitabine alone (1250 mg/m(2) twice daily for 14 days followed by a break for 7 days) or the same regimen of oral capecitabine plus 16 cycles of 7·5 mg/kg bevacizumab by intravenous infusion over 90 min on day 1 of each cycle. Randomisation was done by a computer-generated schedule with use of minimisation with a random element stratified by age, disease stage, tumour site, and country. The study was open label and no-one was masked to treatment assignment. The primary endpoint was 3-year disease-free survival, assessed in the intention-to-treat population. Toxic effects were assessed in patients who received at least one dose of randomised treatment. This trial is registered with the ISRCTN registry, number ISRCTN45133151. Between April 25, 2005, and Oct 12, 2010, 1952 eligible patients were enrolled, of whom 1941 had assessable data (968 in the capecitabine alone group and 973 in the capecitabine and bevacizumab group). Median follow-up was 4·92 years (IQR 4·00-5·16). Disease-free survival at 3 years did not differ between the groups (75·4%, 95% CI 72·5-78·0 in the capecitabine and bevacizumab group vs 78·4%, 75·7-80·9 in the capecitabine alone group; hazard ratio 1·06, 95% CI 0·89-1·25, p=0·54). The most common grade 3-4 adverse events were hand-foot syndrome (201 [21%] of 963 in the capecitabine alone group vs 257 [27

  9. No evidence of harms of probiotic Lactobacillus rhamnosus GG ATCC 53103 in healthy elderly-a phase I open label study to assess safety, tolerability and cytokine responses.

    Directory of Open Access Journals (Sweden)

    Patricia L Hibberd

    Full Text Available BACKGROUND: Although Lactobacillus rhamnosus GG ATCC 53103 (LGG has been consumed by 2 to 5 million people daily since the mid 1990s, there are few clinical trials describing potential harms of LGG, particularly in the elderly. OBJECTIVES: The primary objective of this open label clinical trial is to assess the safety and tolerability of 1×1010 colony forming units (CFU of LGG administered orally twice daily to elderly volunteers for 28 days. The secondary objectives were to evaluate the effects of LGG on the gastrointestinal microbiome, host immune response and plasma cytokines. METHODS: Fifteen elderly volunteers, aged 66-80 years received LGG capsules containing 1×1010 CFU, twice daily for 28 days and were followed through day 56. Volunteers completed a daily diary, a telephone call on study days 3, 7 and 14 and study visits in the Clinical Research Center at baseline, day 28 and day 56 to determine whether adverse events had occurred. Assessments included prompted and open-ended questions. RESULTS: There were no serious adverse events. The 15 volunteers had a total of 47 events (range 1-7 per volunteer, 39 (83% of which were rated as mild and 40% of which were considered related to consuming LGG. Thirty-one (70% of the events were expected, prompted symptoms while 16 were unexpected events. The most common adverse events were gastrointestinal (bloating, gas, and nausea, 27 rated as mild and 3 rated as moderate. In the exploratory analysis, the pro-inflammatory cytokine interleukin 8 decreased during LGG consumption, returning towards baseline one month after discontinuing LGG (p = 0.038 while there was no difference in other pro- or anti-inflammatory plasma cytokines. CONCLUSIONS: Lactobacillus rhamnosus GG ATCC 53103 is safe and well tolerated in healthy adults aged 65 years and older. TRIAL REGISTRATION: ClinicalTrials.gov NCT 01274598.

  10. A Phase II Multicentre, Open-Label, Proof-of-Concept Study of Tasquinimod in Hepatocellular, Ovarian, Renal Cell, and Gastric Cancers.

    Science.gov (United States)

    Escudier, Bernard; Faivre, Sandrine; Van Cutsem, Eric; Germann, Nathalie; Pouget, Jean-Christophe; Plummer, Ruth; Vergote, Ignace; Thistlethwaite, Fiona; Bjarnason, Georg A; Jones, Robert; Mackay, Helen; Edeline, Julien; Fartoux, Laetitia; Hirte, Hal; Oza, Amit

    2017-08-10

    Tasquinimod is a small molecule with immunomodulatory, anti-angiogenic, and anti-metastatic properties that targets the tumor microenvironment. This study aimed to obtain a clinical proof of concept that tasquinimod was active and tolerable in patients with advanced solid tumors. This early stopping design, open-label, proof-of-concept clinical trial evaluated the clinical activity of tasquinimod in four independent cohorts of patients with advanced hepatocellular (n = 53), ovarian (n = 55), renal cell (n = 38), and gastric (n = 21) cancers. Tasquinimod was given orally every day (0.5 mg/day for at least 2 weeks, with dose increase to 1 mg/day) until radiological progression according to Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 criteria, intolerable toxicity, or patient withdrawal. The primary efficacy endpoint was progression-free survival (PFS) rate according to RECIST 1.1 by central assessment. Interim futility analyses at 8 weeks (6 weeks for the gastric cancer cohort) found adequate clinical activity of tasquinimod only in the hepatocellular cohort and recruitment to the other three cohorts was stopped. PFS rates were 26.9% at 16 weeks, 7.3% at 24 weeks, 13.2% at 16 weeks, and 9.5% at 12 weeks, respectively, in hepatocellular, ovarian, renal cell, and gastric cancer cohorts. The pre-defined PFS threshold was not reached in the hepatocellular cancer cohort at the second stage of the trial. The most common treatment-related adverse events were fatigue (48.5%), nausea (34.1%), decreased appetite (31.7%), and vomiting (24.6%). This study failed to demonstrate clinical activity of tasquinimod in heavily pre-treated patients with advanced hepatocellular, ovarian, renal cell, and gastric cancer. NCT01743469.

  11. Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial.

    Science.gov (United States)

    Baharoglu, M Irem; Cordonnier, Charlotte; Al-Shahi Salman, Rustam; de Gans, Koen; Koopman, Maria M; Brand, Anneke; Majoie, Charles B; Beenen, Ludo F; Marquering, Henk A; Vermeulen, Marinus; Nederkoorn, Paul J; de Haan, Rob J; Roos, Yvo B

    2016-06-25

    Platelet transfusion after acute spontaneous primary intracerebral haemorrhage in people taking antiplatelet therapy might reduce death or dependence by reducing the extent of the haemorrhage. We aimed to investigate whether platelet transfusion with standard care, compared with standard care alone, reduced death or dependence after intracerebral haemorrhage associated with antiplatelet therapy use. We did this multicentre, open-label, masked-endpoint, randomised trial at 60 hospitals in the Netherlands, UK, and France. We enrolled adults within 6 h of supratentorial intracerebral haemorrhage symptom onset if they had used antiplatelet therapy for at least 7 days beforehand and had a Glasgow Coma Scale score of at least 8. With use of a secure web-based system that concealed allocation and used biased coin randomisation, study collaborators randomly assigned participants (1:1; stratified by hospital and type of antiplatelet therapy) to receive either standard care or standard care with platelet transfusion within 90 min of diagnostic brain imaging. Participants and local investigators giving interventions were not masked to treatment allocation, but allocation was concealed from outcome assessors and investigators analysing data. The primary outcome was shift towards death or dependence rated on the modified Rankin Scale (mRS) at 3 months, and analysed by ordinal logistic regression, adjusted for stratification variables and the Intracerebral Haemorrhage Score. The primary analysis was done in the intention-to-treat population and safety analyses were done in the intention-to-treat and as-treated populations. This trial is registered with the Netherlands Trial Register, number NTR1303, and is now closed. Between Feb 4, 2009, and Oct 8, 2015, 41 sites enrolled 190 participants. 97 participants were randomly assigned to platelet transfusion and 93 to standard care. The odds of death or dependence at 3 months were higher in the platelet transfusion group than in the

  12. Intravenous pamidronate versus oral and intravenous clodronate in bone metastatic breast cancer: a randomized, open-label, non-inferiority Phase III trial

    Directory of Open Access Journals (Sweden)

    von Au A

    2016-07-01

    Full Text Available Alexandra von Au,1 Eva Milloth,1 Ingo Diel,2 Stefan Stefanovic,1 Andre Hennigs,1 Markus Wallwiener,1 Joerg Heil,1 Michael Golatta,1 Joachim Rom,1 Christof Sohn,1 Andreas Schneeweiss,1 Florian Schuetz,1 Christoph Domschke1 1Breast Unit, Department of Gynecology and Obstetrics, Heidelberg University Hospital, Heidelberg, 2CGG Clinic – Centrum für ganzheitliche Gynäkologie Mannheim, Mannheim, Germany Purpose: Patients with metastasized breast cancer often suffer from discomfort caused by metastatic bone disease. Thus, osteoprotection is an important part of therapy in breast cancer metastasized to bone, and bisphosphonates (BPs are a major therapeutic option. In this study, our objectives were to compare the side effects of oral versus intravenous BP treatment and to assess their clinical effectiveness.  Patients and methods: In this prospective randomized, open-label, non-inferiority trial, we enrolled breast cancer patients with at least one bone metastasis and an Eastern Cooperative Oncology Group performance status of 0–2. Patients were randomly assigned to one of the three treatment groups: A, 60 mg pamidronate intravenously q3w; B-iv, 900 mg clodronate intravenously q3w; and B-o, 2,400 mg oral clodronate daily. Assessments were performed at baseline and every 3 months thereafter.  Results: Between 1995 and 1999, 321 patients with confirmed bone metastases from breast cancer were included in the study. At first follow-up, gastrointestinal (GI tract side effects were most common, and adverse effects on the GI tract were more frequent in the oral treatment group (P=0.002 and P<0.001, respectively. There were no statistically significant differences among the treatment cohorts for other documented side effects (skin, serum electrolytes, urinary tract, immune system, and others. No significant differences in clinical effectiveness of BP treatment, as assessed by pain score, were detected among the groups; however, pathologic fractures

  13. Enzyme replacement therapy for mucopolysaccharidosis VI: a phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study.

    Science.gov (United States)

    Harmatz, Paul; Giugliani, Roberto; Schwartz, Ida; Guffon, Nathalie; Teles, Elisa Leão; Miranda, M Clara Sá; Wraith, J Edmond; Beck, Michael; Arash, Laila; Scarpa, Maurizio; Yu, Zi-Fan; Wittes, Janet; Berger, Kenneth I; Newman, Mary S; Lowe, Ann M; Kakkis, Emil; Swiedler, Stuart J

    2006-04-01

    The objective of this Phase 3 study was to confirm the efficacy and safety of recombinant human arylsulfatase B (rhASB) treatment of mucopolysaccharidosis type VI (MPS VI; Maroteaux-Lamy syndrome), a rare, fatal lysosomal storage disease with no effective treatment. Thirty-nine patients with MPS VI were evaluated in a randomized, double-blind, placebo-controlled, multicenter, multinational study for 24 weeks. The primary efficacy variable was the distance walked in a 12-minute walk test (12MWT), whereas the secondary efficacy variables were the number of stairs climbed in a 3-minute stair climb (3MSC) and the level of urinary glycosaminoglycan (GAG) excretion. All patients received drug in an open-label extension period for an additional 24 weeks. After 24 weeks, patients receiving rhASB walked on average 92 meters (m) more in the 12MWT (p=.025) and 5.7 stairs per minute more 3MSC (p=.053) than patients receiving placebo. Continued improvement was observed during the extension study. Urinary GAG declined by -227+/-18 microg/mg more with rhASB than placebo (p<.001). Infusions were generally safe and well tolerated. Patients exposed to drug experienced positive clinical benefit despite the presence of antibody to the protein. rhASB significantly improves endurance, reduces GAG, and has an acceptable safety profile.

  14. Safety and pharmacokinetic profile of rufinamide in pediatric patients aged less than 4 years with Lennox-Gastaut syndrome: An interim analysis from a multicenter, randomized, active-controlled, open-label study.

    Science.gov (United States)

    Arzimanoglou, Alexis; Ferreira, Jose A; Satlin, Andrew; Mendes, Shannon; Williams, Betsy; Critchley, David; Schuck, Edgar; Hussein, Ziad; Kumar, Dinesh; Dhadda, Shobha; Bibbiani, Francesco

    2016-05-01

    A good knowledge of safety and age group-specific pharmacokinetics (PK) of antiepileptic drugs (AEDs) in young pediatric patients is of great importance in clinical practice. This paper presents 6-month interim safety and PK from an ongoing 2-year open-label study (Study 303) of adjunctive rufinamide treatment in pediatric subjects ≥ 1 to < 4 years with inadequately controlled epilepsies of the Lennox-Gastaut syndrome (LGS) spectrum. Subjects (N = 37) were randomized to either rufinamide or any other approved AED chosen by the investigator as adjunctive therapy to the subject's existing regimen of 1-3 AEDs. Interim safety results showed that treatment-emergent adverse events (TEAEs) were similar between the rufinamide (22 [88.0%]) and any-other-AED group (9 [81.8%]), with most events considered mild or moderate. A population PK analysis was conducted including plasma rufinamide concentrations from Study 303 and two other study populations of LGS subjects ≥ 4 years. The rufinamide PK profile was dose independent. The apparent clearance (CL/F) estimated from the PK model was 2.19 L/h; it was found to increase significantly as a function of body weight. Coadministration of valproic acid significantly decreased rufinamide CL/F. CL/F was not significantly affected by other concomitant AEDs, age, gender, race, hepatic function, or renal function. No adjustments to body weight-based rufinamide dosing in subjects ≥ 1 to < 4 years are necessary. Rufinamide was safe and well tolerated in these pediatric subjects. Results from the interim analysis demonstrate that rufinamide's safety and PK profile is comparable in subjects ≥ 1 to < 4 and ≥ 4 years with LGS. Study 303 (clinicaltrials.gov: NCT01405053). Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Adherence with ethinylestradiol 20 µg/drospirenone 3 mg in a flexible extended regimen supported by the use of a digital tablet dispenser with or without acoustic alarm: an open-label, randomized, multicenter study

    Directory of Open Access Journals (Sweden)

    Wiegratz I

    2015-01-01

    Full Text Available Inka Wiegratz,1,2 Jörg Elliesen,3 Anna Maria Paoletti,4 Anja Walzer,3 Bodo Kirsch3 1Kinderwunschpraxis am Goetheplatz, Frankfurt, Germany; 2MVZ Kinderwunschzentrum Wiesbaden GmbH, Wiesbaden, Germany; 3Bayer HealthCare Pharmaceuticals, Berlin, Germany; 4Clinica Ostetrica e Ginecologica, University of Cagliari, Cagliari, ItalyObjective: To evaluate the effect of a digital dispenser's acoustic alarm function on adherence to ethinylestradiol (EE 20 µg/drospirenone 3 mg in a flexible extended regimen (EE/drospirenoneFlex among women in five European countries (France, Germany, Italy, Spain, UK seeking oral contraception.Study design: Randomized, parallel-group open-label study.Methods: Women aged 18–35 years received EE/drospirenoneFlex administered in a regimen with cycle lengths of their choice with the aid of a digital pill dispenser over 1 year. In group A (N=250, the dispenser's acoustic alarm was activated (ie, acoustic alarm + visual reminder. In group B (N=249, the acoustic alarm was deactivated (ie, visual reminder only. In addition, the women recorded pill intake daily in diary cards. The primary efficacy variable was the mean delay of daily pill release after the dispenser reminded the woman to take a pill (reference time. Secondary efficacy variables included number of missed pills, contraceptive efficacy, bleeding pattern, tolerability, and user satisfaction.Results: Dispenser data showed a mean (standard deviation [SD] daily delay in pill release of 88 (126 minutes in group A vs 178 (140 minutes in group B (P<0.0001. Median (lower quartile, Q1; upper quartile, Q3 number of missed pills was 0 (0; 1 in group A vs 4 (1; 9 in group B (P<0.0001. Diary card results revealed similar trends; however, underreporting of missed pills was evident in both groups. No pregnancies were reported during 424 women-years of exposure. Across the two groups, the mean (SD EE/drospirenoneFlex cycle length was 51.0 (31.8 days with strong regional

  16. AN OPEN-LABEL MULTICENTER OBSERVATIONAL STUDY OF THE EFFICACY, TOLERABILITY, AND SAFETY OF THE NONSTEROIDAL ANTI-INFLAMMATORY DRUG AMTOLMETIN GUACIL IN PATIENTS WITH KNEE OSTEOARTHRITIS AND DYSPEPSIA

    Directory of Open Access Journals (Sweden)

    E. S. Tsvetkova

    2016-01-01

    Full Text Available Objective: to investigate the efficacy and tolerability of amtolmetin guacil (AMG; Niselat®, Dr. Reddy's Laboratories Ltd, India versus previous therapy with nonsteroidal anti-inflammatory drugs (NSAIDs in patients with knee osteoarthritis (OA and signs of dyspepsia.Subjects and methods. The open-label observational study included 220 patients aged 30–65 years who suffered from knee OA and intense pain during NSAID intake and had symptoms of dyspepsia in the absence of contraindications to the use of AMG. Among the comorbidities that generally occurred in 68% of the patients, there was a preponderance of hypertension (42%, lower extremity varicose veins (6.4%, and diabetes mellitus (6%. Treatment efficacy was evaluated using three domains of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC, by also taking into account pain intensity and general health assessment on the visual analogue scale. A Severity of Dyspepsia Assessment (SODA scale was used to rate dyspepsia.Results and discussion. AMG had a marked analgesic effect confirmed by 40% or more pain reduction that occurred in 72.5% of the patients. The high analgesic effect of AMG was confirmed by a statistically significant (p <0.001 reduction in the WOMAC index (pain and stiffness and by an increase in functional activity. There was a significant decrease in painless and painful signs of dyspepsia, as well as positive changes in the measures “overall assessment of dyspepsia severity” (p < 0.001 and “satisfaction with treatment”. Overall assessment of AMG tolerability was only positive: excellent (33%, good (56%, and satisfactory (11%. There were no serious adverse events (AE. AE were graded as moderate and mild in 8 and 82% of cases, respectively. AE were recorded in 7.7% of the patients. Conclusion. The findings suggest that AMG offers good prospects for knee OA treatment.

  17. A Phase 1 Randomized, Open Label, Rectal Safety, Acceptability, Pharmacokinetic, and Pharmacodynamic Study of Three Formulations of Tenofovir 1% Gel (the CHARM-01 Study.

    Directory of Open Access Journals (Sweden)

    Ian Mcgowan

    Full Text Available The CHARM-01 study characterized the safety, acceptability, pharmacokinetics (PK, and pharmacodynamics (PD of three tenofovir (TFV gels for rectal application. The vaginal formulation (VF gel was previously used in the CAPRISA 004 and VOICE vaginal microbicide Phase 2B trials and the RMP-02/MTN-006 Phase 1 rectal safety study. The reduced glycerin VF (RGVF gel was used in the MTN-007 Phase 1 rectal microbicide trial and is currently being evaluated in the MTN-017 Phase 2 rectal microbicide trial. A third rectal specific formulation (RF gel was also evaluated in the CHARM-01 study.Participants received 4 mL of the three TFV gels in a blinded, crossover design: seven daily doses of RGVF, seven daily doses of RF, and six daily doses of placebo followed by one dose of VF, in a randomized sequence. Safety, acceptability, compartmental PK, and explant PD were monitored throughout the trial.All three gels were found to be safe and acceptable. RF and RGVF PK were not significantly different. Median mucosal mononuclear cell (MMC TFV-DP trended toward higher values for RF compared to RGVF (1136 and 320 fmol/106 cells respectively. Use of each gel in vivo was associated with significant inhibition of ex vivo colorectal tissue HIV infection. There was also a significant negative correlation between the tissue levels of TFV, tissue TFV-DP, MMC TFV-DP, rectal fluid TFV, and explant HIV-1 infection.All three formulations were found to be safe and acceptable. However, the safety profile of the VF gel was only based on exposure to one dose whereas participants received seven doses of the RGVF and RF gels. There was a trend towards higher tissue MMC levels of TFV-DP associated with use of the RF gel. Use of all gels was associated with significant inhibition of ex vivo tissue HIV infection.ClinicalTrials.gov NCT01575405.

  18. Results of a phase II, open-label, non-comparative study of intralesional PV-10 followed by radiotherapy for the treatment of in-transit or metastatic melanoma.

    Science.gov (United States)

    Foote, Matthew; Read, Tavis; Thomas, Janine; Wagels, Michael; Burmeister, Bryan; Smithers, B Mark

    2017-06-01

    In-transit and recurrent dermal or subcutaneous melanoma metastases represent a significant burden of advanced disease. Intralesional Rose Bengal can elicit tumor selective ablation and a T-cell mediated abscopal effect in untreated lesions. A subset of patients in a phase II trial setting received external beam radiotherapy to their recurrent lesions with complete or partial response and no significant acute radiation reaction. An open-label, single-arm phase II study was performed to assess the efficacy and safety of PV-10 followed by hypofractionated radiotherapy. Patients had in-transit melanoma metastases suitable for IL therapy and radiotherapy. Fifteen patients were enrolled and thirteen completed both treatment components. The overall response rate was 86.6% and the clinical benefit was 93.3% on an intention to treat analysis (CR 33.3%, PR 53.3%, SD 6.7%). The median follow up duration was 19.25 months. Size of metastases (Treatment was well tolerated with no associated grade 4 or 5 adverse events. The combination of PV-10 and radiotherapy resulted in lesion-specific, normal tissue-sparing, ablation of disease with minimal local or systemic adverse effects. © 2017 Wiley Periodicals, Inc.

  19. A multicenter phase II study of irinotecan in patients with advanced colorectal cancer previously treated with 5-fluorouracil.

    Science.gov (United States)

    Méndez, Miguel; Salut, Antonieta; García-Girón, Carlos; Navalon, Marta; Diz, Pilar; García López, Maria José; España, Pilar; de la Torre, Ascensión; Martínez del Prado, Purificación; Duarte, Isabel; Pujol, Eduardo; Arizcun, Alberto; Cruz, Juan Jesús

    2003-11-01

    This multicenter, open-label, phase II study was performed to assess the efficacy and toxicity of irinotecan 350 mg/m2 intravenously every 3 weeks in patients with advanced colorectal cancer (CRC) previously treated with 5-fluorouracil (5-FU). The study enrolled 115 patients and a total of 558 cycles (median, 6 per patient) were administered. The overall objective response rate on an intent-to-treat basis was 18% (with 1 complete response and 20 partial responses), whereas 42 patients (37%) showed stable disease. Median time to progression was 4.8 months and median survival was 13.6 months. Grade 3/4 toxicities included delayed diarrhea (19.1%), nausea/vomiting (10.4%), and neutropenia (8.7%). There were 2 toxic deaths, 1 from delayed diarrhea and 1 from hemorrhage and grade 4 mucositis. In conclusion, the present study confirms the antitumor efficacy of irinotecan monotherapy in patients with CRC pretreated with 5-FU.

  20. Reduction of the morning blood pressure surge treated with olmesartan in Chinese patients with mild to moderate essential hypertension--a multicenter, open-label, single treatment group clinical study.

    Science.gov (United States)

    Jiao, Yuan; Ke, Yuannan; Sun, Ningling; Wang, Jiguang; Deng, Wude; Zhu, Junren

    2012-05-01

    To investigate the morning blood pressure surge (MBPS) in Chinese patients with mild to moderate essential hypertension treated with long-term administration of olmesartan, an angiotensin II receptor antagonist according to ambulatory blood pressure monitoring (ABPM). In a multi-center, prospective study, we investigated the long-term efficacy of olmesartan by ABPM in 18-75 years-old Chinese patients with mild to moderate hypertension (clinic diastolic blood pressure [DBP] 90-109 mm Hg and systolic blood pressure [SBP] olmesartan 20 mg once daily in the morning for 24 weeks. Ambulatory blood pressure monitoring was conducted at baseline and at the end of 24 weeks. At baseline, patients with an MBPS > or = 23 mmHg were classified as the MBPS group (n = 41), and all other patients were classified as the non-MBPS group (n = 46). The mean systolic and diastolic blood pressures (SBP/DBP) over 24 hours were reduced from 141.78 +/- 12.8/91.17 +/- 7.34 to 128.35 +/- 15.86/83.58 +/- 9.53 mmHg (p olmesartan were significantly different between the two groups (p Olmesartan effectively reduces blood pressure in patients with essential hypertension, and olmesartan especially reduces the MBPS in MBPS-prone patients.

  1. A study from the EORTC new drug development group: open label phase II study of sabarubicin (MEN-10755) in patients with progressive hormone refractory prostate cancer.

    Science.gov (United States)

    Fiedler, W; Tchen, N; Bloch, J; Fargeot, P; Sorio, R; Vermorken, J B; Collette, L; Lacombe, D; Twelves, C

    2006-01-01

    Sabarubicin (MEN-10755), a new synthetic anthracycline analogue, was evaluated for safety and efficacy in a multicentre phase II study in patients with advanced hormone refractory prostate cancer (HRPC). Thirty seven patients were included, of which 34 were evaluable for PSA response according to Bubley's criteria. Sabarubicin was administered as a short (30 min) intravenous infusion at a dose of 80 mg/m(2) every 3 weeks. The main toxicity consisted of grade 3/4 neutropenia in 24 patients (64.9%), with grade 3/4 febrile neutropenia occurring in one patient only. Grade 3/4 cardiotoxicity was observed in 4 patients including one ineligible. Other toxicities were mild. Nine patients achieved a PSA response (26.5%), 10 patients had stable disease (29.4%) and 14 patients disease progression (41.2%). One patient (2.9%) had a PSA response that was not confirmed by repeat PSA testing. The objective response rate according to RECIST criteria was 6.7% in 15 patients with measurable disease. The median duration of PSA responses was relatively long 7.1 months (95% CI 4.9-20.7) as was the median time to treatment progression in patients with stable disease. The median overall survival was 18.7 months (95% CI 9.1-N), comparable to results recently observed in taxotere-containing regimens. To confirm and extend these results, further testing of sabarubicin in larger trials is warranted.

  2. A six-month, multicenter, open-label, noncomparative, prospective, observational study of the efficacy and tolerability of atorvastatin in the primary care setting(estudio del control de las hiperlipidemiasen atención primaria): the cheap study.

    Science.gov (United States)

    Gómez-Gerique, Juan A; Alvarez-Sala, Luis A; Armada, Beatriz; Fernández-Arias, Isabel; Martinez, Javier; Hernández, Gonzalo

    2003-06-01

    A close relationship exists between high levels of total cholesterol (TC) (particularly low-density lipoprotein cholesterol [LDL-C]) and low levels of high-density lipoprotein cholesterol (HDL-C), which is associated with an increased risk for arteriosclerosis and cardiovascular disease (CVD). Evidence shows that atorvastatin produces significantly greater reductions in LDL-C and TC than other hydroxymethylglutaryl-coenzyme A reductase inhibitors. However, the results achieved in clinical studies could be different from those found in general clinical practice, where patient follow-up is less thorough and poorer compliance may reduce the effectiveness of the lipid-lowering therapy. The aim of this study was to assess the effectiveness of atorvastatin in achieving the LDL-C levels recommended by several Spanish scientific societies, as well as its tolerability in standard clinical use. This 6-month, open-label, noncomparative, prospective, observational study was conducted in 1351 primary care centers in Spain. All patients were aged 18 to 80 years and had primary hypercholesterolemia (TC >200 mg/dL and triglycerides [TG] 200 mg/dL and fasting TG 200-400 mg/dL). All patients also had LDL-C levels higher than those established by the Spanish Society of Arteriosclerosis (Sociedad Española de Arteriosclerosis [SEA]) according to baseline cardiovascular risk and previous use of lipid-lowering therapy (for patients with low, moderate, or high cardiovascular risk, the recommended LDL-C goals are ≤175 mg/dL, ≤155 mg/dL, and ≤135 mg/dL, respectively; for patients with CVD, the LDL-C goal is ≤100 mg/dL). None of the patients had creatine kinase activity ≥540 U/L or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ≥60 U/L. Study visits occurred at months 0, 2, and 6 of treatment. Patients received atorvastatin calcium 10 mg/d for 2 months. The dosage was then doubled to 20 mg/d in patients who did not achieve the SEA LDL-C goal and also

  3. Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1-2 study.

    Science.gov (United States)

    Perl, Alexander E; Altman, Jessica K; Cortes, Jorge; Smith, Catherine; Litzow, Mark; Baer, Maria R; Claxton, David; Erba, Harry P; Gill, Stan; Goldberg, Stuart; Jurcic, Joseph G; Larson, Richard A; Liu, Chaofeng; Ritchie, Ellen; Schiller, Gary; Spira, Alexander I; Strickland, Stephen A; Tibes, Raoul; Ustun, Celalettin; Wang, Eunice S; Stuart, Robert; Röllig, Christoph; Neubauer, Andreas; Martinelli, Giovanni; Bahceci, Erkut; Levis, Mark

    2017-08-01

    Internal tandem duplication mutations in FLT3 are common in acute myeloid leukaemia and are associated with rapid relapse and short overall survival. The clinical benefit of FLT3 inhibitors in patients with acute myeloid leukaemia has been limited by rapid generation of resistance mutations, particularly in codon Asp835 (D835). We aimed to assess the highly selective oral FLT3 inhibitor gilteritinib in patients with relapsed or refractory acute myeloid leukaemia. In this phase 1-2 trial, we enrolled patients aged 18 years or older with acute myeloid leukaemia who either were refractory to induction therapy or had relapsed after achieving remission with previous treatment. Patients were enrolled into one of seven dose-escalation or dose-expansion cohorts assigned to receive once-daily doses of oral gilteritinib (20 mg, 40 mg, 80 mg, 120 mg, 200 mg, 300 mg, or 450 mg). Cohort expansion was based on safety and tolerability, FLT3 inhibition in correlative assays, and antileukaemic activity. Although the presence of an FLT3 mutation was not an inclusion criterion, we required ten or more patients with locally confirmed FLT3 mutations (FLT3(mut+)) to be enrolled in expansion cohorts at each dose level. On the basis of emerging findings, we further expanded the 120 mg and 200 mg dose cohorts to include FLT3(mut+) patients only. The primary endpoints were the safety, tolerability, and pharmacokinetics of gilteritinib. Safety and tolerability were assessed in the safety analysis set (all patients who received at least one dose of gilteritinib). Responses were assessed in the full analysis set (all patients who received at least one dose of study drug and who had at least one datapoint post-treatment). Pharmacokinetics were assessed in a subset of the safety analysis set for which sufficient data for concentrations of gilteritinib in plasma were available to enable derivation of one or more pharmacokinetic variables. This study is registered with ClinicalTrials.gov, number

  4. Atomoxetine Open-Label Trial in ADHD

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2002-07-01

    Full Text Available Atomoxetine (originally named tomoxetine, a new therapy for attention deficit hyperactivity disorder (ADHD marketed by Eli Lilly, was compared to methylphenidate in a prospective, randomized, open-label study for 10 weeks duration, at the University of Nebraska Medical Center, Massachusetts General Hospital, Mount Sinai Medical Center, Carolinas Medical Center, and Lilly Research Laboratories.

  5. Evaluation on the efficacy and safety of Chinese herbal medication Xifeng Dingchan Pill in treating Parkinson's disease: study protocol of a multicenter,open-label, randomized active-controlled trial

    Institute of Scientific and Technical Information of China (English)

    Jie Zhang; Yun-zhi Ma; Xiao-ming Shen

    2013-01-01

    BACKGROUND:Parkinson's disease (PD) is a complicated disease,commonly diagnosed among the elderly,which leads to degeneration of the central nervous system.It presently lacks an effective therapy for its complex pathogenesis.Adverse effects from Western drug-based medical intervention prevent long-term adherence to these therapies in many patients.Traditional Chinese medicine (TCM) has long been used to improve the treatment of PD by alleviating the toxic and adverse effects of Western drug-based intervention.Therefore,the aim of this study is to evaluate the efficacy and safety of Xifeng Dingchan Pill (XFDCP),a compound traditional Chinese herbal medicine,taken in conjunction with Western medicine in the treatment of PD patients at different stages in the progression of the disease.METHODS AND DESIGN:This is a multicenter,randomized controlled trial.In total,320 patients with early-(n =160) and middle-stage PD (n =160) will be enrolled and divided evenly into control and trial groups.Of the 160 patients with early-stage PD,the trial group (n =80) will be given XFDCP,and the control group (n =80) will be given Madopar.Of the 160 patients with middle-stage PD,the trial group (n =80) will be given XFDCP combined with Madopar and Piribedil,and the control group (n =80) will be given Madopar and Piribedil.The Unified Parkinson's Disease Rating Scale scores,TCM symptoms scores,quality of life,change of Madopar's dosage and the toxic and adverse effects of Madopar will be observed during a 3-month treatment period and through a further 6-month follow-up period.DISCUSSION:It is hypothesized that XFDCP,combined with Madopar and Piribedil,will have beneficial effects on patients with PD.The results of this study will provide evidence for developing a comprehensive therapy regimen,which can delay the progress of the disease and improve the quality of life for PD patients in different stages.TRIAL REGISTRATION:This trial has been registered in the Chinese Clinical Trial

  6. Carfilzomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed multiple myeloma: a multicenter, phase 2 study.

    Science.gov (United States)

    Bringhen, Sara; Petrucci, Maria Teresa; Larocca, Alessandra; Conticello, Concetta; Rossi, Davide; Magarotto, Valeria; Musto, Pellegrino; Boccadifuoco, Luana; Offidani, Massimo; Omedé, Paola; Gentilini, Fabiana; Ciccone, Giovannino; Benevolo, Giulia; Genuardi, Mariella; Montefusco, Vittorio; Oliva, Stefania; Caravita, Tommaso; Tacchetti, Paola; Boccadoro, Mario; Sonneveld, Pieter; Palumbo, Antonio

    2014-07-03

    This multicenter, open-label phase 2 trial determined the safety and efficacy of carfilzomib, a novel and irreversible proteasome inhibitor, in combination with cyclophosphamide and dexamethasone (CCyd) in patients with newly diagnosed multiple myeloma (NDMM) ≥65 years of age or who were ineligible for autologous stem cell transplantation. Patients (N = 58) received CCyd for up to 9 28-day cycles, followed by maintenance with carfilzomib until progression or intolerance. After a median of 9 CCyd induction cycles (range 1-9), 95% of patients achieved at least a partial response, 71% achieved at least a very good partial response, 49% achieved at least a near complete response, and 20% achieved stringent complete response. After a median follow-up of 18 months, the 2-year progression-free survival and overall survival rates were 76% and 87%, respectively. The most frequent grade 3 to 5 toxicities were neutropenia (20%), anemia (11%), and cardiopulmonary adverse events (7%). Peripheral neuropathy was limited to grades 1 and 2 (9%). Fourteen percent of patients discontinued treatment because of adverse events, and 21% of patients required carfilzomib dose reductions. In summary, results showed high complete response rates and a good safety profile. This trial was registered at clinicaltrials.gov as #NCT01346787.

  7. Simeprevir in combination with sofosbuvir in treatment-naïve and -experienced patients with hepatitis C virus genotype 4 infection: a Phase III, open-label, single-arm study (PLUTO).

    Science.gov (United States)

    Buti, M; Calleja, J L; Lens, S; Diago, M; Ortega, E; Crespo, J; Planas, R; Romero-Gómez, M; Rodríguez, F G; Pascasio, J M; Fevery, B; Kurland, D; Corbett, C; Kalmeijer, R; Jessner, W

    2017-02-01

    Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and subsequent hepatocellular carcinoma. HCV genotype 4 is found widely in the Middle East, Egypt and Africa, and has also spread into Europe. There are limited data available regarding the use of direct-acting antiviral agents in HCV genotype 4-infected patients with cirrhosis. To evaluate in the phase III, open-label, single-arm PLUTO study the efficacy and safety of 12 weeks of simeprevir (HCV NS3/4A protease inhibitor) plus sofosbuvir (HCV nucleotide-analogue NS5B polymerase inhibitor) in treatment-naïve and (peg)interferon ± ribavirin-experienced HCV genotype 4-infected patients, with or without compensated cirrhosis. Adult patients with chronic HCV genotype 4 infection received simeprevir 150 mg once-daily and sofosbuvir 400 mg once-daily for 12 weeks. The primary efficacy endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). Safety was also assessed. Forty patients received treatment; the majority were male (73%) and treatment-experienced (68%). Overall, 7/40 (18%) patients had compensated cirrhosis. All patients achieved SVR12 [100% (Clopper-Pearson 95% confidence interval: 91-100%)]. Adverse events, all Grade 1 or 2, were reported in 20/40 (50%) patients. No serious adverse events were reported and no patients discontinued study treatment. Grade 3 treatment-emergent laboratory abnormalities were noted in 2/40 (5%) patients. Treatment with simeprevir plus sofosbuvir for 12 weeks resulted in SVR12 rates of 100% in treatment-naïve and -experienced patients with HCV genotype 4 infection with or without compensated cirrhosis, and was well tolerated. [NCT02250807]. © 2016 John Wiley & Sons Ltd.

  8. A Phase III, randomized, open-label trial of ferumoxytol compared with iron sucrose for the treatment of iron deficiency anemia in patients with a history of unsatisfactory oral iron therapy.

    Science.gov (United States)

    Hetzel, David; Strauss, William; Bernard, Kristine; Li, Zhu; Urboniene, Audrone; Allen, Lee F

    2014-06-01

    Iron deficiency anemia (IDA) is the most common form of anemia worldwide. Although oral iron is used as first-line treatment, many patients are unresponsive to or cannot take oral iron. This Phase III, open-label, non-inferiority study compared the efficacy and safety of ferumoxytol, a rapid, injectable intravenous (IV) iron product with low immunological reactivity and minimal detectable free iron, with IV iron sucrose in adults with IDA of any cause. Patients (N = 605) were randomized 2:1 to receive ferumoxytol (n = 406, two doses of 510 mg 5 ± 3 days apart) or iron sucrose (n = 199, five doses of 200 mg on five nonconsecutive days over 14 days) and followed for 5 weeks. Ferumoxytol demonstrated noninferiority to iron sucrose at the primary endpoint, the proportion of patients achieving a hemoglobin increase of ≥2 g dL(-1) at any time from Baseline to Week 5 (ferumoxytol, 84.0% [n = 406] vs. iron sucrose, 81.4% [n = 199]), with a noninferiority margin of 15%. Ferumoxytol was superior to iron sucrose (2.7 g dL(-1) vs. 2.4 g dL(-1) ) in the mean change in hemoglobin from Baseline to Week 5 (the alternative preplanned primary endpoint) with P = 0.0124. Transferrin saturation, quality-of-life measures, and safety outcomes were similar between the two treatment groups. Overall, ferumoxytol demonstrated comparable safety and efficacy to iron sucrose, suggesting that ferumoxytol may be a useful treatment option for patients with IDA in whom oral iron was unsatisfactory or could not be used.

  9. An open label randomized multicentre phase IIIb trial comparing parenteral substitution versus best supportive nutritional care in subjects with pancreatic adenocarcinoma receiving 5-FU plus oxaliplatin as 2nd or higher line chemotherapy regarding clinical benefit - PANUSCO

    Directory of Open Access Journals (Sweden)

    Rötzer Ingeborg

    2009-11-01

    Full Text Available Abstract Background Pancreatic cancer is an extremely aggressive malignancy. Subjects are afflicted with a variety of disconcerting symptoms, including profound cachexia. Recent data indicate that the outcome of oncological patients suffering from cancer cachexia could be improved by parenteral nutrition and that parenteral nutrition results in an improvement of quality of life and in prolonged survival. Currently, there is no recommendation of routine use of parenteral nutrition. Furthermore, there is no clear recommendation for 2nd line therapy (or higher for pancreatic adenocarcinoma but often asked for. Methods/Design PANUSCO is an open label, controlled, prospective, randomized, multicentre phase IIIb trial with two parallel arms. All patients will be treated with 5-fluorouracil, folinic acid and oxaliplatin on an outpatient basis at the study sites. Additionally, all patients will receive best supportive nutritional care (BSNC. In the experimental group BSNC will be expanded with parenteral nutrition (PN. In contrast, patients in the control group obtain solely BSNC. Parenteral nutrition will be applied overnight and at home by experienced medical staff. A total of 120 patients are planned to be enrolled. Primary endpoint is the comparison of the treatment groups with respect to event-free survival (EFS, defined as the time from randomization till time to development of an event defined as either an impairment (change from baseline of at least ten points in EORTC QLQ-C30, functional domain total score or withdrawal due to fulfilling the special defined stopping criteria for chemotherapy as well as for nutritional intervention (NI or death from any cause (whichever occurs first. Discussion The aim of this clinical trial is to evaluate whether parenteral nutrition in combination with defined 2nd line or higher chemotherapy has an impact on quality of life for patients suffering from pancreatic adenocarcinoma. Trial registration Current

  10. PF-03446962, a fully-human monoclonal antibody against transforming growth-factor β (TGFβ) receptor ALK1, in pre-treated patients with urothelial cancer: an open label, single-group, phase 2 trial.

    Science.gov (United States)

    Necchi, A; Giannatempo, P; Mariani, L; Farè, E; Raggi, D; Pennati, M; Zaffaroni, N; Crippa, F; Marchianò, A; Nicolai, N; Maffezzini, M; Togliardi, E; Daidone, M G; Gianni, A M; Salvioni, R; De Braud, F

    2014-06-01

    Despite a compelling preclinical rationale for the use of anti-angiogenic drugs in urothelial cancer (UC), short-living responses have been observed in clinical trials. PF-03446962 is a novel monoclonal antibody against Activin Receptor-Like Kinase-1 (ALK1), a type I subclass of the TGFβ receptor, with dose-dependent anti-angiogenic activity. An open label, single-group, phase 2 trial of PF-03446962 was conducted in salvage setting. Patients failing at least one chemotherapy regimen were eligible. Design provided PF-03446962 10 mg/Kg intravenously fortnightly until disease progression (PD) or unacceptable toxicity. Two-month progression-free survival (PFS) was the primary endpoint. The trial was registered with ClinicalTrials.gov, number NCT01620970. Fourteen patients were enrolled from October 2012 to July 2013. Median age was 64 years (interquartile range [IQR]: 58.2-69.5), 9 patients had a Bellmunt score of 1-2, median number of prior drugs was 3. One stable disease and 13 PD were recorded and the study met the futility stopping rule of interim analysis. Median PFS was 1.8 months (95 %CI, 1.4-2.0). After a median follow up of 7.4 months (IQR 4.5-10.9), 8 patients are alive. Median overall survival (OS) was 8 months (95 %CI, 2.9-not estimable). Most common toxicities were thrombocytopenia (G1-2 in 5 cases, persistent G3 in one, with 3 dose delays and 1 dose interruption), fatigue and abdominal pain (G1-2 in 4 cases each). Impairment of quality of life (ESAS score) was observed as well as an increase from baseline to +2 month median levels of vascular endothelial growth factor (VEGF) and interleukin-8. PF-03446962 had no activity as single drug in refractory UC and we do not recommend further investigation outside of the combination with agents targeting the VEGF receptor axis.

  11. A Phase 1, Open-Label, Randomized, Crossover Study Evaluating the Bioavailability of TAS-102 (Trifluridine/Tipiracil) Tablets Relative to an Oral Solution Containing Equivalent Amounts of Trifluridine and Tipiracil.

    Science.gov (United States)

    Becerra, Carlos R; Yoshida, Kenichiro; Mizuguchi, Hirokazu; Patel, Manish; Von Hoff, Daniel

    2017-06-01

    TAS-102 (trifluridine/tipiracil) is composed of an antineoplastic thymidine-based nucleoside analogue trifluridine (FTD), and a thymidine phosphorylase inhibitor, tipiracil (TPI), at a molar ratio of 1:0.5 (weight ratio, 1:0.471). A phase 1 study evaluated relative bioavailability of TAS-102 tablets compared with an oral solution containing equivalent amounts of FTD and TPI. In an open-label, 2-sequence, 3-period, crossover bioavailability study (part 1), patients 18 years or older with advanced solid tumors were randomized to receive TAS-102 tablets (60 mg; 3 × 20-mg tablets) on day 1 and TAS-102 oral solution (60 mg) on days 8 and 15, or the opposite sequence. In an extension (part 2), all patients received TAS-102 tablets. Of the 46 patients treated in the crossover study, 38 were evaluable in the crossover bioavailability pharmacokinetic population. For area under the concentration-time curve (AUC)0-∞ and AUC0-last for FTD and TPI, and maximum plasma concentration (Cmax ) for TPI, the 90% confidence intervals (CIs) of the geometric mean ratios were within the 0.80 to 1.25 boundary for demonstration of bioequivalence; for FTD Cmax , the lower limit of the 90%CI was 0.786. The most frequently reported treatment-related grade 3 or 4 adverse events were neutropenia (7 patients) and decreased neutrophil count (3 patients). Although the lower limit of the 90%CI for the geometric mean ratio of FTD Cmax was slightly lower than 0.80, the bioavailability of the TAS-102 tablet is considered clinically similar to that of a TAS-102 oral solution. TAS-102 was well tolerated in this population of patients with advanced solid tumors. © 2016, The American College of Clinical Pharmacology.

  12. Multicenter, open-label, randomized phase II controlled trial of an investigational recombinant Meningococcal serogroup B vaccine with and without outer membrane vesicles, administered in infancy.

    Science.gov (United States)

    Findlow, Jamie; Borrow, Ray; Snape, Matthew D; Dawson, Tom; Holland, Ann; John, Tessa M; Evans, Anita; Telford, Karen L; Ypma, Ellen; Toneatto, Daniela; Oster, Philipp; Miller, Elizabeth; Pollard, Andrew J

    2010-11-15

    In the absence of an efficacious broadly protective vaccine, serogroup B Neisseria meningitidis (MenB) is the leading cause of bacterial meningitis and septicemia in many industrialized countries. An investigational recombinant vaccine that contains 3 central proteins; Neisserial adhesin A (NadA), factor H binding protein (fHBP) and Neisserial heparin binding antigen (NHBA) has been developed. These antigens have been formulated with and without outer membrane vesicles (rMenB+OMV and rMenB, respectively) from the New Zealand epidemic strain (B:4:P1.7-2,4). In this trial, we assessed the immunogenicity of these formulations in infants, who are at greatest risk of contracting MenB disease. A total of 147 infants from the United Kingdom were enrolled and randomly assigned to receive rMenB or rMenB+OMV at 2, 4, 6, and 12 months of age or a single dose at 12 months of age. Serum samples taken before and after vaccination were assayed in a standardized serum bactericidal antibody assay against 7 MenB strains. Local and systemic reactogenicity were recorded for 7 days after each vaccination. Analysis was according to protocol. After 3 doses, both vaccines were immunogenic against strains expressing homologous or related NadA and fHBP. rMenB+OMV demonstrated greater immunogenicity than did rMenB and was immunogenic against strains expressing homologous PorA. Both vaccines elicited anamnestic responses after the fourth dose. For both vaccines, responses were lower against strains expressing heterologous fHBP variants and after a single dose at 12 months. The rMenB+OMV vaccine has the potential to protect infants from MenB disease, although the breadth of protection afforded to heterologous antigens requires additional investigation.

  13. Efficacy and safety of degarelix in Korean patients with prostate cancer requiring androgen deprivation therapy: Open-label multicenter phase III study

    Directory of Open Access Journals (Sweden)

    Dalsan You

    2015-03-01

    Conclusions: Overall, degarelix was effective and well tolerated in Korean patients. Testosterone suppression was noninferior to that in non-Asian patients and safety findings were as would be expected for elderly men with PCa undergoing androgen deprivation therapy.

  14. TAS-102 plus bevacizumab for patients with metastatic colorectal cancer refractory to standard therapies (C-TASK FORCE): an investigator-initiated, open-label, single-arm, multicentre, phase 1/2 study.

    Science.gov (United States)

    Kuboki, Yasutoshi; Nishina, Tomohiro; Shinozaki, Eiji; Yamazaki, Kentaro; Shitara, Kohei; Okamoto, Wataru; Kajiwara, Takeshi; Matsumoto, Toshihiko; Tsushima, Takahiro; Mochizuki, Nobuo; Nomura, Shogo; Doi, Toshihiko; Sato, Akihiro; Ohtsu, Atsushi; Yoshino, Takayuki

    2017-09-01

    In patients with heavily treated metastatic colorectal cancer, TAS-102-a combination of trifluridine and tipiracil-has shown a significant overall survival benefit compared with placebo. In preclinical models, TAS-102 plus bevacizumab has shown enhanced activity against colorectal cancer xenografts compared with that for either drug alone. In this phase 1/2 study, we assessed the activity and safety of TAS-102 plus bevacizumab. We did this investigator-initiated, open-label, single-arm, multicentre, phase 1/2 trial of TAS-102 plus bevacizumab in four cancer centres in Japan. Eligible patients were aged 20 years or older; had histologically confirmed unresectable, metastatic colorectal adenocarcinoma; were refractory or intolerant to fluoropyrimidine, irinotecan, oxaliplatin, anti-VEGF therapy, and anti-EGFR therapy (for tumours with wild-type KRAS); and had no previous treatment with regorafenib. Patients had to have an Eastern Cooperative Oncology Group performance status of 0 or 1. Using a dose de-escalation design in phase 1, the recommended phase 2 dose (RP2D) was determined for TAS-102 (35 mg/m(2) given orally twice daily on days 1-5 and 8-12 in a 28-day cycle for level 1) plus bevacizumab (5 mg/kg, administered by intravenous infusion for 30 min every 2 weeks). In phase 2, patients received the RP2D. The primary endpoint was centrally assessed progression-free survival at 16 weeks, analysed in the first 21 patients to be enrolled and treated with the RP2D who had at least one imaging assessment. This study is completed and registered with the University Hospital Medical Information Network, number UMIN000012883. Between Feb 25, 2014, and July 23, 2014, we enrolled 25 patients with metastatic colorectal cancer: six patients in phase 1 and 19 patients in phase 2. The six patients who received TAS-102 at level 1 experienced no dose-limiting toxicities and this was deemed the RP2D. Nine of 21 patients who received the RP2D did not have a centrally assessed

  15. Bronchodilator efficacy of 18 µg once-daily tiotropium inhalation via Discair® versus HandiHaler® in adults with chronic obstructive pulmonary disease: randomized, active-controlled, parallel-group, open-label, Phase IV trial

    Directory of Open Access Journals (Sweden)

    Yildiz P

    2016-11-01

    Full Text Available Pinar Yildiz, Mesut Bayraktaroglu, Didem Gorgun, Funda Secik Clinics of Chest Diseases, Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Istanbul, Turkey Purpose: To compare the bronchodilator efficacy of 18 µg once-daily tiotropium inhalation administered via Discair® versus HandiHaler® in adults with moderate-to-severe chronic obstructive pulmonary disease (COPD.Patients and methods: Fifty-eight patients with moderate-to-severe COPD were enrolled in this randomized, active-controlled, parallel-group, open-label, Phase IV non-inferiority trial. Patients were randomly assigned to a test group (n=29, inhalation with Discair or a reference group (n=29, inhalation with HandiHaler. The primary efficacy parameter was the average maximum change in forced expiratory volume in 1 second (FEV1, in L. Change in forced vital capacity (FVC, in L, %FEV1 and %FVC, the standardized area under the response–time curve (AUC for the absolute change in FEV1 and FVC, time to onset and peak of response, and safety data were also evaluated.Results: The test inhaler was non-inferior to the reference inhaler in terms of maximum change in FEV1 at 24 h (unadjusted change: 0.0017 L [95% confidence interval [CI]: –0.0777, 0.0812]; change adjusted for time to reach maximum change in FEV1 and smoking in pack-years: 0.0116 L [95% CI: –0.0699, 0.0931], based on a non-inferiority margin of 0.100 L. There were also no significant differences between the two groups in maximum change in FVC value from baseline (0.3417 L vs 0.4438 L, P=0.113, percent change from baseline (22.235 vs 20.783 for FEV1, P=0.662; 16.719 vs 20.337 for FVC, P=0.257, and AUC0–24 h (2.949 vs 2.833 L for FEV1, P=0.891; 2.897 vs 4.729 L for FVC, P=0.178. There were no adverse events, serious adverse events, or deaths.Conclusion: Our findings show that the Discair was non-inferior to the HandiHaler. More specifically, these devices had similar clinical efficacy in terms of

  16. Raltegravir for the treatment of patients co-infected with HIV and tuberculosis (ANRS 12 180 Reflate TB): a multicentre, phase 2, non-comparative, open-label, randomised trial.

    Science.gov (United States)

    Grinsztejn, Beatriz; De Castro, Nathalie; Arnold, Vincent; Veloso, Valdiléa G; Morgado, Mariza; Pilotto, José Henrique; Brites, Carlos; Madruga, José Valdez; Barcellos, Nêmora Tregnago; Santos, Breno Riegel; Vorsatz, Carla; Fagard, Catherine; Santini-Oliveira, Marilia; Patey, Olivier; Delaugerre, Constance; Chêne, Geneviève; Molina, Jean-Michel

    2014-06-01

    Concurrent treatment of HIV and tuberculosis is complicated by drug interactions. We explored the safety and efficacy of raltegravir as an alternative to efavirenz for patients co-infected with HIV and tuberculosis. We did a multicentre, phase 2, non-comparative, open-label, randomised trial at eight sites in Brazil and France. Using a computer-generated randomisation sequence, we randomly allocated antiretroviral-naive adult patients with HIV-1 and tuberculosis (aged ≥18 years with a plasma HIV RNA concentration of >1000 copies per mL) to receive raltegravir 400 mg twice a day, raltegravir 800 mg twice daily, or efavirenz 600 mg once daily plus tenofovir and lamivudine (1:1:1; stratified by country). Patients began study treatment after the start of tuberculosis treatment. The primary endpoint was virological suppression at 24 weeks (HIV RNA <50 copies per mL) in all patients who received at least one dose of study drug (modified intention-to-treat analysis). We recorded death, study drug discontinuation, and loss to follow-up as failures to achieve the primary endpoint. We assessed safety in all patients who received study drugs. This study is registered in ClinicalTrials.gov, number NCT00822315. Between July 3, 2009, and June 6, 2011, we enrolled and randomly assigned treatment to 155 individuals; 153 (51 in each group) received at least one dose of the study drug and were included in the primary analysis. 133 patients (87%) completed follow-up at week 48. At week 24, virological suppression was achieved in 39 patients (76%, 95% CI 65-88) in the raltegravir 400 mg group, 40 patients (78%, 67-90) in the raltegravir 800 mg group, and 32 patients (63%, 49-76) in the efavirenz group. The adverse-event profile was much the same across the three groups. Three (6%) patients allocated to efavirenz and three (6%) patients allocated to raltegravir 800 mg twice daily discontinued the study drugs due to adverse events. Seven patients died during the study (one in the

  17. A Phase 1, randomized, open-label crossover study to evaluate the safety and pharmacokinetics of 400 mg albaconazole administered to healthy participants as a tablet formulation versus a capsule formulation

    Directory of Open Access Journals (Sweden)

    van Rossem K

    2013-01-01

    Full Text Available Koen van Rossem,1 Jenny A Lowe21Stiefel, Research Triangle Park, NC, USA; 2Stiefel, Stockley Park West, Uxbridge, UKBackground: Albaconazole is a novel triazole being developed for the oral treatment of fungal diseases. Once-weekly oral dosing with 400 mg albaconazole for 24 or 36 weeks resulted in high rates of clinical and mycological resolution for distal subungual onychomycosis, as well as a favorable safety and tolerability profile.Purpose: To compare four 100-mg albaconazole capsules to one 400-mg albaconazole tablet for bioavailability, bioequivalence, tolerability, and safety.Patients and methods: Forty participants were enrolled in this Phase I, open-label, two-sequence crossover study. Twenty participants were exposed to a single 400-mg tablet dose of albaconazole before being crossed over to a single dose of four 100-mg albaconazole capsules. The second group of 20 participants received the study products in reverse order. Blood samples were taken over 15 days post-dose to assess the plasma concentrations and pharmacokinetic parameters of albaconazole and its primary metabolite, 6-hydroxyalbaconazole. Safety was assessed throughout the study.Results: The area under the curve (AUC and maximum measured plasma concentration (Cmax of the albaconazole tablet were approximately 10% and 22% lower, respectively, than for the albaconazole capsules. Statistical significance was reached for the Cmax but not for the AUC measurements (AUC0-t and AUC0-inf. Because the 90% confidence intervals based on the differences between the tablet and capsule were outside the 80%–125% range for both the Cmax and AUC, we concluded that the formulations were not bioequivalent with respect to the rate or extent of absorption. Both formulations were safe and well-tolerated in this study. All adverse events (AEs were generally mild and were mainly gastrointestinal- or nervous system-related (eg, dizziness, headache. No electrocardiogram findings were reported as

  18. Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase 1/2 open-label, dose escalation study

    Science.gov (United States)

    O'Sullivan, Amy; Kennedy, Ryan C.; Abbas, Mohammad; Dai, Lijun; Pregja, Silvana Lalo; Burt, Steve; Boyiadzis, Michael; Roodman, G. David; Mapara, Markus Y.; Agha, Mounzer; Waas, John; Shuai, Yongli; Normolle, Daniel; Zonder, Jeffrey A.

    2012-01-01

    This multicenter phase 1/2 trial investigated the combination of bendamustine, lenalidomide, and dexamethasone in repeating 4-week cycles as treatment for relapsed refractory multiple myeloma (MM). Phase 1 established maximum tolerated dose (MTD). Phase 2 assessed overall response rate at the MTD. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). A total of 29 evaluable patients were enrolled. Median age was 63 years (range, 38-80 years). Median number of prior therapies was 3 (range, 1-6). MTD was bendamustine 75 mg/m2 (days 1 and 2), lenalidomide 10 mg (days 1-21), and dexamethasone 40 mg (weekly) of a 28-day cycle. Partial response rate was 52%, with very good partial response achieved in 24%, and minimal response in an additional 24% of patients. Median follow-up was 13 months; median OS has not been reached. One-year OS is 93% (95% confidence interval [CI], 59%-99%). Median PFS is 6.1 months (95% CI, 3.7-9.4 months) with one-year PFS of 20% (95% CI, 6%-41%). Grade 3/4 adverse events included neutropenia, thrombocytopenia, anemia, hyperglycemia, and fatigue. This first phase 1/2 trial testing bendamustine, lenalidomide, and dexamethasone as treatment of relapsed refractory MM was feasible and highly active. This study is registered at www.clinicaltrials.gov as #NCT01042704. PMID:22451423

  19. Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80 years or older: an open-label, multicentre, single-arm, phase 2 trial from the LYSA group.

    Science.gov (United States)

    Peyrade, Frédéric; Bologna, Serge; Delwail, Vincent; Emile, Jean François; Pascal, Laurent; Fermé, Christophe; Schiano, Jean-Marc; Coiffier, Bertrand; Corront, Bernadette; Farhat, Hassan; Fruchart, Christophe; Ghesquieres, Herve; Macro, Margaret; Tilly, Hervé; Choufi, Bachra; Delarue, Richard; Fitoussi, Olivier; Gabarre, Jean; Haioun, Corinne; Jardin, Fabrice

    2017-01-01

    In 2011 we reported a rituximab plus miniCHOP (reduced-dose cyclophosphamide, doxorubicin, vincristine, and prednisone) combination for patients older than 80 years with diffuse large B-cell lymphoma (DLBCL). The 2-year overall survival was 59% (95% CI 49-67) with an excess of early toxicity. To improve those results we tested the same chemotherapy protocol in combination with ofatumumab and a pre-phase treatment. For this open-label, multicentre, single-group, phase 2 trial, we recruited patients older than 80 years with untreated histologically-proven CD20-positive DLBCL, Ann Arbor stage I to IV, from 41 academic and hospital centres in France and Belgium. Patients received a pre-phase with oral vincristine (1 mg total dose 1 week before cycle 1 [day -7]) and oral prednisone (60 mg total dose starting 1 week before cycle 1, for 4 days [day -7 to day -4]) before the first cycle of the ofatumumab plus miniCHOP regimen. The regimen consisted of 1000 mg total dose of intravenous ofatumumab, 25 mg/m(2) of intravenous doxorubicin, 400 mg/m(2) of intravenous cyclophosphamide, and 1 mg of intravenous vincristine, on day 1 of each cycle; and 40 mg/m(2) of oral prednisone on days 1-5. Ofatumumab was administered with 1000 mg of paracetamol and 50 mg of diphenhydramine. The primary endpoint was overall survival in the intention-to-treat population. The statistical analysis has been done on an intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT01195714. Between June 2, 2010, and Nov 4, 2011, we enrolled 120 patients. Age-adjusted International Prognostic Index was 2-3 in 68 (57%) of them. The median follow-up time was 26·8 months (IQR 24·5-30·1). The 2-year overall survival was 64·7% (95% CI 55·3-72·7) and median overall survival was not reached (95% CI 30·2-not reached). 45 patients died during the treatment, of whom 28 (62%) died due to lymphoma. The most common side-effect was haematological toxicity. Among the 120 patients

  20. Maintenance capecitabine and bevacizumab versus bevacizumab alone after initial first-line bevacizumab and docetaxel for patients with HER2-negative metastatic breast cancer (IMELDA): a randomised, open-label, phase 3 trial.

    Science.gov (United States)

    Gligorov, Joseph; Doval, Dinesh; Bines, José; Alba, Emilio; Cortes, Paulo; Pierga, Jean-Yves; Gupta, Vineet; Costa, Rômulo; Srock, Stefanie; de Ducla, Sabine; Freudensprung, Ulrich; Mustacchi, Giorgio

    2014-11-01

    Longer duration of first-line chemotherapy for patients with metastatic breast cancer is associated with prolonged overall survival and improved progression-free survival. We investigated capecitabine added to maintenance bevacizumab after initial treatment with bevacizumab and docetaxel in this setting. We did this open-label randomised phase 3 trial at 54 hospitals in Brazil, China, Egypt, France, Hong Kong, India, Italy, Poland, Spain, and Turkey. We enrolled patients with HER2-negative measurable metastatic breast cancer; each received three to six cycles of first-line bevacizumab (15 mg/kg) and docetaxel (75-100 mg/m(2)) every 3 weeks. Progression-free patients were randomly assigned with an interactive voice-response system by block (size four) randomisation (1:1) to receive either bevacizumab and capecitabine or bevacizumab only (bevacizumab 15 mg/kg on day 1; capecitabine 1000 mg/m(2) twice per day on days 1-14, every 3 weeks) until progression, stratified by oestrogen receptor status (positive vs negative), visceral metastases (present vs absent), response status (stable disease vs response vs non-measurable), and lactate dehydrogenase concentration (≤1·5 vs >1·5 × upper limit of normal). Neither patients nor investigators were masked to allocation. The primary endpoint was progression-free survival (from randomisation) in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT00929240. Between July 16, 2009, and March 7, 2011 (when enrolment was prematurely terminated), 284 patients received initial bevacizumab and docetaxel; 185 (65%) were randomly assigned (91 to bevacizumab and capecitabine versus 94 to bevacizumab only). Progression-free survival was significantly longer in the bevacizumab and capecitabine group than in the bevacizumab only group (median 11·9 months [95% CI 9·8-15·4] vs 4·3 months [3·9-6·8]; stratified hazard ratio 0·38 [95% CI 0·27-0·55]; two-sided log-rank p<0·0001), as was overall

  1. Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): an open-label, phase 3, randomised controlled trial.

    Science.gov (United States)

    Azzouzi, Abdel-Rahmène; Vincendeau, Sébastien; Barret, Eric; Cicco, Antony; Kleinclauss, François; van der Poel, Henk G; Stief, Christian G; Rassweiler, Jens; Salomon, Georg; Solsona, Eduardo; Alcaraz, Antonio; Tammela, Teuvo T; Rosario, Derek J; Gomez-Veiga, Francisco; Ahlgren, Göran; Benzaghou, Fawzi; Gaillac, Bertrand; Amzal, Billy; Debruyne, Frans M J; Fromont, Gaëlle; Gratzke, Christian; Emberton, Mark

    2017-02-01

    Vascular-targeted photodynamic therapy, a novel tissue-preserving treatment for low-risk prostate cancer, has shown favourable safety and efficacy results in single-arm phase 1 and 2 studies. We compared this treatment with the standard of care, active surveillance, in men with low-risk prostate cancer in a phase 3 trial. This randomised controlled trial was done in 47 European university centres and community hospitals. Men with low-risk, localised prostate cancer (Gleason pattern 3) who had received no previous treatment were randomly assigned (1:1) to vascular-targeted photodynamic therapy (4 mg/kg padeliporfin intravenously over 10 min and optical fibres inserted into the prostate to cover the desired treatment zone and subsequent activation by laser light 753 nm with a fixed power of 150 mW/cm for 22 min 15 s) or active surveillance. Randomisation was done by a web-based allocation system stratified by centre with balanced blocks of two or four patients. Best practice for active surveillance at the time of study design was followed (ie, biopsy at 12-month intervals and prostate-specific antigen measurement and digital rectal examination at 3-month intervals). The co-primary endpoints were treatment failure (histological progression of cancer from low to moderate or high risk or death during 24 months' follow-up) and absence of definite cancer (absence of any histology result definitely positive for cancer at month 24). Analysis was by intention to treat. Treatment was open-label, but investigators assessing primary efficacy outcomes were masked to treatment allocation. This trial is registered with ClinicalTrials.gov, number NCT01310894. Between March 8, 2011, and April 30, 2013, we randomly assigned 206 patients to vascular-targeted photodynamic therapy and 207 patients to active surveillance. Median follow-up was 24 months (IQR 24-25). The proportion of participants who had disease progression at month 24 was 58 (28%) of 206 in the vascular

  2. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open-label, non-inferiority, randomised trial.

    Science.gov (United States)

    Goldstein, Joshua N; Refaai, Majed A; Milling, Truman J; Lewis, Brandon; Goldberg-Alberts, Robert; Hug, Bruce A; Sarode, Ravi

    2015-05-23

    Rapid reversal of vitamin K antagonist (VKA)-induced anticoagulation is often necessary for patients needing urgent surgical or invasive procedures. The optimum means of VKA reversal has not been established in comparative clinical trials. We compared the efficacy and safety of four-factor prothrombin complex concentrate (4F-PCC) with that of plasma in VKA-treated patients needing urgent surgical or invasive procedures. In a multicentre, open-label, phase 3b randomised trial we enrolled patients aged 18 years or older needing rapid VKA reversal before an urgent surgical or invasive procedure. We randomly assigned patients in a 1:1 ratio to receive vitamin K concomitant with a single dose of either 4F-PCC (Beriplex/Kcentra/Confidex; CSL Behring, Marburg, Germany) or plasma, with dosing based on international normalised ratio (INR) and weight. The primary endpoint was effective haemostasis, and the co-primary endpoint was rapid INR reduction (≤1·3 at 0·5 h after infusion end). The analyses were intended to evaluate, in a hierarchical fashion, first non-inferiority (lower limit 95% CI greater than -10% for group difference) for both endpoints, then superiority (lower limit 95% CI >0%) if non-inferiority was achieved. Adverse events and serious adverse events were reported to days 10 and 45, respectively. This trial is registered at ClinicalTrials.gov, number NCT00803101. 181 patients were randomised (4F-PCC n=90; plasma n=91). The intention-to-treat efficacy population comprised 168 patients (4F-PCC, n=87; plasma, n=81). Effective haemostasis was achieved in 78 (90%) patients in the 4F-PCC group compared with 61 (75%) patients in the plasma group, demonstrating both non-inferiority and superiority of 4F-PCC over plasma (difference 14·3%, 95% CI 2·8-25·8). Rapid INR reduction was achieved in 48 (55%) patients in the 4F-PCC group compared with eight (10%) patients in the plasma group, demonstrating both non-inferiority and superiority of 4F-PCC over plasma

  3. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial.

    Science.gov (United States)

    Thatcher, Nick; Hirsch, Fred R; Luft, Alexander V; Szczesna, Aleksandra; Ciuleanu, Tudor E; Dediu, Mircea; Ramlau, Rodryg; Galiulin, Rinat K; Bálint, Beatrix; Losonczy, György; Kazarnowicz, Andrzej; Park, Keunchil; Schumann, Christian; Reck, Martin; Depenbrock, Henrik; Nanda, Shivani; Kruljac-Letunic, Anamarija; Kurek, Raffael; Paz-Ares, Luis; Socinski, Mark A

    2015-07-01

    Necitumumab is a second-generation, recombinant, human immunoglobulin G1 EGFR antibody. In this study, we aimed to compare treatment with necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone in patients with previously untreated stage IV squamous non-small-cell lung cancer. We did this open-label, randomised phase 3 study at 184 investigative sites in 26 countries. Patients aged 18 years or older with histologically or cytologically confirmed stage IV squamous non-small-cell lung cancer, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and adequate organ function and who had not received previous chemotherapy for their disease were eligible for inclusion. Enrolled patients were randomly assigned centrally 1:1 to a maximum of six 3-week cycles of gemcitabine and cisplastin chemotherapy with or without necitumumab according to a block randomisation scheme (block size of four) by a telephone-based interactive voice response system or interactive web response system. Chemotherapy was gemcitabine 1250 mg/m(2) administered intravenously over 30 min on days 1 and 8 of a 3-week cycle and cisplatin 75 mg/m(2) administered intravenously over 120 min on day 1 of a 3-week cycle. Necitumumab 800 mg, administered intravenously over a minimum of 50 min on days 1 and 8, was continued after the end of chemotherapy until disease progression or intolerable toxic side-effects occurred. Randomisation was stratified by ECOG performance status and geographical region. Neither physicians nor patients were masked to group assignment because of the expected occurrence of acne-like rash--a class effect of EGFR antibodies--that would have unmasked most patients and investigators to treatment. The primary endpoint was overall survival, analysed by intention to treat. We report the final clinical analysis. This study is registered with ClinicalTrials.gov, number NCT00981058. Between Jan 7, 2010, and Feb 22, 2012, we enrolled 1093 patients

  4. Neridronate improves bone mineral density and reduces back pain in β-thalassaemia patients with osteoporosis: results from a phase 2, randomized, parallel-arm, open-label study.

    Science.gov (United States)

    Forni, Gian Luca; Perrotta, Silverio; Giusti, Andrea; Quarta, Giovanni; Pitrolo, Lorella; Cappellini, Maria Domenica; D'Ascola, Domenico Giuseppe; Borgna Pignatti, Caterina; Rigano, Paolo; Filosa, Aldo; Iolascon, Giovanni; Nobili, Bruno; Baldini, Marina; Rosa, Alessandra; Pinto, Valeria; Palummeri, Ernesto

    2012-07-01

    Neridronate is a third generation bisphosphonate with established efficacy in metabolic bone disease. In this randomized, open-label study, 118 adults with β-thalassaemia and bone mineral density (BMD) Z scores ≤-2·0 were randomized 1:1-500 mg calcium with 400 international unis (iu) vitamin D daily or 500 mg calcium with 400 iu vitamin D daily plus neridronate 100 mg intravenously every 90 d. Significant increases in BMD at the lumbar spine and total hip were noted in the neridronate group at 6 and 12 months from baseline (P back pain and analgesic use were also evident, starting 3 months from commencing treatment. Treatment was well tolerated by all patients. In this largest randomized trial in thalassaemia-induced osteoporosis to date, neridronate was safe and effective in reducing bone resorption and increasing BMD. The associated reduction in back pain and improved quality of life will encourage adherence to therapy. (Clinicaltrials.gov identifier NCT01140321.).

  5. Maintenance strategies after first-line oxaliplatin plus fluoropyrimidine plus bevacizumab for patients with metastatic colorectal cancer (AIO 0207): a randomised, non-inferiority, open-label, phase 3 trial.

    Science.gov (United States)

    Hegewisch-Becker, Susanna; Graeven, Ullrich; Lerchenmüller, Christian A; Killing, Birgitta; Depenbusch, Reinhard; Steffens, Claus-Christoph; Al-Batran, Salah-Eddin; Lange, Thoralf; Dietrich, Georg; Stoehlmacher, Jan; Tannapfel, Andrea; Reinacher-Schick, Anke; Quidde, Julia; Trarbach, Tanja; Hinke, Axel; Schmoll, Hans-Joachim; Arnold, Dirk

    2015-10-01

    The definition of a best maintenance strategy following combination chemotherapy plus bevacizumab in metastatic colorectal cancer is unclear. We investigated whether no continuation of therapy or bevacizumab alone are non-inferior to fluoropyrimidine plus bevacizumab, following induction treatment with a fluoropyrimidine plus oxaliplatin plus bevacizumab. In this open-label, non-inferiority, randomised phase 3 trial, we included patients aged 18 years or older with histologically confirmed, previously untreated metastatic colorectal cancer, Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, adequate bone marrow, liver, and renal function, no pre-existing neuropathy greater than grade 1, and measurable disease, from 55 hospitals and 51 private practices in Germany. After 24 weeks of induction therapy with either fluorouracil plus leucovorin plus oxaliplatin or capecitabine plus oxaliplatin, both with bevacizumab, patients without disease progression were randomly assigned centrally by fax (1:1:1) to standard maintenance treatment with a fluoropyrimidine plus bevacizumab, bevacizumab alone, or no treatment. Both patients and investigators were aware of treatment assignment. Stratification criteria were response status, termination of oxaliplatin, previous adjuvant treatment with oxaliplatin, and ECOG performance status. At first progression, re-induction with all drugs of the induction treatment was a planned part of the protocol. Time to failure of strategy was the primary endpoint, defined as time from randomisation to second progression after maintenance (and if applicable re-induction), death, or initiation of further treatment including a new drug. Time to failure of strategy was equivalent to time to first progression for patients who did not receive re-induction (for any reason). The boundary for assessment of non-inferiority was upper limit of the one-sided 98·8% CI 1·43. Analyses were done by intention to treat. The study has completed

  6. Icotinib versus whole-brain irradiation in patients with EGFR-mutant non-small-cell lung cancer and multiple brain metastases (BRAIN): a multicentre, phase 3, open-label, parallel, randomised controlled trial.

    Science.gov (United States)

    Yang, Jin-Ji; Zhou, Caicun; Huang, Yisheng; Feng, Jifeng; Lu, Sun; Song, Yong; Huang, Cheng; Wu, Gang; Zhang, Li; Cheng, Ying; Hu, Chengping; Chen, Gongyan; Zhang, Li; Liu, Xiaoqing; Yan, Hong Hong; Tan, Fen Lai; Zhong, Wenzhao; Wu, Yi-Long

    2017-09-01

    For patients with non-small-cell lung cancer (NSCLC) and multiple brain metastases, whole-brain irradiation (WBI) is a standard-of-care treatment, but its effects on neurocognition are complex and concerning. We compared the efficacy of an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), icotinib, versus WBI with or without chemotherapy in a phase 3 trial of patients with EGFR-mutant NSCLC and multiple brain metastases. We did a multicentre, open-label, parallel randomised controlled trial (BRAIN) at 17 hospitals in China. Eligible participants were patients with NSCLC with EGFR mutations, who were naive to treatment with EGFR-TKIs or radiotherapy, and had at least three metastatic brain lesions. We randomly assigned participants (1:1) to either icotinib 125 mg orally (three times per day) or WBI (30 Gy in ten fractions of 3 Gy) plus concurrent or sequential chemotherapy for 4-6 cycles, until unacceptable adverse events or intracranial disease progression occurred. The randomisation was done by the Chinese Thoracic Oncology Group with a web-based allocation system applying the Pocock and Simon minimisation method; groups were stratified by EGFR gene mutation status, treatment line (first line or second line), brain metastases only versus both intracranial and extracranial metastases, and presence or absence of symptoms of intracranial hypertension. Clinicians and patients were not masked to treatment assignment, but individuals involved in the data analysis did not participate in the treatments and were thus masked to allocation. Patients receiving icotinib who had intracranial progression only were switched to WBI plus either icotinib or chemotherapy until further progression; those receiving icotinib who had extracranial progression only were switched to icotinib plus chemotherapy. Patients receiving WBI who progressed were switched to icotinib until further progression. Icotinib could be continued beyond progression if a clinical benefit

  7. Safety and activity of microRNA-loaded minicells in patients with recurrent malignant pleural mesothelioma: a first-in-man, phase 1, open-label, dose-escalation study.

    Science.gov (United States)

    van Zandwijk, Nico; Pavlakis, Nick; Kao, Steven C; Linton, Anthony; Boyer, Michael J; Clarke, Stephen; Huynh, Yennie; Chrzanowska, Agata; Fulham, Michael J; Bailey, Dale L; Cooper, Wendy A; Kritharides, Leonard; Ridley, Lloyd; Pattison, Scott T; MacDiarmid, Jennifer; Brahmbhatt, Himanshu; Reid, Glen

    2017-10-01

    TargomiRs are minicells (EnGeneIC Dream Vectors) loaded with miR-16-based mimic microRNA (miRNA) and targeted to EGFR that are designed to counteract the loss of the miR-15 and miR-16 family miRNAs, which is associated with unsuppressed tumour growth in preclinical models of malignant pleural mesothelioma. We aimed to assess the safety, optimal dosing, and activity of TargomiRs in patients with malignant pleural mesothelioma. In this first-in-man, open-label, dose-escalation phase 1 trial at three major cancer centres in Sydney (NSW, Australia), we recruited adults (aged ≥18 years) with a confirmed diagnosis of malignant pleural mesothelioma, measurable disease, radiological signs of progression after previous chemotherapy, Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of 3 months or more, immunohistochemical evidence of tumour EGFR expression, and adequate bone marrow, liver, and renal function. Patients were given TargomiRs via 20 min intravenous infusion either once or twice a week (3 days apart) in a traditional 3 + 3 dose-escalation design in five dose cohorts. The dose-escalation steps planned were 5 × 10(9), 7 × 10(9), and 9 × 10(9) TargomiRs either once or twice weekly, but after analysis of data from the first eight patients, all subsequent patients started protocol treatment at 1 × 10(9) TargomiRs. The primary endpoints were to establish the maximum tolerated dose of TargomiRs as measured by dose-limiting toxicity, define the optimal frequency of administration, and objective response (defined as the percentage of assessable patients with a complete or partial response), duration of response (defined as time from the first evidence of response to disease progression in patients who achieved a response), time to response (ie, time from start of treatment to the first evidence of response) and overall survival (defined as time from treatment allocation to death from any cause). Analyses were based

  8. A multicenter, primary-care-based, open-label study to assess the success of converting opioid-experienced patients with chronic moderate-to-severe pain to morphine sulfate and naltrexone hydrochloride extended-release capsules using a standardized conversion guide

    Directory of Open Access Journals (Sweden)

    Setnik B

    2015-07-01

    Full Text Available Beatrice Setnik,1 Carl L Roland,1 Kenneth W Sommerville,1,2 Glenn C Pixton,1 Robert Berke,3,4 Anne Calkins,5 Veeraindar Goli1,2 1Pfizer Inc, 2Duke University Medical Center, Durham, NC, USA; 3Family Health Medical Services PLLC, Mayville, 4Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, 5New York Spine & Wellness Center, Syracuse, NY, USA Objective: To evaluate the conversion of opioid-experienced patients with chronic moderate-to-severe pain to extended-release morphine sulfate with sequestered naltrexone hydrochloride (MSN using a standardized conversion guide. Methods: This open-label, single-arm study was conducted in 157 primary care centers in the United States. A total of 684 opioid-experienced adults with chronic moderate-to-severe pain were converted to oral administration of MSN from transdermal fentanyl and oral formulations of hydrocodone, hydromorphone, methadone, oxycodone, oxymorphone, and other morphine products using a standardized conversion guide. The primary endpoint was the percentage of patients achieving a stable MSN dose within a 6-week titration phase. Secondary endpoints included duration of time to stable dose, number of titration steps, safety and efficacy measures, and investigator assessment of conversion guide utility. Results: Of the 684 patients, 51.3% were converted to a stable dose of MSN (95% confidence interval: 47.5%, 55.1%. The mean (standard deviation number of days to stable dose was 20 (8.94, and number of titration steps to stable dose was 2.4 (1.37. The majority of adverse events were mild/moderate and consistent with opioid therapy. Mean pain scores at stable dose decreased from baseline. Investigators were generally satisfied with the conversion guide and, in 94% of cases, reported they would use it again. Conclusion: Conversion to MSN treatment using the standardized MSN conversion guide was an attainable goal in approximately half of the population of

  9. A 10-month, open-label evaluation of desvenlafaxine in Japanese outpatients with major depressive disorder.

    Science.gov (United States)

    Tourian, Karen; Wang, Ying; Ii, Yoichi

    2013-07-01

    The objective of this study was to evaluate the long-term safety of desvenlafaxine for continuation treatment of major depressive disorder (MDD) in Japanese patients. This was a phase 3, multicenter, 10-month, open-label study with flexible dosing of desvenlafaxine (25, 50, 100 mg/day). Japanese patients with MDD who had completed an 8-week, double-blind, placebo-controlled study in which patients received 25 or 50 mg/day desvenlafaxine or placebo were enrolled. In this study, patients received desvenlafaxine 25 mg/day from days 1 to 14, with subsequent upward titration, to a maximum of 100 mg/day, determined by clinical response. Of 304 patients, 75 (24.7%) discontinued during the on-therapy period; patient request was the most common reason (11.5%). Treatment-emergent adverse events were reported by 240 patients (78.9%) during the on-therapy period; the most common adverse events were nasopharyngitis (37.2%), somnolence (11.5%), headache (10.5%), and nausea (10.2%). For the ITT-LOCF population, the mean change from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D₁₇) total score was -4.76 (95% confidence interval: -5.47 to -4.05); continued numerical improvements in the HAM-D₁₇ total scores and other depression outcome measures were observed irrespective of treatment in the previous study. Long-term use of desvenlafaxine was safe and well tolerated, with a clinical benefit/risk profile similar to that in other populations.

  10. Necitumumab plus Gemcitabine and Cisplatin as First-Line Therapy in Patients with Stage IV EGFR- Expressing Squamous Non-Small-Cell Lung Cancer: German Subgroup Data from an Open-Label, Randomized Controlled Phase 3 Study (SQUIRE).

    Science.gov (United States)

    Reck, Martin; Thomas, Michael; Kropf-Sanchen, Cornelia; Mezger, Jörg; Socinski, Mark A; Depenbrock, Henrik; Soldatenkova, Victoria; Brown, Jacqueline; Krause, Thomas; Thatcher, Nick

    2016-01-01

    In the SQUIRE study, adding the anti-epidermal growth factor receptor (EGFR) IgG1 antibody necitumumab to first-line gemcitabine and cisplatin (GC + N) in advanced squamous non-small-cell lung cancer (sqNSCLC) significantly improved overall survival (OS); the safety profile was acceptable. We explored data for the German subpopulation (N = 96) of SQUIRE patients with EGFR-expressing tumors. Patients with stage IV sqNSCLC were randomized 1:1 to up to 6 cycles of open-label GC + N or GC alone. GC + N patients with no progression continued on necitumumab monotherapy until disease progression or intolerable toxicity. The primary endpoint was OS; the secondary endpoints included progression-free survival (PFS), safety and health-related quality of life (EQ-5D, Lung Cancer Symptom Scale (LCSS)). The 96 German SQUIRE patients with EGFR-expressing tumors (GC + N 42, GC 54) received a median of 4 GC cycles; the GC + N patients received 5 cycles of necitumumab. Adding necitumumab was associated with 41% risk reduction of death (hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.37-0.94, p = 0.026) and 44% risk reduction of progression (HR 0.56, 95% CI 0.33-0.95, p = 0.029). Adverse events typically associated with EGFR antibody treatment (including rash, hypomagnesemia) were more common with GC + N. The time to deterioration of the EQ-5D and LCSS scores showed no notable differences between the treatment arms, except for appetite loss (delayed for GC + N). The survival benefit from adding necitumumab to first-line GC was more pronounced in the German SQUIRE subpopulation with EGFR-expressing tumors than in the overall (intention-to-treat) population; toxicity was manageable and consistent with the overall population. © 2016 S. Karger GmbH, Freiburg.

  11. An open-label, phase 2, single centre, randomized, crossover design bioequivalence study of AndroForte 5 testosterone cream and Testogel 1% testosterone gel in hypogonadal men: study LP101.

    Science.gov (United States)

    Wittert, G A; Harrison, R W; Buckley, M J; Wlodarczyk, J

    2016-01-01

    We compared a novel 5% testosterone (T) cream (AndroForte 5, Lawley Pharmaceuticals, Australia) with a 1% T gel (Testogel, Besins Healthcare, Australia). Using an open-label crossover design, subjects were randomized to one of two treatment sequences using either the T gel or T cream first in a 1 : 1 ratio. Each treatment period was 30 days with a 7-14 days washout period between them. On Days 1 and 30 of each treatment period blood was sampled at -15, -5 min, 0, 2, 4, 5, 6, 7, 8, 9, 10, 12 and 16 h post study drug administration. Sixteen men with established androgen deficiency aged between 29 and 73 years, who had undertaken a washout from prior testosterone therapy participated in the study. One subject failed to complete both arms and another was excluded post-completion because of a major protocol violation. Bioequivalence was established based on key pharmacokinetic (PK) variables: AUC, C(avg), C(max), T(max), % fluctuation (with and without baseline correction) for the two formulations of testosterone on Day 1 and Day 30. The ratio and 90% CI of AUC 0.99 (0.86-1.14), C(max) 1.02 (0.84-1.24) and C(avg) 0.99 (0.86-1.14) for T cream/T gel were within the predetermined bio-equivalence criteria of 80% to 125% at Day 30. There were no statistically significant differences between secondary biochemical markers: serum dihydrotestosterone (DHT), oestradiol (E2), sex hormone-binding globulin (SHBG), luteinizing hormone (LH) and (FSH). The two testosterone formulations were shown to be bioequivalent.

  12. Efficacy and safety of ixekizumab treatment for Japanese patients with moderate to severe plaque psoriasis, erythrodermic psoriasis and generalized pustular psoriasis: Results from a 52-week, open-label, phase 3 study (UNCOVER-J).

    Science.gov (United States)

    Saeki, Hidehisa; Nakagawa, Hidemi; Nakajo, Ko; Ishii, Taeko; Morisaki, Yoji; Aoki, Takehiro; Cameron, Gregory S; Osuntokun, Olawale O

    2017-04-01

    Psoriasis, a chronic, immune-mediated skin disease characterized by red, scaly plaques, affects approximately 0.3% of the population in Japan. The aim of this open-label study was to evaluate the long-term efficacy and safety of ixekizumab, a humanized, anti-interleukin-17A monoclonal antibody, in Japanese patients with plaque psoriasis (n = 78, including 11 psoriatic arthritis), erythrodermic psoriasis (n = 8) and generalized pustular psoriasis (n = 5). Ixekizumab was administrated s.c. at baseline (week 0, 160 mg), from weeks 2 to 12 (80 mg every 2 weeks), and from weeks 16 to 52 (80 mg every 4 weeks). At week 52, 92.3% of patients with plaque psoriasis achieved Psoriasis Area and Severity Index (PASI) 75, 80.8% achieved PASI 90, 48.7% achieved PASI 100, and 52.6% had remission of plaques (by static Physician Global Assessment, sPGA [0]). Difficult to treat areas of psoriasis (nail or scalp) also responded to ixekizumab. All patients with psoriatic arthritis who were assessed (5/5) achieved an American College of Rheumatology 20 response. Most patients with erythrodermic psoriasis or generalized pustular psoriasis responded to ixekizumab and the clinical outcome was maintained over 52 weeks (75% and 60% of patients achieved sPGA [0, 1] at week 52, respectively). Mostly mild or moderate treatment-emergent adverse events were reported by 79 of 91 patients; the most common were nasopharyngitis, eczema, seborrheic dermatitis, urticaria and injection site reactions. In conclusion, 52-week ixekizumab treatment was efficacious and well tolerated in Japanese patients with plaque psoriasis. Efficacy was also observed in patients with erythrodermic psoriasis, generalized pustular psoriasis and psoriatic arthritis. © 2016 Eli Lilly Japan K.K. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.

  13. Monotherapy or add-on therapy with topiramate in elderly patients with epilepsy:results of an open-label multicenter triai%托吡酯多中心开放性治疗老年癫痫的临床观察

    Institute of Scientific and Technical Information of China (English)

    田季雨; 黄远桂; 胡安恒; 马磊; 尹庆春; 蔡艺灵

    2008-01-01

    Objective To assess the efficacy and adverse-event profile of monotherapy oradd-on therapy with topiramate in elderly patients with epilepsy. Methods A multicenter, prospective,open-label, observational study of topiramate, for either monotherapy or add-on therapy, was performedamong 119 elderly patients with epilepsy in the Outpatient Department of Neurology of 52 generalhospitals in China. After the baseline evaluation, topiramate was given at the target dose of 200 mg/dayover an 8-week titration period. In the subsequent 12-week maintenance period, the topiramate dose wasadjusted (200-300 mg) according to the clinical results. The patients were followed up for 6 months, withmonthly visits and regular physical, neurological and laboratory examinations. Results After themaintenance period, 106 patients (89.1%) showed a seizure frequency reduction by 50% or greater fromthe baseline, among whom 65 patients(93.8%)received the monotherapy and 54(83.8%) had the add-ontherapy. Topiramate monotherapy and add-on therapy resulted in a complete seizure control in over 50%of the patients with various types of seizure. In patients with disease course less than 1 year, between 1and 3 years, between 4 and 6 years, and over 6 years, topiramate monotherapy resulted in seizurereduction by 92.86%, 91.67%, 100%, and 94.44%, and the add-on therapy reduced the seizure by80.00%, 85.71%, 70.00%, and 86.36%, respectively. When combined with carbamazepine, valproatesodium, phenytoin, phenol barbital, and diazepam, the total effective rate oftopiramate was 79.41%,87.50%, 85.71%, 0%, and 80.00%, respectively. Topiramate, especially in monotherapy, caused onlymild or moderate adverse effects. Conclusion Topiramate is effective and safe for either monotherapyor add-on therapy of epilepsy in elderly patients. The types of epilepsy, disease course, or the drugs usedin the add-on therapy do no obviously affect the efficacy of topiramate for seizure control.%目的 研究单用或加用托吡酯

  14. Long-term tolerability of tolterodine extended release in children 5-11 years of age : Results from a 12-month, open-label study

    NARCIS (Netherlands)

    Nijman, Rien J. M.; Borgstein, Niels G.; Ellsworth, Pamela; Siggaard, Charlotte

    2007-01-01

    Objective: To evaluate the long-term tolerability of tolterodine extended release (ER) in children (aged 5-11 yr) with urgency urinary incontinence (UUI). Methods: This was a multicenter, open-label extension of a 12-wk, double-blind, placebo-controlled study of tolterodine ER. Patients had UUI sugg

  15. Efficacy and safety of a nano-emulsion gel formulation of adapalene 0.1% and clindamycin 1% combination in acne vulgaris: A randomized, open label, active-controlled, multicentric, phase IV clinical trial

    Directory of Open Access Journals (Sweden)

    Siva Prasad

    2012-01-01

    Full Text Available Background: Acne vulgaris is a very common skin disease with a significant detrimental effect on the quality of life of the patients. Aims: To assess the comparative efficacy and safety of a nano-emulsion gel formulation of adapalene and clindamycin combination with its conventional formulation in the treatment of acne vulgaris of the face. It was a prospective, randomized, open label, active-controlled, multicentric, clinical trial. Methods: Eligible patients suffering from acne vulgaris of the face were randomized to receive once-daily treatment with a nano-emulsion gel or conventional gel formulation of adapalene 0.1% and clindamycin (as phosphate 1% combination for 12 weeks. Total, inflammatory and noninflammatory lesion counts, with grading of acne severity were carried out on a monthly basis. Safety assessments were done to determine the comparative local and systemic tolerability. Two-tailed significance testing was carried out with appropriate statistical tests, and P-values < 0.05 were considered as significant. Results: 209/212 patients enrolled in the study were eligible for efficacy and safety assessments in both nano-emulsion gel (118/119 patients and conventional gel (91/93 patients groups. Significantly better reductions in total (79.7% vs. 62.7%, inflammatory (88.7% vs. 71.4% and noninflammatory (74.9% vs. 58.4% lesions were reported with the nano-emulsion gel as compared to the conventional gel (P < 0.001 for all. Mean acne severity score also reduced significantly more with the nano-emulsion formulation (1.9 ± 0.9 vs. 1.4 ± 1.0; P < 0.001 than the comparator. Significantly lower incidence and lesser intensity of adverse events like local irritation (4.2% vs. 19.8%; P < 0.05 and erythema (0.8% vs. 9.9%; P < 0.05 were recorded with the nano-emulsion gel. Conclusions: The nano-emulsion gel formulation of adapalene and clindamycin combination appears to be more efficacious and better tolerated than the conventional formulation

  16. Does Early Postsurgical Temozolomide Plus Concomitant Radiochemotherapy Regimen Have Any Benefit in Newly-diagnosed Glioblastoma Patients? A Multi-center,Randomized, Parallel, Open-label, Phase Ⅱ Clinical Trial

    Institute of Scientific and Technical Information of China (English)

    Ying Mao; Yu Yao; Li-Wei Zhang; Yi-Cheng Lu; Zhong-Ping Chen; Jian-Min Zhang; Song-Tao Qi

    2015-01-01

    Background:The radiochemotherapy regimen concomitantly employing temozolomide (TMZ) chemotherapy and radiotherapy (RT) 4 weeks after surgery,followed by 6 cycles of TMZ is a common treatment for glioblastoma (GBM).However,its median overall survival (OS) is only 14.6 months.This study was to explore the effectiveness and safety of early TMZ chemotherapy between surgery and chemoradiotherapy plus the standard concomitant radiochemotherapy regimen.Methods:A randomized,parallel group,open-label study of 99 newly diagnosed GBM patients was conducted at 1 0 independent Chinese neurosurgical departments from June 2008 to June 2012.Patients were treated with concomitant radiochemotherapy regimen plus early postsurgical temozolomide (early TMZ group) or standard concomitant radiochemotherapy regimen (control group).Overall response was assessed based on objective tumor assessments,administration ofcorticosteroid and neurological status test.Hematological,biochemical,laboratory,adverse event (AE),and neurological condition were measured for 24 months of follow-up.The primary efficacy endpoint of this study was overall survival (OS).The secondary endpoint was progression free survival (PFS).Results:The median OS time in the early TMZ group was 17.6 months,compared with 13.2 months in the control group (log-rank test P =0.021).In addition,the OS rate in the early TMZ group was higher at 6,12,and 18 months than in the control group,respectively (P <0.05).The median PFS time was 8.7 months in the early TMZ group and 10.4 months in the control group (log-rank test P =0.695).AEs occurred in 29 (55.8%) and 31(73.8%) patients respectively in early and control groups,including nausea (15.4% vs.33.3%),vomiting (7.7% vs.28.6%),fever (7.7% vs.11.9%),and headache (3.8% vs.23.8%).Only 30.8% and 33.3% were drug-related,respectively.Conclusions:Addition of TMZ chemotherapy in the early break of the standard concomitant radiochemotherapy regimen was well tolerated

  17. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial.

    Science.gov (United States)

    Récher, Christian; Coiffier, Bertrand; Haioun, Corinne; Molina, Thierry Jo; Fermé, Christophe; Casasnovas, Olivier; Thiéblemont, Catherine; Bosly, André; Laurent, Guy; Morschhauser, Franck; Ghesquières, Hervé; Jardin, Fabrice; Bologna, Serge; Fruchart, Christophe; Corront, Bernadette; Gabarre, Jean; Bonnet, Christophe; Janvier, Maud; Canioni, Danielle; Jais, Jean-Philippe; Salles, Gilles; Tilly, Hervé

    2011-11-26

    The outcome of diffuse large B-cell lymphoma has been substantially improved by the addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy regimens. We aimed to assess, in patients aged 18-59 years, the potential survival benefit provided by a dose-intensive immunochemotherapy regimen plus rituximab compared with standard treatment plus rituximab. We did an open-label randomised trial comparing dose-intensive rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (R-ACVBP) with subsequent consolidation versus standard rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R-CHOP). Random assignment was done with a computer-assisted randomisation-allocation sequence with a block size of four. Patients were aged 18-59 years with untreated diffuse large B-cell lymphoma and an age-adjusted international prognostic index equal to 1. Our primary endpoint was event-free survival. Our analyses of efficacy and safety were of the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00140595. One patient withdrew consent before treatment and 54 did not complete treatment. After a median follow-up of 44 months, our 3-year estimate of event-free survival was 81% (95% CI 75-86) in the R-ACVBP group and 67% (59-73) in the R-CHOP group (hazard ratio [HR] 0·56, 95% CI 0·38-0·83; p=0·0035). 3-year estimates of progression-free survival (87% [95% CI, 81-91] vs 73% [66-79]; HR 0·48 [0·30-0·76]; p=0·0015) and overall survival (92% [87-95] vs 84% [77-89]; HR 0·44 [0·28-0·81]; p=0·0071) were also increased in the R-ACVBP group. 82 (42%) of 196 patients in the R-ACVBP group experienced a serious adverse event compared with 28 (15%) of 183 in the R-CHOP group. Grade 3-4 haematological toxic effects were more common in the R-ACVBP group, with a higher proportion of patients experiencing a febrile neutropenic episode (38% [75 of 196] vs 9% [16 of 183]). Compared with standard R

  18. Lenalidomide-bendamustine-rituximab in untreated mantle cell lymphoma > 65 years, the Nordic Lymphoma Group phase I+II trial NLG-MCL4

    DEFF Research Database (Denmark)

    Albertsson-Lindblad, Alexandra; Kolstad, Arne; Laurell, Anna;

    2016-01-01

    For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter open-label phase I/II trial we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment to elderly MCL patients. Patients >65 years with untr......For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter open-label phase I/II trial we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment to elderly MCL patients. Patients >65 years...

  19. Toxicity and quality of life after adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): an open-label, multicentre, randomised, phase 3 trial.

    Science.gov (United States)

    de Boer, Stephanie M; Powell, Melanie E; Mileshkin, Linda; Katsaros, Dionyssios; Bessette, Paul; Haie-Meder, Christine; Ottevanger, Petronella B; Ledermann, Jonathan A; Khaw, Pearly; Colombo, Alessandro; Fyles, Anthony; Baron, Marie-Helene; Kitchener, Henry C; Nijman, Hans W; Kruitwagen, Roy F; Nout, Remi A; Verhoeven-Adema, Karen W; Smit, Vincent T; Putter, Hein; Creutzberg, Carien L

    2016-08-01

    About 15% of patients with endometrial cancer have high-risk features and are at increased risk of distant metastases and endometrial cancer-related death. We designed the PORTEC-3 trial to investigate the benefit of adjuvant chemoradiotherapy compared with radiotherapy alone for women with high-risk endometrial cancer. PORTEC-3 was a multicentre, open-label, randomised, international trial. Women with high-risk endometrial cancer were randomly allocated (1:1) to radiotherapy alone (48·6 Gy) in 1·8 Gy fractions five times a week or chemoradiotherapy (two cycles concurrent cisplatin 50 mg/m(2) and four adjuvant cycles of carboplatin area under the curve [AUC] 5 and paclitaxel 175 mg/m(2)) using a biased coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage of cancer, and histological type. The primary endpoints of the PORTEC-3 trial were overall survival and failure-free survival analysed in the intention-to-treat population. This analysis focuses on 2-year toxicity and health-related quality of life as secondary endpoints; analysis was done according to treatment received. Health-related quality of life was assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) the cervix cancer module and chemotherapy and neuropathy subscales of the ovarian cancer module at baseline, after radiotherapy and at 6, 12, 24, 36, and 60 months after randomisation. Adverse events were graded with Common Terminology Criteria for Adverse Events version 3.0. The study was closed on Dec 20, 2013, after achieving complete accrual, and follow-up remains ongoing for the primary outcomes analysis. This trial is registered with ISRCTN.com, number ISRCTN14387080, and with ClinicalTrials.gov, number NCT00411138. Between Sept 15, 2006, and Dec 20, 2013, 686 women were randomly allocated in the PORTEC-3 trial. Of these, 660 met eligibility criteria, and 570 (86%) were evaluable for

  20. Long-term efficacy and safety of oxycodone–naloxone prolonged release in geriatric patients with moderate-to-severe chronic noncancer pain: a 52-week open-label extension phase study

    Directory of Open Access Journals (Sweden)

    Guerriero F

    2016-04-01

    Full Text Available Fabio Guerriero,1,2 Anna Roberto,3 Maria Teresa Greco,4 Carmelo Sgarlata,1 Marco Rollone,2 Oscar Corli3 1Department of Internal Medicine and Medical Therapy, Section of Geriatrics, University of Pavia, 2Department of Geriatrics, Agency for Elderly People of Pavia, Santa Margherita Institute, Pavia, 3Department of Oncology, Pain and Palliative Care Research Unit, IRCCS-Mario Negri Institute for Pharmacological Research, 4Unit of Medical Statistics, Biometry and Epidemiology GA Maccacaro, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy Background: Two-thirds of older people suffer from chronic pain and finding valid treatment options is essential. In this 1-yearlong investigation, we evaluated the efficacy and safety of prolonged-release oxycodone–naloxone (OXN-PR in patients aged ≥70 (mean 81.7 years.Methods: In this open-label prospective study, patients with moderate-to-severe noncancer chronic pain were prescribed OXN-PR for 1 year. The primary endpoint was the proportion of patients who achieved ≥30% reduction in pain intensity after 52 weeks of treatment, without worsening bowel function. The scheduled visits were at baseline (T0, after 4 weeks (T4, and after 52 weeks (T52.Results: Fifty patients completed the study. The primary endpoint was achieved in 78% of patients at T4 and 96% at T52 (P<0.0001. Pain intensity, measured on a 0–10 numerical rating scale, decreased from 6.0 at T0 to 2.8 at T4 and to 1.7 at T52 (P<0.0001. Mean daily dose of oxycodone increased from 10 to 14.4 mg (T4 and finally to 17.4 mg (T52. Bowel Function Index from 35.1 to 28.7 at T52. No changes were observed in cognitive functions (Mini-Mental State Examination evaluation, while daily functioning improved (Barthel Index from 53.1 to 61.0, P<0.0001. The Screener and Opioid Assessment for Patients with Pain-Revised score at 52 weeks was 2.6 (standard deviation 1.6, indicating a low risk of aberrant medication

  1. 两种甘精胰岛素治疗糖尿病的疗效及安全性比较:多中心、随机、开放、对照试验%Efficacy and safety of glargine insulin injection Uslen versus Lantus in diabetic patients: a multicenter, randomized, open-labeled controlled trial

    Institute of Scientific and Technical Information of China (English)

    刘云慧; 侯丽琼; 赵铁耘; 田浩明; 吕肖锋; 杨金奎; 李玲; 朱旅云; 张力辉

    2014-01-01

    Objective To evaluate the efficacy and safety of glargine insulin injection (Uslen) in treatment of diabetic patients.Methods A multicenter,randomized,open-labeled and positive control clinical trial included the patients with type 1 or type 2 diabetes mellitus having poor glucose control after using oral antidiabetic drug or short-acting insulin.All patients were treated with Uslen or Lantus for 16 weeks in two groups by a ratio of 1 ∶ 1.The decreased value and qualification rates of glycated hemoglobin A1 c (HbA1 c) and fasting blood glucose (FBG),the incidence of hypoglycemic and the adverse events were compared pretreatment at the end of 16 weeks' treatment.Results All of 664 cases were randomized into two groups and received therapy (1 ∶ 1).But 623 cases were in complete conformity to design plan,313 cases received Uslen therapy and 310 cases received Lantus therapy.There were no different in age,sex,nation,height and weight between two groups.At the end of 16 weeks' treatment,according to the perprotocol analysis (PPS),the decreased values of HbA1c separately (9.2 ± 1.5)% vs (7.7 ± 1.2)% and (9.3±1.5) vs (7.7±1.1)%,FBGseparately (10.2±2.1 vs7.2±2.0) mmol/Land (10.3±2.3 vs 7.4 ± 2.3) mmol/L were all proved significantly in both Uslen group and Lantus group (all P < 0.001).But the changes of HbA1c(1.5% vs 1.6%,F=0.766,P=0.382) and FBG(3.0 vs 2.9 mmol/L,F=0.280,P =0.597) from baseline to endpoint were similar between the treatment groups (P > 0.05).There were no significant difference in the two groups on the qualification rates of HbA1c(26.2% (82/313)vs 21.3% (66/310),P =0.155) and FBG(29.1% (91/313) vs 28.4% (88/310),P >0.05).There were no significant difference separately 22.7% (75/330) and 22.0% (74/333) on hypoglycemia incidences,and the other adverse events incidences were similar separately 0.3% (1/330 vs 1/333,P > 0.05) in two groups.Conclusion Compared with Lantus,the glargine insulin injection of Uslen has

  2. Prophylactic using of levofloxacin in transrectal prostate biopsy: a prospective, multicenter, randomized, effective drug control and open-label clinical study%左氧氟沙星在经直肠前列腺穿刺围手术期应用的多中心、随机、对照、开放临床研究

    Institute of Scientific and Technical Information of China (English)

    乔庐东; 陈山; 王晓峰; 李清; 杨为民; 牛远杰; 孔垂泽; 王毅; 唐伟

    2014-01-01

    Objective To find an efficacy,safety and economic prophylactic regimen after the transrectal ultrasound-guided prostate biopsy (TRUSPBs) by comparing the results of infection complications after the oral levofloxacin application with other intravenous prophylaxis antibiotics.Methods It was a prospective,randomized,multicenter,effective drug control and open-label clinical study.From October 2011to December 2012,296 patients who had indications of prostate biopsy in 8 medical centers were randomized into two groups:test group (n=150,levofloxacin,500 mg,po,qd for 3 days) and control group (n=146 intravenous antibiotics of any kinds,3 days).All those antibiotics were used on the day of biopsy and within two days after the biopsy.The average age in test group and control group was (67.6±8.6) years vs (68.7± 8.8) years,the average PSA level in test group and control group was (105.8±638.1) μg/L vs (174.6±861.4) μg/L,respectively (P>0.05).In test group and control group,the mean duration of present illness was (0.6±2.3) months and (0.4± 1.2) months.The positive rate after the digital rectal examination was 45.3% (68/150) in test group and 51.4% (75/146) in control group.All patients underwent TRUSPB.The infectious complications and the expenditure of medicine in two groups were compared.Results The occurrences of infection complications in test group and control group were 6.0% (9/150) and 6.2% (9/146).Meanwhile,the rate of asymptomatic bacteriuria was 4.7% (7/150) in test group and 3.4% (5/146) in control group.In those groups,the rate of symptomatic urinary tract infection was 0 vs 0.7% (1/146),the rate of fever was 0 vs 0.7% (1/146),the rate of bacteremia was 1.3% (2/150) vs 0 and the rate of urosepsis was 0 vs 1.4% (2/146),respectively (P>0.05).The average costs of medicine in test group and control group were (43.0±3.8) yuan and (403.7±277.6) yuan,respectively (P<0.05).Conclusions Levofloxacin (500 mg,po,qd for 3 days) is an

  3. Inactivated poliovirus vaccine given alone or in a sequential schedule with bivalent oral poliovirus vaccine in Chilean infants: a randomised, controlled, open-label, phase 4, non-inferiority study.

    Science.gov (United States)

    O'Ryan, Miguel; Bandyopadhyay, Ananda S; Villena, Rodolfo; Espinoza, Mónica; Novoa, José; Weldon, William C; Oberste, M Steven; Self, Steve; Borate, Bhavesh R; Asturias, Edwin J; Clemens, Ralf; Orenstein, Walter; Jimeno, José; Rüttimann, Ricardo; Costa Clemens, Sue Ann

    2015-11-01

    Bivalent oral poliovirus vaccine (bOPV; types 1 and 3) is expected to replace trivalent OPV (tOPV) globally by April, 2016, preceded by the introduction of at least one dose of inactivated poliovirus vaccine (IPV) in routine immunisation programmes to eliminate vaccine-associated or vaccine-derived poliomyelitis from serotype 2 poliovirus. Because data are needed on sequential IPV-bOPV schedules, we assessed the immunogenicity of two different IPV-bOPV schedules compared with an all-IPV schedule in infants. We did a randomised, controlled, open-label, non-inferiority trial with healthy, full-term (>2·5 kg birthweight) infants aged 8 weeks (± 7 days) at six well-child clinics in Santiago, Chile. We used supplied lists to randomly assign infants (1:1:1) to receive three polio vaccinations (IPV by injection or bOPV as oral drops) at age 8, 16, and 24 weeks in one of three sequential schedules: IPV-bOPV-bOPV, IPV-IPV-bOPV, or IPV-IPV-IPV. We did the randomisation with blocks of 12 stratified by study site. All analyses were done in a masked manner. Co-primary outcomes were non-inferiority of the bOPV-containing schedules compared with the all-IPV schedule for seroconversion (within a 10% margin) and antibody titres (within two-thirds log2 titres) to poliovirus serotypes 1 and 3 at age 28 weeks, analysed in the per-protocol population. Secondary outcomes were seroconversion and titres to serotype 2 and faecal shedding for 4 weeks after a monovalent OPV type 2 challenge at age 28 weeks. Safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01841671, and is closed to new participants. Between April 25 and August 1, 2013, we assigned 570 infants to treatment: 190 to IPV-bOPV-bOPV, 192 to IPV-IPV-bOPV, and 188 to IPV-IPV-IPV. 564 (99%) were vaccinated and included in the intention-to-treat cohort, and 537 (94%) in the per-protocol analyses. In the IPV-bOPV-bOPV, IPV-IPV-bOPV, and IPV-IPV-IPV groups

  4. Open-Label Memantine in Fragile X Syndrome

    Science.gov (United States)

    Erickson, Craig A.; Mullett, Jennifer E.; McDougle, Christopher J.

    2009-01-01

    Glutamatergic dysfunction is implicated in the pathophysiology of fragile X syndrome (FXS). The purpose of this pilot study was to examine the effectiveness and tolerability of memantine for a number of target symptoms associated with FXS. Medical records describing open-label treatment with memantine in 6 patients with FXS and a comorbid…

  5. A single-arm, open-label, phase 2 clinical trial evaluating disease response following treatment with BI-505, a human anti-intercellular adhesion molecule-1 monoclonal antibody, in patients with smoldering multiple myeloma

    Science.gov (United States)

    Wichert, Stina; Juliusson, Gunnar; Johansson, Åsa; Sonesson, Elisabeth; Teige, Ingrid; Wickenberg, Anna Teige; Frendeus, Björn; Korsgren, Magnus; Hansson, Markus

    2017-01-01

    Background Smoldering multiple myeloma (SMM) is an indolent disease stage, considered to represent the transition phase from the premalignant MGUS (Monoclonal Gammopathy of Undetermined Significance) state towards symptomatic multiple myeloma (MM). Even though this diagnosis provides an opportunity for early intervention, few treatment studies have been done and the current standard of care is observation until progression. BI-505, a monoclonal antibody directed against intercellular adhesion molecule 1 (ICAM-1) with promising anti-myeloma activity in preclinical trials, is a possible treatment approach for this patient category with potential to eliminate tumor cells with minimal long-term side effects. BI-505 was well tolerated in an earlier phase 1 trial. Methods and findings In this phase 2 trial the effects of BI-505 in patients with SMM were studied. Four patients were enrolled and three of them completed the first cycle of treatment defined as 5 doses of BI-505, a total of 43 mg/kg BW, over a 7-week period. In the three evaluable patients, BI-505 showed a benign safety profile. None of the patients achieved a response as defined per protocol. EudraCT number: 2012-004884-29. Conclusions The study was conducted to assess the efficacy, safety and pharmacodynamics of BI-505 in patients with SMM. BI-505 showed no clinically relevant efficacy on disease activity in these patients with SMM, even if well tolerated. Trial registration ClinicalTrials.gov Identifier: NCT01838369. PMID:28158311

  6. A 10-Month, Open-Label Evaluation of Desvenlafaxine in Outpatients With Major Depressive Disorder

    Science.gov (United States)

    Pitrosky, Bruno; Padmanabhan, S. Krishna; Rosas, Gregory R.

    2011-01-01

    Background: The primary objective was to evaluate the long-term safety of desvenlafaxine (administered as desvenlafaxine succinate) during open-label treatment in adult outpatients with a primary DSM-IV diagnosis of major depressive disorder (MDD). Method: Depressed adult outpatients (≥ 18 years) who had completed 8-week, double-blind therapy (desvenlafaxine, venlafaxine extended release, or placebo) in a phase 3 study of desvenlafaxine for MDD received up to 10 months of open-label treatment with flexible-dose desvenlafaxine (200 to 400 mg/d). Safety assessments included physical examination, measurement of weight and vital signs, laboratory determinations, and 12-lead electrocardiogram recordings. Adverse events (AEs) and discontinuations due to AEs were monitored throughout the trial. The primary efficacy outcome was mean change from baseline on 17-item Hamilton Depression Rating Scale (HDRS-17) total score. The trial was conducted from August 2003 to March 2006. Results: The safety population included 1,395 patients who took at least 1 dose of open-label desvenlafaxine. Treatment-emergent AEs were reported by 1,238 of 1,395 patients (89%) during the open-label, on-therapy period. Treatment-emergent AEs reported by 10% or more patients were headache, nausea, hyperhidrosis, dizziness, dry mouth, insomnia, upper respiratory infection, nasopharyngitis, and fatigue. Adverse events were the primary reason for study discontinuation in 296 of 1,395 patients (21%). Ten patients (Desvenlafaxine can be safely administered for up to 12 months. No new safety findings were observed in this study. Trial Registration: clinicaltrials.gov Identifier: NCT01309542 PMID:21977353

  7. Clinical efficacy of zanolimumab (HuMax-CD4): two phase 2 studies in refractory cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Kim, Youn H; Duvic, Madeleine; Obitz, Erik

    2007-01-01

    The efficacy and safety of zanolimumab in patients with refractory cutaneous T-cell lymphoma (CTCL) have been assessed in two phase 2, multicenter, prospective, open-label, uncontrolled clinical studies. Patients with treatment refractory CD4(+) CTCL (mycosis fungoides [MF], n = 38; Sézary syndrome...

  8. The lipid-lowering effects of lomitapide are unaffected by adjunctive apheresis in patients with homozygous familial hypercholesterolaemia – a post-hoc analysis of a Phase 3, single-arm, open-label trial

    Science.gov (United States)

    Stefanutti, C; Blom, DJ; Averna, MR; Meagher, EA; Theron, HdT; Marais, AD; Hegele, RA; Sirtori, CR; Shah, PK; Gaudet, D; Vigna, GB; Sachais, BS; Di Giacomo, S; du Plessis, AME; Bloedon, LT; Balser, J; Rader, DJ; Cuchel, M

    2015-01-01

    Objective Lomitapide (a microsomal triglyceride transfer protein inhibitor) is an adjunctive treatment for homozygous familial hypercholesterolaemia (HoFH), a rare genetic condition characterised by elevated low-density lipoprotein-cholesterol (LDL-C), and premature, severe, accelerated atherosclerosis. Standard of care for HoFH includes lipid-lowering drugs and lipoprotein apheresis. We conducted a post-hoc analysis using data from a Phase 3 study to assess whether concomitant apheresis affected the lipid-lowering efficacy of lomitapide. Methods Existing lipid-lowering therapy, including apheresis, was to remain stable from Week −6 to Week 26. Lomitapide dose was escalated on the basis of individual safety/tolerability from 5 mg to 60 mg a day (maximum). The primary endpoint was mean percent change in LDL-C from baseline to Week 26 (efficacy phase), after which patients remained on lomitapide through Week 78 for safety assessment and further evaluation of efficacy. During this latter period, apheresis could be adjusted. We analysed the impact of apheresis on LDL-C reductions in patients receiving lomitapide. Results Of the 29 patients that entered the efficacy phase, 18 (62%) were receiving apheresis at baseline. Twenty-three patients (13 receiving apheresis) completed the Week 26 evaluation. Of the six patients who discontinued in the first 26 weeks, five were receiving apheresis. There were no significant differences in percent change from baseline of LDL-C at Week 26 in patients treated (−48%) and not treated (−55%) with apheresis (p=0.545). Changes in Lp(a) levels were modest and not different between groups (p=0.436). Conclusion The LDL-C lowering efficacy of lomitapide is unaffected by lipoprotein apheresis. PMID:25897792

  9. In Vitro Activity of Ceftazidime-Avibactam against Isolates in a Phase 3 Open-Label Clinical Trial for Complicated Intra-Abdominal and Urinary Tract Infections Caused by Ceftazidime-Nonsusceptible Gram-Negative Pathogens.

    Science.gov (United States)

    Stone, Gregory G; Bradford, Patricia A; Newell, Paul; Wardman, Angela

    2017-02-01

    The in vitro activity of ceftazidime-avibactam was evaluated against 341 Gram-negative isolates from 333 patients in a randomized, phase 3 clinical trial of patients with complicated urinary tract or intra-abdominal infections caused by ceftazidime-nonsusceptible pathogens (NCT01644643). Ceftazidime-avibactam MIC90 values against Enterobacteriaceae and Pseudomonas aeruginosa (including several class B or D enzyme producers that avibactam does not inhibit) were 1 and 64 μg/ml, respectively. Overall, the ceftazidime-avibactam activity against ceftazidime-nonsusceptible isolates was comparable to the activity of ceftazidime-avibactam previously reported against ceftazidime-susceptible isolates. (This study has been registered at ClinicalTrials.gov under identifier NCT01644643.).

  10. The antibacterial substance, taurolidine in the second/third-line treatment of very advanced stage IV melanoma including brain metastases: results of a phase 2, open-label study.

    Science.gov (United States)

    Imhof, Laurence; Goldinger, Simone M; Baumann, Katrin; Schad, Karin; French, Lars E; Röthlisberger, Peter; Dummer, Reinhard

    2011-02-01

    The efficacy and tolerability of taurolidine, an antibacterial substance, was evaluated in a phase 2 trial enrolling patients with advanced melanoma. The treatment schedule consisted of daily taurolidine (20 g) administered intravenously for 5 days per week for 3 consecutive weeks followed by 1 week of rest. One cycle comprised of 28 days. A maximum of six cycles could be administered. Sixteen patients were assessable for tumor response, seven of whom had brain metastases. Three patients (18.8%) achieved disease stabilization, including a patient with a primary mucosal melanoma of the nasal cavity who had a marked locoregional response with disease stabilization of the distant metastases. Thirteen patients had disease progression. Median overall survival was 46±1 days. Adverse events were moderate and mainly gastrointestinal. Treatment with taurolidine has no activity in patients with advanced melanoma.

  11. Randomized, controlled, open-label, non-inferiority study of the CONSORT algorithm for individualized dosing of follitropin alfa

    NARCIS (Netherlands)

    Olivennes, F.; Trew, G.; Borini, A.; Broekmans, F.; Arriagada, P.; Warne, D. W.; Howles, C. M.

    2015-01-01

    In this randomized, controlled, open-label, phase IV study, ovarian response after a follitropin alfa starting dose determined by the CONSORT calculator was compared with a standard dose (150 IU). Normo-ovulatory women (aged 18-34 years) eligible for assisted reproductive techniques were recruited (

  12. Phase II open-label study of erlotinib in combination with gemcitabine in unresectable and/or metastatic adenocarcinoma of the pancreas: relationship between skin rash and survival (Pantar study).

    Science.gov (United States)

    Aranda, E; Manzano, J L; Rivera, F; Galán, M; Valladares-Ayerbes, M; Pericay, C; Safont, M J; Mendez, M J; Irigoyen, A; Arrivi, A; Sastre, J; Díaz-Rubio, E

    2012-07-01

    Skin rash is an adverse event which might be associated with longer survival in patients treated with epidermal growth factor receptor tyrosine kinase inhibitors. The aim of this nonrandomised phase II clinical trial is to prospectively evaluate the relationship between skin rash and overall survival (OS) in advanced/metastatic pancreatic cancer treated with erlotinib plus gemcitabine. Patients were given gemcitabine (1000 mg/m2/week, 3 weeks every 4 weeks) plus erlotinib (100 mg/day orally continuously) until disease progression/unacceptable toxicity. The primary end point was OS. A total of 153 eligible patients were enrolled (grade≥2 rash, 25%; grade<2 rash, 75%). OS was longer in patients with grade≥2 rash versus grade<2 (11 versus 5 months; P<0.001). Progression-free survival was longer in patients with grade≥2 rash versus grade<2 (6 versus 3 months; P<0.001) and shorter in those without rash versus grade 1 (2 versus 4 months; P=0.005) or grade≥2 (2 versus 6 months; P<0.001). Patients with grade≥2 rash showed higher rates of overall response (21% versus 7%; P<0.05) and disease control (84% versus 43%; P<0.05) versus grade<2. This study prospectively confirms the relationship between rash and longer OS in unresectable locally advanced/metastatic pancreatic cancer treated with erlotinib plus gemcitabine.

  13. Impact of renal impairment on outcomes with lenalidomide and dexamethasone treatment in the FIRST trial, a randomized, open-label phase 3 trial in transplant-ineligible patients with multiple myeloma.

    Science.gov (United States)

    Dimopoulos, Meletios A; Cheung, Matthew C; Roussel, Murielle; Liu, Ting; Gamberi, Barbara; Kolb, Brigitte; Derigs, H Guenter; Eom, HyeonSeok; Belhadj, Karim; Lenain, Pascal; Van der Jagt, Richard; Rigaudeau, Sophie; Dib, Mamoun; Hall, Rachel; Jardel, Henry; Jaccard, Arnaud; Tosikyan, Axel; Karlin, Lionel; Bensinger, William; Schots, Rik; Leupin, Nicolas; Chen, Guang; Marek, Jennifer; Ervin-Haynes, Annette; Facon, Thierry

    2016-03-01

    Renal impairment is associated with poor prognosis in myeloma. This analysis of the pivotal phase 3 FIRST trial examined the impact of renally adapted dosing of lenalidomide and dexamethasone on outcomes of patients with different degrees of renal impairment. Transplant-ineligible patients not requiring dialysis were randomized 1:1:1 to receive continuous lenalidomide and dexamethasone until disease progression (n=535) or for 18 cycles (72 weeks; n=541), or melphalan, prednisone, and thalidomide for 12 cycles (72 weeks; n=547). Follow-up is ongoing. Patients were grouped by baseline creatinine clearance into no (≥ 80 mL/min [n=389]), mild (≥ 50 to < 80 mL/min [n=715]), moderate (≥ 30 to < 50 mL/min [n=372]), and severe impairment (< 30 mL/min [n=147]) subgroups. Continuous lenalidomide and dexamethasone therapy reduced the risk of progression or death in no, mild, and moderate renal impairment subgroups vs. melphalan, prednisone, and thalidomide therapy (HR = 0.67, 0.70, and 0.65, respectively). Overall survival benefits were observed with continuous lenalidomide and dexamethasone treatment vs. melphalan, prednisone, and thalidomide treatment in no or mild renal impairment subgroups. Renal function improved from baseline in 52.6% of lenalidomide and dexamethasone-treated patients. The safety profile of continuous lenalidomide and dexamethasone was consistent across renal subgroups, except for grade 3/4 anemia and rash, which increased with increasing severity of renal impairment. Continuous lenalidomide and dexamethasone treatment, with renally adapted lenalidomide dosing, was effective for most transplant-ineligible patients with myeloma and renal impairment. Trial registration: ClinicalTrials.gov (NCT00689936); EudraCT (2007-004823-39). Funding: Intergroupe Francophone du Myélome and the Celgene Corporation. Copyright© Ferrata Storti Foundation.

  14. Safety, Tolerability, and Preliminary Activity of LB-100, an Inhibitor of Protein Phosphatase 2A, in Patients with Relapsed Solid Tumors: An Open-Label, Dose Escalation, First-in-Human, Phase I Trial.

    Science.gov (United States)

    Chung, Vincent; Mansfield, Aaron S; Braiteh, Fadi; Richards, Donald; Durivage, Henry; Ungerleider, Richard S; Johnson, Francis; Kovach, John S

    2017-07-01

    Purpose: To determine the MTD and to assess the safety, tolerability, and potential activity of LB-100, a first-in-class small-molecule inhibitor of protein phosphatase 2A (PP2A) in adult patients with progressive solid tumors.Experimental Design: LB-100 was administered intravenously daily for 3 days in 21-day cycles in a 3 + 3 dose escalation design.Results: There were 29 patient entries over 7 dose escalations. One patient stopped treatment after one dose because of an acute infection and was reenrolled after recovery; each course was analyzed as a separate patient entry. Two patients had dose-limiting toxicity (reversible increases in serum creatinine or calculated serum creatinine clearance) at the 3.1 mg/m(2) level. Probable or possible study drug-related grade 3 adverse events occurred in 6 (20.7%) patients [anemia (n = 2), decreased creatinine clearance, dyspnea, hyponatremia, and lymphopenia]. Ten (50%) of 20 response-evaluable patients had stable disease for four or more cycles. One patient with pancreatic adenocarcinoma had a partial response noted after 10 cycles, which was maintained for five additional cycles. The other patients achieving stable disease had one of the following: fibrosarcoma, chondrosarcoma, thymoma, atypical carcinoid of lung, or ovarian, testicular, breast (n = 2), and prostate cancer. The recommended phase II dose of LB-100 is 2.33 mg/m(2) daily for 3 days every 3 weeks.Conclusions: The safety, tolerability, preliminary evidence of antitumor activity, and novel mechanism of action of LB-100 support its continued development alone and in combination with other therapies. Clin Cancer Res; 23(13); 3277-84. ©2016 AACR. ©2016 American Association for Cancer Research.

  15. Impact of renal impairment on outcomes with lenalidomide and dexamethasone treatment in the FIRST trial, a randomized, open-label phase 3 trial in transplant-ineligible patients with multiple myeloma

    Science.gov (United States)

    Dimopoulos, Meletios A.; Cheung, Matthew C.; Roussel, Murielle; Liu, Ting; Gamberi, Barbara; Kolb, Brigitte; Derigs, H. Guenter; Eom, HyeonSeok; Belhadj, Karim; Lenain, Pascal; Van der Jagt, Richard; Rigaudeau, Sophie; Dib, Mamoun; Hall, Rachel; Jardel, Henry; Jaccard, Arnaud; Tosikyan, Axel; Karlin, Lionel; Bensinger, William; Schots, Rik; Leupin, Nicolas; Chen, Guang; Marek, Jennifer; Ervin-Haynes, Annette; Facon, Thierry

    2016-01-01

    Renal impairment is associated with poor prognosis in myeloma. This analysis of the pivotal phase 3 FIRST trial examined the impact of renally adapted dosing of lenalidomide and dexamethasone on outcomes of patients with different degrees of renal impairment. Transplant-ineligible patients not requiring dialysis were randomized 1:1:1 to receive continuous lenalidomide and dexamethasone until disease progression (n=535) or for 18 cycles (72 weeks; n=541), or melphalan, prednisone, and thalidomide for 12 cycles (72 weeks; n=547). Follow-up is ongoing. Patients were grouped by baseline creatinine clearance into no (≥ 80 mL/min [n=389]), mild (≥ 50 to < 80 mL/min [n=715]), moderate (≥ 30 to < 50 mL/min [n=372]), and severe impairment (< 30 mL/min [n=147]) subgroups. Continuous lenalidomide and dexamethasone therapy reduced the risk of progression or death in no, mild, and moderate renal impairment subgroups vs. melphalan, prednisone, and thalidomide therapy (HR = 0.67, 0.70, and 0.65, respectively). Overall survival benefits were observed with continuous lenalidomide and dexamethasone treatment vs. melphalan, prednisone, and thalidomide treatment in no or mild renal impairment subgroups. Renal function improved from baseline in 52.6% of lenalidomide and dexamethasone–treated patients. The safety profile of continuous lenalidomide and dexamethasone was consistent across renal subgroups, except for grade 3/4 anemia and rash, which increased with increasing severity of renal impairment. Continuous lenalidomide and dexamethasone treatment, with renally adapted lenalidomide dosing, was effective for most transplant-ineligible patients with myeloma and renal impairment. PMID:26659916

  16. Single-dose pharmacokinetics of co-crystal of tramadol-celecoxib: Results of a four-way randomized open-label phase I clinical trial in healthy subjects.

    Science.gov (United States)

    Videla, Sebastián; Lahjou, Mounia; Vaqué, Anna; Sust, Mariano; Encabo, Mercedes; Soler, Lluis; Sans, Artur; Sicard, Eric; Gascón, Neus; Encina, Gregorio; Plata-Salamán, Carlos

    2017-08-15

    Co-crystal of tramadol-celecoxib (CTC) is a novel co-crystal molecule containing two active pharmaceutical ingredients under development by Esteve (E-58425) and Mundipharma Research (MR308). This Phase I study compared single-dose pharmacokinetics (PK) of CTC with those of the individual reference products [immediate-release (IR) tramadol and celecoxib] alone and in open combination. Healthy adults aged 18-55 years were orally administered four treatments under fasted conditions (separated by 7-day wash-out period): 200 mg IR CTC (equivalent to 88 mg tramadol and 112 mg celecoxib; Treatment 1); 100 mg IR tramadol (Treatment 2); 100 mg celecoxib (Treatment 3); and 100 mg IR tramadol and 100 mg celecoxib (Treatment 4). Treatment sequence was assigned using computer-generated randomization. PK parameters were calculated using noncompartmental analysis with parameters for CTC adjusted according to reference product dose (100 mg). Thirty-six subjects (28 male, mean age 36 years) participated. Tramadol PK parameters for Treatments-1, -2 and -4, respectively, were 263, 346 and 349 ng ml(-1) (mean maximum plasma concentration); 3039, 2979 and 3119 ng h ml(-1) (mean cumulative area under the plasma concentration-time curve); and 2.7, 1.8 and 1.8 h (median time to maximum plasma concentration). For Treatments 1, 3 and 4, the respective celecoxib PK parameters were 313, 449 and 284 ng ml(-1) ; 2183, 3093 and 2856 ng h ml(-1) ; and 1.5, 2.3 and 3.0 h. No unexpected adverse events were reported. PK parameters of each API in CTC were modified by co-crystallization compared with marketed formulations of tramadol, celecoxib, and their open combination. © 2017 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

  17. Treatment, rationale, and study design of TALISMAN study: a randomized phase II open-label study of second-line erlotinib versus intermittent erlotinib dosing with docetaxel in the treatment of former-smoker men affected by recurrent squamous non-small-cell lung cancer.

    Science.gov (United States)

    Gridelli, Cesare; Rossi, Antonio; Venturino, Paola; de Marinis, Filippo

    2011-01-01

    We present the treatment rationale and study design of the TALISMAN (TArceva and docetaxeL In former-Smokers MAle patients with recurrent Non-small-cell lung cancer) study, an open-label, randomized phase II trial of erlotinib (arm A) or intermittent erlotinib and docetaxel (arm B) in male former smokers affected by recurrent squamous non-small-cell lung cancer (NSCLC). In arm A, treatment consists of erlotinib 150 mg daily orally until progression or inacceptable toxicity; in arm B, treatment consists of docetaxel 75 mg/m² on day 1 and erlotinib 150 mg orally on days 2-16, recycled every 3 weeks up to 4 cycles followed, in patients not progressed, by erlotinib 150 mg daily orally until disease progression or inacceptable toxicity. The primary endpoint of this study is the rate of patients without progression at 6 months, and secondary objectives include median progression-free survival, median overall survival, activity, and toxicity. In addition, translational research evaluating EGFR and KRAS mutational status will be investigated for both arms.

  18. Cyclosporine C2 monitoring for the treatment of frequently relapsing nephrotic syndrome in children: a multicenter randomized phase II trial.

    Science.gov (United States)

    Iijima, Kazumoto; Sako, Mayumi; Oba, Mari Saito; Ito, Shuichi; Hataya, Hiroshi; Tanaka, Ryojiro; Ohwada, Yoko; Kamei, Koichi; Ishikura, Kenji; Yata, Nahoko; Nozu, Kandai; Honda, Masataka; Nakamura, Hidefumi; Nagata, Michio; Ohashi, Yasuo; Nakanishi, Koichi; Yoshikawa, Norishige

    2014-02-01

    An open-label, multicenter, randomized phase II trial was conducted from July 1, 2005 to March 29, 2011 to compare two protocols for treating children with frequently relapsing nephrotic syndrome using microemulsified cyclosporine. Ninety-three children with frequently relapsing nephrotic syndrome were randomly assigned to group A (n=46) or group B (n=47). In both groups, the 2-hour postdose cyclosporine level was monitored. For group A, the cyclosporine target was set to 600-700 ng/ml for the first 6 months and 450-550 ng/ml for the next 18 months; for group B, it was set to 450-550 ng/ml for the first 6 months and 300-400 ng/ml for the next 18 months. The primary end point was the sustained remission rate. At the end of the study, if there was no difference in safety profile between the two groups and the sustained remission rate in group A was superior to group B with a decision threshold of 8%, then the regimen for group A would be determined the better treatment. Eight children from an ineligible institution, where cyclosporine levels were not measured, were excluded from all analyses. At 24 months, the sustained remission rate was nonsignificantly higher in group A (n=43) than group B (n=42; 64.4% versus 50.0%; hazard ratio, 0.57; 95% confidence interval, 0.29 to 1.11; P=0.09), and the progression-free survival rate was significantly higher (88.1% versus 68.4%; hazard ratio, 0.33; 95% confidence interval, 0.12 to 0.94; P=0.03). The relapse rate was significantly lower in group A than group B (0.41 versus 0.95 times/person-year; hazard ratio, 0.43; 95% confidence interval, 0.19 to 0.84; P=0.02). The rate and severity of adverse events were similar in both treatment groups. The sustained remission rate was not significantly different between the two treatment groups, but the regimen with the higher 2-hour postdose cyclosporine level target improved progression-free survival and reduced the relapse rate.

  19. A phase 2 multi-center, open-label, switch-over trial to evaluate the safety and efficacy of Abcertin® in patients with type 1 Gaucher disease.

    Science.gov (United States)

    Choi, Jin-Ho; Lee, Beom Hee; Ko, Jung Min; Sohn, Young Bae; Lee, Jin-Sung; Kim, Gu-Hwan; Heo, Sun Hee; Park, June-Young; Kim, Yoo-Mi; Kim, Ja-Hye; Yoo, Han-Wook

    2015-04-01

    Gaucher disease is a lysosomal storage disease for which enzyme replacement therapy has proven to be effective. A switch-over clinical trial was performed to evaluate the efficacy and safety of Abcertin® (ISU Abxis, Seoul, Korea) in subjects with type 1 Gaucher disease who were previously treated with imiglucerase. Five Korean patients with type 1 Gaucher disease were enrolled. Previous doses of imiglucerase ranged from 30 to 55 U/kg every other week. The same dose of Abcertin® was administered to all patients for 24 weeks. Primary efficacy endpoints were changes in hemoglobin levels and platelet counts, and the secondary efficacy endpoints included changes in liver and spleen volumes, serum biomarkers, skeletal status and bone mineral density (BMD). During the study period, no statistically significant changes were observed in all parameters including hemoglobin levels and platelet counts, liver and spleen volumes, skeletal status and BMD. Abcertin® administration was continued in three patients for another 24 weeks as an extension of the study. Hemoglobin levels and platelet counts were maintained in all three patients. In conclusion, the efficacy and safety of Abcertin® are similar to those of imiglucerase, and Abcertin® is an effective therapeutic agent for patients with type 1 Gaucher disease (Clinical Trial Registry No. NCT02053896 at www.clinicaltrials.gov).

  20. A Single-arm, Multicenter, Open-label Phase 2 Study of Lapatinib as the Second-line Treatment of Patients With Locally Advanced or Metastatic Transitional Cell Carcinoma

    NARCIS (Netherlands)

    C. Wülfing; J.P.H. Machiels; D.J. Richel; M.O. Grimm; U. Treiber; M.R. de Groot; P. Beuzeboc; R. Parikh; F. Pétavy; I.A. El-Hariry

    2009-01-01

    BACKGROUND: The treatment of recurrent transitional cell carcinoma (TCC) remains an unmet clinical need. This study assessed lapatinib, a dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and HER-2, as second-line therapy in patients with locally advanced or metastatic TCC. M

  1. An Open-Label, Randomized Study of a 9-Valent Human Papillomavirus Vaccine Given Concomitantly with Diphtheria, Tetanus, Pertussis, and Poliomyelitis Vaccines to Healthy Adolescents 11 to 15 Years of Age

    DEFF Research Database (Denmark)

    Kosalaraksa, Pope; Mehlsen, Jesper; Vesikari, Timo

    2015-01-01

    (diphtheria, tetanus, acellular pertussis, and inactivated poliomyelitis vaccine). METHODS: This open-label, randomized, multicenter study enrolled 1054 males and females ages 11-15 years. Subjects were randomly assigned to each group in a 1:1 ratio. Subjects received a 0.5mL dose of 9vHPV vaccine...

  2. 奥氮平换用齐拉西酮治疗精神分裂症的安全性和有效性研究%Switching from olanzapine to ziprasidone: a 12-Week, open-label, multicenter study evaluating the effectiveness and safety of ziprasidone in patients with schizophrenia.

    Institute of Scientific and Technical Information of China (English)

    段艳平; 司天梅; 苏允爱; 党卫民; 邓红; 陈红辉; 刘铁榜; 陶明

    2013-01-01

    Objective To evaluate the effectiveness and safety of switching to ziprasidone from olanzapine because of inadequate response or intolerance. Methods A total of 100 patients with first-episode or non-refractory schizophrenia (diagnosed according with the criteria of DSM-IV) who had no response to olanzapine or showed poor tolerance to alanzapine were enrolled in a 12-week, open-label, flexible-dose ziprasidone trial. All patients were assessed with Positive and Negative Syndrome Scale (PANSS) , Calgary Depression Scale (CDSS) , global impression scale (CGI) and Social Functions ( SF-12) at baseline and the end of 2nd, 4th, 8th, 12th week to evaluate the efficacy. Extrapyramidal Side Effects Scale (SAS) , laboratory examination and electrocardiogram examination were performed to evaluate the safety at baseline and the end of the 4th, 8th week of the treatment. Results A total of 86 patients completed the trial. Scores of PANSS, CDSS, CGI and SF-12 all decreased significantly with the advance of the treatment (P <0. 001). 61 complete records of adverse reactions were collected. The most common adverse reaction was extrapyramidal effect (32 cases, 36. 07%). The prevalence of relatively rare adverse reactions was 16. 39% (10 cases) , which consisted of agitation (2 cases) , nausea (1 case) , constipation (1 case) , insomnia (1 case) , dizziness (1 case) , headache (1 case) , anxiety (1 case) , dry mouth ( 1 case) and tachycardia ( 1 case). There were no significant changes in fasting glucose, HbAlc, triglyceride, total cholesterol, prolactin, QTc interval, heart rate at different observation time-points with the advance of the treatment. Conclusion Ziprasidone can improve the clinical symptoms effectively in patients who had no response to olanzapine or showed poor tolerance to alanzapine. Ziprasidone has less adverse reactions and has little effect on metabolism.%目的 观察不能耐受奥氮平治疗或经奥氮平治疗无效的精神分裂症

  3. Maintenance of Clinical and Radiographic Benefit With Intravenous Golimumab Therapy in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy: Week-112 Efficacy and Safety Results of the Open-Label Long-Term Extension of a Phase III, Double-Blind, Randomized, Placebo-Controlled Trial.

    Science.gov (United States)

    Bingham, Clifton O; Mendelsohn, Alan M; Kim, Lilianne; Xu, Zhenhua; Leu, Jocelyn; Han, Chenglong; Lo, Kim Hung; Westhovens, Rene; Weinblatt, Michael E

    2015-12-01

    To evaluate the safety, efficacy, pharmacokinetics, immunogenicity, and radiographic progression through 2 years of treatment with intravenous (IV) golimumab plus methotrexate (MTX) in an open-label extension of a phase III trial of patients with active rheumatoid arthritis (RA) despite MTX therapy. In the phase III, double-blind, randomized, placebo-controlled GO-FURTHER trial, 592 patients with active RA were randomized (2:1) to intravenous golimumab 2 mg/kg plus MTX (Group 1) or placebo plus MTX (Group 2) at weeks 0 and 4, then every 8 weeks thereafter; placebo patients crossed over to golimumab at week 16 (early escape) or week 24 (crossover). The final golimumab infusion was at week 100. Assessments included American College of Rheumatology 20%, 50%, 70% (ACR20, ACR50, ACR70) response criteria, 28-joint count disease activity score using the C-reactive protein level (DAS28-CRP), physical function and quality of life measures, and changes in the modified Sharp/van der Heijde scores (SHS). Safety was monitored through week 112. In total, 486 patients (82.1%) continued treatment through week 100, and 68.1%, 43.8%, and 23.5% had an ACR20/50/70 response, respectively, at week 100. Clinical response and improvements in physical function and quality of life were generally maintained from week 24 through 2 years. Mean change from baseline to week 100 in SHS score was 0.74 in Group 1 and 2.10 in Group 2 (P = 0.005); progression from week 52 to week 100 was clinically insignificant in both groups. A total of 481 patients completed the safety followup through week 112; 79.1% had an adverse event, and 18.2% had a serious adverse event. Clinical response to IV golimumab plus MTX was maintained through week 100. Radiographic progression following golimumab treatment was clinically insignificant between week 52 and week 100. No unexpected adverse events occurred through week 112, and the safety profile was consistent with anti-tumor necrosis factor therapy. © 2015 The

  4. "Burst" ketamine for refractory cancer pain: an open-label audit of 39 patients.

    Science.gov (United States)

    Jackson, K; Ashby, M; Martin, P; Pisasale, M; Brumley, D; Hayes, B

    2001-10-01

    The results of a novel approach to the use of ketamine in refractory cancer pain are reported. In this prospective, multicenter, unblinded, open-label audit, 39 patients (with a total of 43 pains) received a short duration (3 to 5 days) ketamine infusion. The initial dose of 100 mg/24 hr was escalated if required to 300 mg/24 hr and then to a maximum dose of 500 mg/24hr. The overall response rate was 29/43 (67%). Analysis of results according to pain mechanisms showed that 15/17 somatic and 14/23 neuropathic pains responded. In 5 patients who appeared to respond, it is possible that another concurrent intervention may have contributed in whole or part for the pain relief observed. After cessation of ketamine, 24/29 maintained good pain control, with a maximum documented duration of eight weeks. However, 5 of the initial 29 responders experienced a recurrence of pain within 24 hours, and ketamine was recommenced. Of these, 2 underwent another intervention for pain control while 3 continued on ketamine until their deaths between two and four weeks later. Twelve patients reported adverse psychomimetic effects, with the incidence rising with increasing dose. Four of these were non-responders and the ketamine was stopped. Eight were responders, and in 3 the adverse effects were rendered acceptable with dose reduction; the other 5 rejected a dose reduction. The results reported suggest the need for further investigation of the place of ketamine in cancer pain management.

  5. Open label trial of granulocyte apheresis suggests therapeutic efficacy in chronically active steroid refractory ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Wolfgang Kruis; Robert L(o)fberg; Axel Dignass; Elisabeth Steinhagen-Thiessen; Julia Morgenstern; Joachim M(o)ssner; Stephan Schreiber; Maurizio Vecchi; Alberto Malesci; Max Reinshagen

    2005-01-01

    AIM:To study the efficacy, safety, and feasibility of a granulocyte adsorptive type apheresis system for the treatment of patients with chronically active ulcerative colitis despite standard therapy.METHODS: An open label multicenter study was carried out in 39 patients with active ulcerative colitis (CAI6-8) despite continuous use of steroids (a minimum total dose of 400 mg prednisone within the last 4 wk).Patients received a total of five aphereses using a granulocyte adsorptive technique (Adacolumn(R), Otsuka Pharmaceutical Europe, UK). Assessments at wk 6 and during follow-up until 4 mo comprised clinical (CAI) and endoscopic (EI) activity index, histology, quality of life(IBDQ), and laboratory tests.RESULTS: Thirty-five out of thirty-nine patients were qualified for intent-to-treat analysis. After the apheresis treatment at wk 6, 13/35 (37.1%) patients achieved clinical remission and 10/35 (28.6%) patients had endoscopic remission (CAI<4, EI<4). Quality of life (IBDQ) increased significantly (24 points, P<0.01)at wk 6. Apheresis could be performed in all but one patient. Aphereses were well tolerated, only one patient experienced anemia.CONCLUSION: In patients with steroid refractory ulcerative colitis, five aphereses with a granulocyte/monocyte depleting filter show potential short-term efficacy. Tolerability and technical feasibility of the procedure are excellent.

  6. Safety, Tolerability, and Preliminary Efficacy of the Anti-Fibrotic Small Molecule PRI-724, a CBP/β-Catenin Inhibitor, in Patients with Hepatitis C Virus-related Cirrhosis: A Single-Center, Open-Label, Dose Escalation Phase 1 Trial.

    Science.gov (United States)

    Kimura, Kiminori; Ikoma, Akemi; Shibakawa, Maki; Shimoda, Shinji; Harada, Kenichi; Saio, Masanao; Imamura, Jun; Osawa, Yosuke; Kimura, Masamichi; Nishikawa, Koji; Okusaka, Takuji; Morita, Satoshi; Inoue, Kazuaki; Kanto, Tatsuya; Todaka, Koji; Nakanishi, Yoichi; Kohara, Michinori; Mizokami, Masashi

    2017-08-19

    There is currently no anti-fibrotic drug therapy available to treat hepatitis C virus (HCV) cirrhosis. The aim of this study was to assess the safety, tolerability, and anti-fibrotic effect of PRI-724, a small-molecule modulator of Wnt signaling, in patients with HCV cirrhosis. In this single-center, open-label, phase 1 trial, we sequentially enrolled patients with HCV cirrhosis who were classified as Child-Pugh (CP) class A or B. PRI-724 was administered as a continuous intravenous infusion of 10, 40, or 160mg/m(2)/day for six cycles of 1week on and 1week off. The primary endpoints were frequency and severity of adverse events. The secondary endpoint was efficacy of PRI-724 in treating cirrhosis based on CP score and liver biopsy. This study is registered with ClinicalTrials.gov (no. NCT02195440). Between Sept 3, 2014 and May 2, 2016, 14 patients were enrolled: CP class A:B, 6:8; median age, 62 (range: 43 to 74) years; male:female, 10:4. Twelve of the 14 patients completed six cycles of treatment; one was withdrawn from the study due to possible study drug-related liver injury (grade 3) in the 160mg/m(2)/day dose cohort and one withdrew for personal reasons. Serious adverse events occurred in three patients [21% (3/14)], one of which was possibly related to PRI-724. The most common adverse events were nausea [29% (4/14)] and fatigue [21% (3/14)]. After PRI-724 administration, the CP scores worsened by 1 point in two patients in the 10mg/m(2)/day cohort, improved in three patients at 1, 1, and 2 points in the 40mg/m(2)/day cohort, and improved in one patient by 3 points in the 160mg/m(2)/day cohort. The histology activity index scores of the liver tissue improved in two patients and exacerbated in two patients in the 10mg/m(2)/day cohort, and improved in one patient in the 40mg/m(2)/day cohort. This study showed that administration of 10 or 40mg/m(2)/day intravenous PRI-724 over 12weeks was well-tolerated by patients with HCV cirrhosis; however, liver injury as a

  7. Telmisartan and Insulin Resistance in HIV (TAILoR): protocol for a dose-ranging phase II randomised open-labelled trial of telmisartan as a strategy for the reduction of insulin resistance in HIV-positive individuals on combination antiretroviral therapy.

    Science.gov (United States)

    Pushpakom, Sudeep P; Taylor, Claire; Kolamunnage-Dona, Ruwanthi; Spowart, Catherine; Vora, Jiten; García-Fiñana, Marta; Kemp, Graham J; Whitehead, John; Jaki, Thomas; Khoo, Saye; Williamson, Paula; Pirmohamed, Munir

    2015-10-15

    Telmisartan, an angiotensin receptor blocker, has beneficial effects on insulin resistance and cardiovascular health in non-HIV populations. This trial will evaluate whether telmisartan can reduce insulin resistance in HIV-positive individuals on combination antiretroviral therapy. This is a phase II, multicentre, randomised, open-labelled, dose-ranging trial of telmisartan in 336 HIV-positive individuals over a period of 48 weeks. The trial will use an adaptive design to inform the optimal dose of telmisartan. Patients will be randomised initially 1:1:1:1 to receive one of the three doses of telmisartan (20, 40 and 80 mg) or no intervention (control). An interim analysis will be performed when half of the planned maximum of 336 patients have been followed up for at least 24 weeks. The second stage of the study will depend on the results of interim analysis. The primary outcome measure is a reduction in insulin resistance (as measured by Homeostatic Model Assessment-Insulin Resistance (HOMA-IR)) in telmisartan treated arm(s) after 24 weeks of treatment in comparison with the non-intervention arm. The secondary outcome measures include changes in lipid profile; body fat redistribution (as measured by MRI); plasma and urinary levels of various biomarkers of cardiometabolic and renal health at 12, 24 and 48 weeks. Serious adverse events will be compared between different telmisartan treated dose arm(s) and the control arm. The study, this protocol and related documents have been approved by the National Research Ethics Service Committee North West-Liverpool Central (Ref: 12/NW/0214). On successful completion, study data will be shared with academic collaborators. The findings from TAILoR will be disseminated through peer-reviewed publications, at scientific conferences, the media and through patient and public involvement. 04196/0024/001-0001; 2012-000935-18; 51069819. Published by the BMJ Publishing Group Limited. For permission to use (where not already

  8. A pivotal registration phase III, multicenter, randomized tuberculosis controlled trial: design issues and lessons learnt from the Gatifloxacin for TB (OFLOTUB project

    Directory of Open Access Journals (Sweden)

    Merle Corinne SC

    2012-05-01

    Full Text Available Abstract Background There have been no major advances in tuberculosis (TB drug development since the first East African/British Medical Research Council short course chemotherapy trial 35 years ago. Since then, the landscape for conducting TB clinical trials has profoundly changed with the emergence of HIV infection, the spread of resistant TB bacilli strains, recent advances in mycobacteriological capacity, and drug discovery. As a consequence questions have arisen on the most appropriate approach to design and conduct current TB trials. To highlight key issues discussed: Is a superiority, equivalence, or non-inferiority design most appropriate? What should be the primary efficacy outcome? How to consider re-infections in the definition of the outcome? What is the optimal length of patient follow-up? Is blinding appropriate when treatment duration in test arm is shorter? What are the appropriate assumptions for sample size calculation? Methods Various drugs are currently in the development pipeline. We are presenting in this paper the design of the most recently completed phase III TB trial, the OFLOTUB project, which is the pivotal trial of a registration portfolio for a gatifloxacin-containing TB regimen. It is a randomized, open-label, multicenter, controlled trial aiming to evaluate the efficacy and safety of a gatifloxacin-containing 4-month regimen (trial registration: ClinicalTrial.gov database: NCT00216385. Results In the light of the recent scientific and regulatory discussions, we discuss some of the design issues in TB clinical trials and more specifically the reasons that guided our choices, in order to best answer the trial objectives, while at the same time satisfying regulatory authority requirements. Conclusion When shortening TB treatment, we are advocating for a non-inferiority, non-blinded design, with a composite unfavorable endpoint assessed 12 months post treatment completion, and added trial procedures specifically

  9. Duloxetine in the treatment of major depressive disorder: an open-label study

    Directory of Open Access Journals (Sweden)

    Wang Fujun

    2007-08-01

    Full Text Available Abstract Background Major depressive disorder (MDD is a chronic and highly disabling condition. Existing pharmacotherapies produce full remission in only 30% to 40% of treated patients. Antidepressants exhibiting dual reuptake inhibition of both serotonin (5-HT and norepinephrine (NE may achieve higher rates of remission compared with those acting upon a single neurotransmitter. In this study, the safety and efficacy of duloxetine, a potent dual reuptake inhibitor of 5-HT and NE, were examined. Methods Patients (N = 533 meeting DSM-IV criteria for MDD received open-label duloxetine (60 mg once a day [QD] for 12 weeks during the initial phase of a relapse prevention trial. Patients were required to have a 17-item Hamilton Rating Scale for Depression (HAMD17 total score ≥18 and a Clinical Global Impression of Severity (CGI-S score ≥4 at baseline. Efficacy measures included the HAMD17 total score, HAMD17 subscales, the CGI-S, the Patient Global Impression of Improvement (PGI-I scale, Visual Analog Scales (VAS for pain, and the Symptom Questionnaire, Somatic Subscale (SQ-SS. Quality of life was assessed using the Sheehan Disability Scale (SDS and the Quality of Life in Depression Scale (QLDS. Safety was evaluated by recording spontaneously-reported treatment-emergent adverse events, changes in vital signs and laboratory analytes, and the Patient Global Impression of Sexual Function (PGI-SF scale. Results The rate of discontinuation due to adverse events was 11.3%. Treatment-emergent adverse events reported by ≥10% duloxetine-treated patients were nausea, headache, dry mouth, somnolence, insomnia, and dizziness. Following 12 weeks of open-label duloxetine therapy, significant improvements were observed in all assessed efficacy and quality of life measures. In assessments of depression severity (HAMD17, CGI-S the magnitude of symptom improvement continued to increase at each study visit, while for painful physical symptoms the onset of

  10. Open-label escitalopram treatment for pathological skin picking.

    Science.gov (United States)

    Keuthen, Nancy J; Jameson, Mariko; Loh, Rebecca; Deckersbach, Thilo; Wilhelm, Sabine; Dougherty, Darin D

    2007-09-01

    Pathological skin picking is characterized by dysfunctional, repetitive and excessive manipulation of the skin resulting in noticeable tissue damage. This study sought to assess the effectiveness of escitalopram in treating pathological skin picking. Twenty-nine individuals with pathological skin picking were enrolled in an 18-week, open-label trial of escitalopram. Study measures assessing skin picking severity and impact, anxiety, depression, and quality of life were given at baseline and weeks 2, 4, 6, 10, 14, and 18. The mean maximally tolerated dose was 25.0 mg (standard deviation=8.4). For the 19 study completers, pre-post-treatment analyses revealed significant improvements (Ppicking severity and impact, quality of life, and self-rated anxiety and depression. Completer as well as intent-to-treat analyses indicated that approximately half of the sample satisfied full medication response criteria and one-quarter were partial medication responders. Correlational analyses indicated that changes in depression, anxiety, and quality of life co-occurred with reductions in skin picking severity but not impact. A high percentage of variance in severity, however, remained unexplained. These results suggest that escitalopram can be an effective agent in reducing pathological skin picking. The lack of medication response in a subset of our sample suggests the possibility of pathological skin picking subtypes.

  11. Inhaled low-dose iloprost for pulmonary hypertension: a prospective, multicenter, open-label study.

    Science.gov (United States)

    Sun, Yun-Juan; Xiong, Chang-Ming; Shan, Guang-Liang; Gu, Qing; Zeng, Wei-Jie; Lu, Xian-Ling; Zhu, Feng; Liu, Zhi-Hong; Ni, Xin-Hai; He, Jian-Guo

    2012-06-01

    Inhaled iloprost (average >30 µg/d) has been considered an effective treatment for severe pulmonary hypertension (PH). Further evidence also showed that low-dose iloprost given intravenously was equally effective as high-dose iloprost in the therapy of systemic sclerosis. Patients with pulmonary hypertension will benefit from inhalation of low-dose iloprost. Sixty-two patients with PH were enrolled and initiated with neubulizedlow-dose iloprost (2.5 µg per inhalation, 6× daily) for 24 weeks in 13 medical centers in China. Efficacy endpoints included changes in 6-minute walk distance (6MWD), World Health Organization functional class (WHO-FC), and hemodynamic parameters. Fourteen patients (22.6%) prematurely discontinued the study: 8 due to clinical worsening (6 in WHO-FCIII-IV at baseline), 4 because of protocol change, and 2 patients lost during follow-up. In the remaining 48 patients, 6MWD was increased from 356 ± 98 meters to 414 ± 99 meters (P iloprost inhalation significantly improved exercise capacity and functional status in patients with PH. It was well tolerated. The improvement of hemodynamics was confirmed in patients with WHO-FCI-II but not in patients with WHO-FCIII-IV, suggesting the importance of early treatment in patients with advanced disease stages. © 2012 Wiley Periodicals, Inc.

  12. Open-label, multicenter study of self-administered icatibant for attacks of hereditary angioedema

    DEFF Research Database (Denmark)

    Aberer, W; Maurer, M; Reshef, A

    2014-01-01

    Historically, treatment for hereditary angioedema (HAE) attacks has been administered by healthcare professionals (HCPs). Patient self-administration could reduce delays between symptom onset and treatment, and attack burden. The primary objective was to assess the safety of self...

  13. Adjunctive corticosteroid therapy for Pneumocystis carinii pneumonia in AIDS: a randomized European multicenter open label study

    DEFF Research Database (Denmark)

    Nielsen, T L; Eeftinck Schattenkerk, J K; Jensen, B N

    1992-01-01

    ) survival to discharge, (b) need for mechanical ventilation, and (c) survival at day 90. CS was given within 24 h of standard therapy as intravenous methylprednisolone 2 mg/kg body weight daily for 10 days. All patients received cotrimoxazole as standard treatment. Inclusion criteria were a PaO2 less than 9...

  14. Maintenance therapy with vinflunine plus best supportive care versus best supportive care alone in patients with advanced urothelial carcinoma with a response after first-line chemotherapy (MAJA; SOGUG 2011/02): a multicentre, randomised, controlled, open-label, phase 2 trial.

    Science.gov (United States)

    García-Donas, Jesus; Font, Albert; Pérez-Valderrama, Begoña; Virizuela, José Antonio; Climent, Miquel Ángel; Hernando-Polo, Susana; Arranz, José Ángel; Del Mar Llorente, Maria; Lainez, Nuria; Villa-Guzmán, José Carlos; Mellado, Begoña; Del Alba, Aránzazu González; Castellano, Daniel; Gallardo, Enrique; Anido, Urbano; Del Muro, Xavier García; Domènech, Montserrat; Puente, Javier; Morales-Barrera, Rafael; Pérez-Gracia, Jose Luis; Bellmunt, Joaquim

    2017-05-01

    Maintenance therapy improves outcomes in various tumour types, but cumulative toxic effects limit the choice of drugs. We investigated whether maintenance therapy with vinflunine would delay disease progression in patients with advanced urothelial carcinoma who had achieved disease control with first-line chemotherapy. We did a randomised, controlled, open-label, phase 2 trial in 21 Spanish hospitals. Eligible patients had locally advanced, surgically unresectable, or metastatic transitional-cell carcinoma of the urothelial tract, adequate organ function, and disease control after four to six cycles of cisplatin and gemcitabine (carboplatin allowed after cycle four). Patients were randomly assigned (1:1) to receive vinflunine or best supportive care until disease progression. We initially used block randomisation with a block size of six. Four lists were created for the two stratification factors of starting dose of vinflunine and presence of liver metastases. After a protocol amendment, number of cisplatin and gemcitabine cycles was added as a stratification factor, and eight lists were created, still with a block size of six. Finally, we changed to a minimisation procedure to reduce the risk of imbalance between groups. Vinflunine was given every 21 days as a 20 min intravenous infusion at 320 mg/m(2) or at 280 mg/m(2) in patients with an Eastern Cooperative Oncology Group performance status score of 1, age 75 years or older, previous pelvic radiotherapy, or creatinine clearance lower than 60 mL/min. The primary endpoint was median progression-free survival longer than 5·3 months in the vinflunine group, assessed by modified intention to treat. Comparison of progression-free survival between treatment groups was a secondary endpoint. This trial is registered with ClinicalTrials.gov, number NCT01529411. Between April 12, 2012, and Jan 29, 2015, we enrolled 88 patients, of whom 45 were assigned to receive vinflunine and 43 to receive best supportive care. One

  15. Tocotrienol Treatment in Familial Dysautonomia: Open-Label Pilot Study.

    Science.gov (United States)

    Cheishvili, David; Maayan, Channa; Holzer, Naama; Tsenter, Jeanna; Lax, Elad; Petropoulos, Sophie; Razin, Aharon

    2016-07-01

    Familial dysautonomia (FD) is an autosomal recessive congenital neuropathy, primarily presented in Ashkenazi Jews. The most common mutation in FD patients results from a single base pair substitution of an intronic splice site in the IKBKAP gene which disrupts normal mRNA splicing and leads to tissue-specific reduction of IKBKAP protein (IKAP). To date, treatment of FD patients remains preventative, symptomatic and supportive. Based on previous in vitro evidence that tocotrienols, members of the vitamin E family, upregulate transcription of the IKBKAP gene, we aimed to investigate whether a similar effects was observed in vivo. In the current study, we assessed the effects of tocotrienol treatment on FD patients' symptoms and IKBKAP expression in white blood cells. The initial daily doses of 50 or 100 mg tocotrienol, doubled after 3 months, was administered to 32 FD patients. Twenty-eight FD patients completed the 6-month study. The first 3 months of tocotrienol treatment was associated with a significant increase in IKBKAP expression level in FD patients' blood. Despite doubling the dose after the initial 3 months of treatment, IKBKAP expression level returned to baseline by the end of the 6-month treatment. Clinical improvement was noted in the reported clinical questionnaire (with regard to dizziness, bloching, sweating, number of pneumonia, cough episodes, and walking stability), however, no significant effect was observed in any clinical measurements (weight, height, oxygen saturation, blood pressure, tear production, histamine test, vibration threshold test, nerve conduction, and heart rate variability) following Tocotrienol treatment. In conclusion, tocotrienol treatment appears significantly beneficial by clinical evaluation for some FD patients in a few clinical parameters; however it was not significant by clinical measurements. This open-label study shows the complexity of effect of tocotrienol treatment on FD patients' clinical outcomes and on

  16. Endosonographic radial tumor thickness after neoadjuvant chemoradiation therapy to predict response and survival in patients with locally advanced esophageal cancer: a prospective multicenter phase ll study by the Swiss Group for Clinical Cancer Research (SAKK 75/02).

    Science.gov (United States)

    Jost, Christian; Binek, Janek; Schuller, Jan C; Bauerfeind, Peter; Metzger, Urs; Werth, Baseli; Knuchel, Juerg; Frossard, Jean-Louis; Bertschinger, Philipp; Brauchli, Peter; Meyenberger, Christa; Ruhstaller, Thomas

    2010-06-01

    EUS response assessment in patients with locally advanced esophageal cancer undergoing neoadjuvant chemoradiation therapy (CRT) is limited by disintegration of the involved anatomic structures. Predictive and prognostic values of a prospectively defined maximum tumor thickness (MTT). Prospective open-label phase ll study (SAKK 75/02). Multicenter, nationwide. Of 66 patients with primary CRT, 56 underwent en bloc esophagectomy. EUS-measured MTT before and 2-5 weeks after CRT (yMTT). Cutoffs: (1) absolute thickness (yMTT) after CRT < or = 6 mm; (2) relative reduction compared with baseline (ratio yMTT/MTT) < or = 50%. Correlation between EUS measurements and histopathologic tumor regression grade (TRG) and overall survival (OS). Sixteen of 56 patients were not included for EUS evaluation (10 severe stenosis, 5 MTT not measured, 1 intolerance to second EUS). Characteristics (n = 40) were as follow: median age, 60 years; squamous cell carcinoma, 42%; and adenocarcinoma (AC), 58%. Initial stage was: 10 T2N1, 3 T3N0, 26 T3N1, 1 T3Nx; 14 of 23 AC Siewert type 1. Wilcoxon rank sum test showed significant correlation of TRG1 with yMTT < or = 6 mm (P = .008) and yMTT/MTT < or = 50% (P = .003). The effect of yMTT on TRG1 was significant (P = .0193; odds ratio, 0.687 [95% CI, 0.502-0.941]). The predefined cutoff of < or = 6 mm for yMTT was predictive for TRG1 (P = .0037; Fisher exact test). After a median follow-up of 28.6 months, there was a clear trend for benefit in OS with yMTT < or = 6 mm and yMTT/MTT < or = 50%. Small sample size. In a multicenter setting, MTT measured by EUS after CRT was highly predictive for response and showed a clear trend for predicting survival. Copyright 2010 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

  17. Supervised exercise therapy versus usual care for patellofemoral pain syndrome : an open label randomised controlled trial

    NARCIS (Netherlands)

    van Linschoten, R.; van Middelkoop, M.; Berger, M. Y.; Heintjes, E. M.; Verhaar, J. A. N.; Willemsen, S. P.; Koes, B. W.; Bierma-Zeinstra, S. M.

    2009-01-01

    Objective To assess the effectiveness of supervised exercise therapy compared with usual care with respect to recovery, pain, and function in patients with patellofemoral pain syndrome. Design Open label randomised controlled trial. Setting General practice and sport physician practice. Participants

  18. Supervised exercise therapy versus usual care for patellofemoral pain syndrome : an open label randomised controlled trial

    NARCIS (Netherlands)

    van Linschoten, R.; van Middelkoop, M.; Berger, M. Y.; Heintjes, E. M.; Verhaar, J. A. N.; Willemsen, S. P.; Koes, B. W.; Bierma-Zeinstra, S. M.

    2009-01-01

    Objective To assess the effectiveness of supervised exercise therapy compared with usual care with respect to recovery, pain, and function in patients with patellofemoral pain syndrome. Design Open label randomised controlled trial. Setting General practice and sport physician practice. Participants

  19. Safety of long-term use of linezolid: results of an open-label study

    Directory of Open Access Journals (Sweden)

    Vazquez JA

    2016-09-01

    Full Text Available Jose A Vazquez,1 Anthony C Arnold,2 Robert N Swanson,3 Pinaki Biswas,3 Matteo Bassetti4 1Section of Infectious Diseases, Medical College of Georgia, Georgia Regents University, Augusta, GA, USA; 2UCLA Department of Ophthalmology, Jules Stein Eye Institute, Los Angeles, CA, USA; 3Clinical Research, Global Innovative Pharmaceutical, Pfizer Inc., New York, NY, USA; 4Infectious Diseases Division, Santa Maria della Misericordia University Hospital, Udine, Italy Objective: The objective of this study was to assess the long-term safety of linezolid in patients with chronic infections requiring treatment for ≥6 weeks. Enhanced monitoring for optic neuropathy was included to characterize the early development of this side effect and to identify ophthalmologic tests that might be valuable in early detection of this event. Methods: This was a multicenter, open-label, pilot study of patients aged ≥18 years on long-term linezolid therapy. Matched control patients were included for baseline assessment comparison. Patients were assessed at study entry, monthly while on treatment, at the end of treatment, and 30 days following the last dose. Aggregate ocular safety data were reviewed. Response to treatment was reported. Results: The study was terminated owing to slow enrollment. Twenty-four patients received linezolid; nine patients were included as matched controls. Linezolid was prescribed for a median of 80.5 days (range, 50–254 days. In patients with a reported clinical outcome, the majority were considered improved or cured. Common treatment-related adverse events (AEs included anemia, peripheral neuropathy, polyneuropathy, vomiting, and asthenia, and were consistent with the known safety profile. Most AEs resolved or stabilized with discontinuation of treatment. Results of ophthalmologic tests in the one case adjudicated as probable linezolid-associated optic neuropathy revealed abnormal color vision, characteristic changes in the optic disk

  20. Pregabalin augmentation of antidepressants in older patients with comorbid depression and generalized anxiety disorder-an open-label study.

    Science.gov (United States)

    Karaiskos, Dimitrios; Pappa, Dimitra; Tzavellas, Elias; Siarkos, Kostas; Katirtzoglou, Everina; Papadimitriou, George N; Politis, Antonios

    2013-01-01

    The objective of this 12-week open-label study was to evaluate the efficacy, safety, and tolerability of pregabalin as an adjunctive treatment to antidepressants in older patients suffering from depression and comorbid generalized anxiety disorder (GAD). The initial sample of this open-label study consisted of 94 older patients fulfilling criteria for depression with comorbid GAD who were treated with antidepressants. Twenty of them who had received antidepressant monotherapy for an adequate time and shown partial response to the antidepressant prescribed, in terms of either anxiety or depressive symptomatology, followed the next phase. During the 12-week study period, pregabalin was gradually added to the previously prescribed antidepressant, reaching 225 mg/day over 4 weeks. Depression and anxiety scores as well as side effects were monitored. Within groups, differences of depression and anxiety scores at baseline and during the following 12 weeks of treatment were estimated with repeated-measure analysis of variance. A statistical significant reduction in depression scores was observed after the 4th week of treatment (p anxiety scores, a statistically significant improvement was noted between the 2nd and 4th weeks (p anxiety and depressive symptomatology significantly improved, and minimal side effects were observed. Copyright © 2012 John Wiley & Sons, Ltd.

  1. Long-term safety and efficacy of linagliptin as monotherapy or in combination with other oral glucose-lowering agents in 2121 subjects with type 2 diabetes: up to 2 years exposure in 24-week phase III trials followed by a 78-week open-label extension.

    Science.gov (United States)

    Gomis, R; Owens, D R; Taskinen, M-R; Del Prato, S; Patel, S; Pivovarova, A; Schlosser, A; Woerle, H-J

    2012-08-01

    Aim:  The aim of this study was to evaluate the long-term safety, tolerability and efficacy of the dipeptidyl peptidase-4 inhibitor linagliptin given either alone or in combination with other oral glucose-lowering agents in persons with type 2 diabetes. Methods:  A 78-week open-label extension study evaluated subjects who participated in one of four preceding 24-week, randomised, double-blind, placebo-controlled parent trials and who received linagliptin, linagliptin + metformin, linagliptin + metformin + a sulphonylurea or linagliptin + pioglitazone (all with linagliptin administered orally once daily). Individuals receiving one of these treatments during a previous trial continued the same treatment (n = 1532) for up to a total of 102 weeks, whereas those previously receiving placebo were switched to linagliptin (n = 589). All 2121 participants received at least one dose of the trial medication and were included in the primary safety analysis. Results:  In subjects previously receiving active treatment, the glycosylated haemoglobin A(1c) reduction achieved during the 24-week parent trials was sustained through the 78-week extension period (change from baseline to week 102: -0.8%). Drug-related adverse events were experienced by 14.3% of participants. Hypoglycaemia occurred in 13.9% of participants and was similar between those previously receiving treatment (13.6%) and those switching from placebo to linagliptin (14.6%). Hypoglycaemia occurred most frequently with the use of metformin + a sulphonylurea background therapy (11%). Overall, no clinically relevant changes in body weight were observed. Conclusion:  Long-term treatment with linagliptin was well tolerated with no change in the safety profile observed during the extension study. Sustained long-term glycaemic control was maintained for up to 102 weeks with either linagliptin monotherapy or linagliptin in combination with other oral glucose-lowering agents. © 2012

  2. Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma

    OpenAIRE

    San Miguel, Jesus F.; Weisel, Katja C.; Song, Kevin W.; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Moreau, Philippe; Banos, Anne; Oriol, Albert; Garderet, Laurent; Cavo, Michele; Ivanova, Valentina; Alegre, Adrian; Martinez-Lopez, Joaquin; Chen, Christine

    2015-01-01

    Pomalidomide is a distinct oral IMiD® immunomodulatory agent with direct antimyeloma, stromal-support inhibitory, and immunomodulatory effects. The pivotal, multicenter, open-label, randomized phase 3 trial MM-003 compared pomalidomide + low-dose dexamethasone vs high-dose dexamethasone in 455 patients with refractory or relapsed and refractory multiple myeloma after failure of bortezomib and lenalidomide treatment. Initial results demonstrated significantly longer progression-free survival a...

  3. An open-label clinical trial to investigate the efficacy and safety of corifollitropin alfa combined with hCG in adult men with hypogonadotropic hypogonadism.

    Science.gov (United States)

    Nieschlag, Eberhard; Bouloux, Pierre-Marc G; Stegmann, Barbara J; Shankar, R Ravi; Guan, Yanfen; Tzontcheva, Anjela; McCrary Sisk, Christine; Behre, Hermann M

    2017-03-07

    Hypogonadotropic hypogonadism (HH) in men results in insufficient testicular function and deficiencies in testosterone and spermatogenesis. Combinations of human chorionic gonadotropin (hCG) and recombinant follicle-stimulating hormone (recFSH) have been successful in the treatment of HH. Corifollitropin alfa is a long-acting FSH-analog with demonstrated action in women seeking infertility care. The aim of this study was to investigate the efficacy and safety of corifollitropin alfa combined with hCG to increase testicular volume and induce spermatogenesis in men with HH. This was a Phase III, multi-center, open-label, single-arm trial of corifollitropin alfa in azoospermic men aged 18 to 50 years with HH. After 16 weeks of pretreatment of 23 subjects with hCG alone, 18 subjects with normalized testosterone (T) levels who remained azoospermic entered the 52-week combined treatment phase with hCG twice-weekly and 150 μg corifollitropin alfa every other week. The increase in testicular volume (primary efficacy endpoint) and induction of spermatogenesis resulting in a sperm count ≥1 × 10(6)/mL (key secondary efficacy endpoint) during 52 weeks of combined treatment were assessed. Safety was evaluated by the presence of anti-corifollitropin alfa antibodies and the occurrence of adverse events (AEs). Mean (±SD) testicular volume increased from 8.6 (±6.09) mL to 17.8 (±8.93) mL (geometric mean fold increase, 2.30 [95% CI: 2.03, 2.62]); 14 (77.8%) subjects reached a sperm count ≥1 × 10(6)/mL. No subject developed confirmed anti-corifollitropin alfa antibodies during the trial. Treatment was generally well tolerated. Corifollitropin alfa 150 μg administrated every other week combined with twice-weekly hCG for 52 weeks increased testicular volume significantly, and induced spermatogenesis in >75% of men with HH who had remained azoospermic after hCG treatment alone. ClinicalTrials.gov: NCT01709331 .

  4. A phase 2/3 multicenter randomized clinical trial of ABX-CBL versus ATG as secondary therapy for steroid-resistant acute graft-versus-host disease.

    Science.gov (United States)

    Macmillan, Margaret L; Couriel, Daniel; Weisdorf, Daniel J; Schwab, Gisela; Havrilla, Nancy; Fleming, Thomas R; Huang, Saling; Roskos, Lorin; Slavin, Shimon; Shadduck, Richard K; Dipersio, John; Territo, Mary; Pavletic, Steve; Linker, Charles; Heslop, Helen E; Deeg, H Joachim; Blazar, Bruce R

    2007-03-15

    Treatment for steroid-resistant acute graft-versus-host disease (GVHD) has had limited success. ABX-CBL is a hybridoma-generated murine IgM monoclonal antibody against the CD147 antigen, weakly expressed on human leukocytes and up-regulated on activated lymphocytes. A prospective, multicenter, open-label, randomized clinical trial comparing ABX-CBL to antithymocyte globulin (ATG) for treatment of steroid-resistant acute GVHD was conducted in 95 patients at 21 centers. Forty-eight patients received ABX-CBL daily for 14 consecutive days followed by up to 6 weeks of ABX-CBL twice weekly. Forty-seven patients received equine ATG, 30 mg/kg every other day for a total of 6 doses with additional courses as needed. By day 180, overall improvement was similar in the patients receiving ABX-CBL and in those receiving ATG (56% versus 57%, P = .91). Patient survival at 18 months was less favorable on ABX-CBL than on ATG (35% versus 45%), with the 95% confidence interval ruling out that ABX-CBL provides at least a 10.4% improvement. Data from this trial suggest that ABX-CBL does not offer an improvement over ATG in the treatment of acute steroid-resistant GVHD. This prospective, multicenter, randomized clinical trial for steroid-resistant acute GVHD serves as a model for future evaluation of new agents.

  5. Oral propranolol therapy for infantile hemangiomas beyond the proliferation phase: a multicenter retrospective study.

    Science.gov (United States)

    Zvulunov, Alex; McCuaig, Catherine; Frieden, Ilona J; Mancini, Anthony J; Puttgen, Kate B; Dohil, Magdalene; Fischer, Gayle; Powell, Julie; Cohen, Bernard; Ben Amitai, Dan

    2011-01-01

    Pharmacological therapies for infantile hemangiomas were considered effective only during the proliferative phases. Recently reported beneficial effects of propranolol may extend beyond the proliferative phase of infantile hemangiomas. The purpose of the study was to assess the effect of oral propranolol therapy for infantile hemangiomas beyond the proliferative phase of these lesions. Members of the Society for Pediatric Dermatology were invited to participate in a multicenter retrospective study. Only children with infantile hemangiomas with documented cessation of lesions' growth or those older than 12 months of age were eligible for the study. Clinical and demographic information and digital photographs before, at the start, and following the treatment were collected. Scaled panels of photographs were distributed among preselected experienced pediatric dermatologists. Visual analog scale was used to assess photographs for each case. Paired t-test was used for statistical analyses. Data on 49 eligible patients from eight pediatric dermatology centers was collected. Seven cases were excluded because of insufficient photographic documentation. The age of the patients at the start of propranolol therapy ranged 7 to 120 months (mean 28 mos, median 22 mos). The duration of propranolol therapy ranged 1 to 8 months (mean 3.6 mos). The mean visual analog scale score before the treatment was 6.8 ± 2.15, and mean reduction in the visual analog scale score at the assessment was 2.6 ± 1.74 (p < 0.001). The rate of visual analog scale reduction was 0.4 per month before the start of the therapy, while this rate was accelerated to 0.9 per months following the therapy (p < 0.001). No significant side effects were reported. We conclude that propranolol is effective in infantile hemangiomas, including post-proliferative phase, and should be considered as the first-line therapy in that setting.

  6. Randomized, open-label study to evaluate patient-reported outcomes with fingolimod after changing from prior disease-modifying therapy for relapsing multiple sclerosis: EPOC study rationale and design.

    Science.gov (United States)

    Cascione, Mark; Wynn, Daniel; Barbato, Luigi M; Pestreich, Linda; Schofield, Lesley; McCague, Kevin

    2013-07-01

    The study to Evaluate Patient OutComes, Safety, and Tolerability of Fingolimod (EPOC; NCT01216072) aimed to test the hypothesis that therapy change to oral Gilenya (Novartis AG, Stein, Switzerland) (fingolimod) improves patient-reported outcomes compared with standard-of-care disease-modifying therapy (DMT) in patients with relapsing multiple sclerosis; safety and tolerability were also assessed. This communication describes the study rationale and design. EPOC is a phase 4, open-label, multi-center study conducted in the US and Canada of patients with relapsing forms of multiple sclerosis who are candidates for therapy change. Therapy change eligibility was determined by the treating physician (US patients) or required an inadequate response to or poor tolerance for at least 1 MS therapy (Canadian patients). Patients were randomly assigned in a 3:1 ratio to 6 months of treatment with once-daily oral fingolimod 0.5 mg or standard-of-care DMTs. The primary study end-point was the change from baseline in treatment satisfaction as determined by the global satisfaction sub-scale of the Treatment Satisfaction Questionnaire for Medication. Secondary end-points included changes from baseline in perceived effectiveness and side-effects, and measures of activities of daily living, fatigue, depression, and quality-of-life. A 3-month open-label fingolimod extension was available for patients randomly assigned to the DMT group who successfully completed all study visits. Enrollment has been completed with 1053 patients; the patient population is generally older and has a longer duration of disease compared with populations from phase 3 studies of fingolimod. Inclusion criteria selected for patients with a sub-optimal experience with a previous DMT, limiting the collection of data on therapy change in patients who were satisfied with their previous DMT. Results of the EPOC study are anticipated in early 2013 and will inform treatment selection by providing patient

  7. A Multicenter Phase II Study of Erlotinib and Sorafenib in Chemotherapy-Naive Patients with Advanced Non-Small Cell Lung Cancer

    NARCIS (Netherlands)

    Lind, Joline S. W.; Dingemans, Anne-Marie C.; Groen, Harry J. M.; Thunnissen, Frederik B.; Bekers, Otto; Heideman, Danielle A. M.; Honeywell, Richard J.; Giovannetti, Elisa; Peters, Godefridus J.; Postmus, Pieter E.; van Suylen, Robert Jan; Smit, Egbert F.

    2010-01-01

    Purpose: This multicenter, phase II study evaluates the efficacy and safety of erlotinib, an epidermal growth factor receptor (EGFR) inhibitor, plus sorafenib, a multityrosine kinase inhibitor against vascular endothelial growth factor receptors, in patients with previously untreated advanced

  8. Open-label treatment with desvenlafaxine in postmenopausal women with major depressive disorder not responding to acute treatment with desvenlafaxine or escitalopram.

    Science.gov (United States)

    Soares, Claudio N; Thase, Michael E; Clayton, Anita; Guico-Pabia, Christine J; Focht, Kristen; Jiang, Qin; Kornstein, Susan G; Ninan, Phillip T; Kane, Cecelia P

    2011-03-01

    Preliminary clinical evidence indicates that menopausal status might impact on the efficacy of certain classes of antidepressants. The aim of this study was to evaluate open-label desvenlafaxine treatment (administered as desvenlafaxine succinate) in postmenopausal women who did not achieve clinical response to acute, double-blind treatment with desvenlafaxine or escitalopram. This phase IIIb, multicentre study included a 6-month open-label extension phase of patients who did not respond in the initial 8-week, randomized, double-blind acute phase. Postmenopausal women aged 40-70 years with a primary diagnosis of major depressive disorder were recruited. PRIMARY INTERVENTION: Non-responders to acute treatment with double-blind desvenlafaxine or escitalopram received flexible-dose, open-label desvenlafaxine 100-200 mg/day for the 6-month extension phase. The primary efficacy assessment was the 17-item Hamilton Rating Scale for Depression (HAM-D(17)) total score. Secondary efficacy outcome measures were the Clinical Global Impressions-Improvement (CGI-I) and -Severity scales, Hamilton Rating Scale for Anxiety, Quick Inventory of Depressive Symptomatology-Self-Report, Visual Analogue Scale-Pain Intensity and the Montgomery-Åsberg Depression Rating Scale (MADRS). Secondary health assessments were the Changes in Sexual Functioning Questionnaire, 5-Dimension EuroQoL Index, Health State Today, Menopause Rating Scale, Sheehan Disability Scale, treatment response (≥ 50% decrease in total HAM-D(17) and MADRS score from acute-phase baseline and CGI-I total score ≤ 2), HAM-D(17) remission (total score ≤ 7) and safety. Descriptive statistics were used to summarize outcomes. The efficacy analysis included 123 patients (desvenlafaxine/desvenlafaxine = 64; escitalopram/desvenlafaxine = 59). At final evaluation of the open-label extension phase, mean reductions from acute-phase baseline in HAM-D(17) total scores were -11.33 for the desvenlafaxine

  9. Open-label study of olanzapine in children with pervasive developmental disorder.

    NARCIS (Netherlands)

    Kemner, C.; Swinkels, S.H.N.; Jonge, M.J.A. de; Tuynman-Qua, H.G.; Engeland, H.M. van

    2002-01-01

    The effects of olanzapine on the symptomatology of children with pervasive developmental disorder with emphasis on problems of communication and the safety of the drug were investigated in a 3-month open-label, open-dosage study. Participating in the study were 25 children age 6 to 16 years with a d

  10. An Open-Label Trial of Escitalopram in Pervasive Developmental Disorders.

    Science.gov (United States)

    Owley, Thomas; Walton, Laura; Salt, Jeff; Guter, Stephen J., Jr.; Winnega, Marrea; Leventhal, Bennett L.; Cook, Edwin H., Jr.

    2005-01-01

    Objective: To assess the effect of escitalopram in the treatment of pervasive developmental disorders (PDDs). Method: This 10-week study had a forced titration, open-label design. Twenty-eight subjects (mean age 125.1 [+ or -] 33.5 months) with a PDD received escitalopram at a dose that increased weekly to a maximum dose of 20 mg as tolerated. The…

  11. Open-Label Trial of Atomoxetine Hydrochloride in Adults with ADHD

    Science.gov (United States)

    Johnson, Mats; Cederlund, Mats; Rastam, Maria; Areskoug, Bjorn; Gillberg, Christopher

    2010-01-01

    Background: While atomoxetine is an established treatment for attention-deficit/hyperactivity disorder in children, few studies have examined its efficacy for adults. Methods: Open-label trial of atomoxetine in 20 individuals with ADHD, aged 19-47 years, for 10 weeks, and a total of one year for responders. Results: Ten patients met primary…

  12. Methylphenidate Transdermal System in Adults with Past Stimulant Misuse: An Open-Label Trial

    Science.gov (United States)

    McRae-Clark, Aimee L.; Brady, Kathleen T.; Hartwell, Karen J.; White, Kathleen; Carter, Rickey E.

    2011-01-01

    Objective: This 8-week, open-label trial assessed the efficacy of methylphenidate transdermal system (MTS) in 14 adult individuals diagnosed with ADHD and with a history of stimulant misuse, abuse, or dependence. Method: The primary efficacy endpoint was the Wender-Reimherr Adult ADHD Scale (WRAADS), and secondary efficacy endpoints included the…

  13. Supervised exercise therapy versus usual care for patellofemoral pain syndrome: an open label randomised controlled trial.

    NARCIS (Netherlands)

    R. van Linschoten (Robbart); M. van Middelkoop (Marienke); M.Y. Berger (Marjolein); E.M. Heintjes (Edith); J.A.N. Verhaar (Jan); S.P. Willemsen (Sten); B.W. Koes (Bart); S.M. Bierma-Zeinstra (Sita)

    2009-01-01

    textabstractOBJECTIVE: To assess the effectiveness of supervised exercise therapy compared with usual care with respect to recovery, pain, and function in patients with patellofemoral pain syndrome. DESIGN: Open label randomised controlled trial. SETTING: General practice and sport physician practic

  14. A randomized open-label comparison of the impact of olanzapine versus risperidone on sexual functioning

    NARCIS (Netherlands)

    Knegtering, H; Boks, M; Blijd, C; Castelein, S; Van den Bosch, RJ; Wiersma, D

    2006-01-01

    The objective of this study was to compare sexual functioning in patients treated with olanzapine or risperidone. This open-label trial included 46 patients randomized to olanzapine (5-15mg/d) or risperidone (1-6mg/d) for 6 weeks. We used sexual dysfunction was assessed by a semistructured interview

  15. Open-label study of olanzapine in children with pervasive developmental disorder.

    NARCIS (Netherlands)

    Kemner, C.; Swinkels, S.H.N.; Jonge, M.J.A. de; Tuynman-Qua, H.G.; Engeland, H.M. van

    2002-01-01

    The effects of olanzapine on the symptomatology of children with pervasive developmental disorder with emphasis on problems of communication and the safety of the drug were investigated in a 3-month open-label, open-dosage study. Participating in the study were 25 children age 6 to 16 years with a

  16. Efficacy and safety of flexibly dosed paliperidone palmitate in Chinese patients with acute schizophrenia: an open-label, single-arm, prospective, interventional study

    Directory of Open Access Journals (Sweden)

    Si TM

    2015-06-01

    Full Text Available Tianmei Si,1 Kerang Zhang,2 Jisheng Tang,3 Maosheng Fang,4 Keqing Li,5 Jianmin Zhuo,6 Yu Feng6 1Peking University Institute of Mental Health, Key Laboratory of Mental Health, Ministry of Health, Beijing, People’s Republic of China; 2Shanxi Medical University First Hospital, Shanxi, People’s Republic of China; 3Mental Health Center of Shandong Province, Shandong, People’s Republic of China; 4Mental Health Center, Tongji Medical College, Huazhong University of Science and Technology, Hubei, People’s Republic of China; 5Mental Health Center of Hebei Province, Hebei, People’s Republic of China; 6Janssen Research and Development, Beijing, People’s Republic of China Abstract: This open-label, single-arm, multicenter, 13-week, prospective study explored the efficacy, safety, and tolerability of paliperidone palmitate (150 milligram equivalents [mg eq] [day 1], 100 mg eq [day 8], both deltoid injections; 75–150 mg eq, deltoid/gluteal injection in Chinese patients with acute schizophrenia (Positive and Negative Syndrome Scale [PANSS] total score ≥70, who previously had unsatisfactory therapeutic effect following oral antipsychotic treatment (without washout period. Primary efficacy endpoint was percentage of patients with ≥30% improvement in the PANSS total score at the end of 13 weeks. Secondary efficacy endpoints included change from baseline to end of week 13 in PANSS total score, PANSS subscale scores, Marder factor scores, Clinical Global Impressions–Severity score, and Personal and Social Performance Scale scores. Overall, 477/610 enrolled patients (full analysis set, 78.2% completed the study (men: 55.1%; women: 44.9%; mean age: 31.5 years. Total, 443/610 (72.6%, full analysis set patients achieved primary endpoint (mean [standard deviation] change from baseline: –30.9 [19.51]. All secondary endpoints demonstrated significant improvement at the end of 13 weeks. One death occurred during this acute phase. The most common (>5

  17. Efficacy and safety of once-monthly injection of paliperidone palmitate in hospitalized Asian patients with acute exacerbated schizophrenia: an open-label, prospective, noncomparative study

    Directory of Open Access Journals (Sweden)

    Li HF

    2015-12-01

    Full Text Available HuaFang Li,1 Ibrahim Turkoz,2 Fan Zhang3 1Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Janssen Research & Development, LLC, Titusville, NJ, USA; 3Xi’an Janssen Pharmaceutical Ltd., Beijing, People’s Republic of China Introduction: This single-group, open-label, prospective, noncomparative, multicenter, Phase IV study explored the efficacy and tolerability of paliperidone palmitate (PP in hospitalized patients with acute exacerbation of schizophrenia.Methods: Asian patients of either sex, between 18 and 65 years of age, diagnosed with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition with acute exacerbations within the previous 4 weeks, were enrolled. Intramuscular PP was initiated at doses of 150 milligram equivalent (mg eq (day 1 and 100 mg eq (day 8, followed by a monthly maintenance dose between 75 mg eq and 150 mg eq (days 36 and 64. Primary efficacy endpoint was the change from baseline in the Positive and Negative Syndrome Scale (PANSS total score (last-observation-carried-forward at week 13.Results: Of the 212 enrolled patients, 152 (71.7% completed the 13-week treatment; withdrawal of consent (24 [11.3%] patients was the most common reason for study discontinuation. Mean (standard deviation PANSS total score from baseline (90.0 [17.41] improved significantly at day 4 (-6.1 [9.27]; 95% confidence interval: -7.38, -4.85; P<0.001 and week 13 endpoint (-23.9 [23.24]; 95% confidence interval: -27.10, -20.78; P<0.001. Similarly, the secondary endpoints (Clinical Global Impression-Severity, Physical and Social Performance, each PANSS subscale, and Marder factor scores improved significantly from baseline to week 13 endpoint (P<0.001 for all. At week 13, 112/210 (53.3% patients had a 40% improvement in the PANSS total score (responder rate, and 133/212 (62.7% patients were ready for hospital discharge. Overall, 139 (65

  18. Diagnostic accuracy of the Eurotest for dementia: a naturalistic, multicenter phase II study

    Directory of Open Access Journals (Sweden)

    Frank Ana

    2006-04-01

    Full Text Available Abstract Background Available screening tests for dementia are of limited usefulness because they are influenced by the patient's culture and educational level. The Eurotest, an instrument based on the knowledge and handling of money, was designed to overcome these limitations. The objective of this study was to evaluate the diagnostic accuracy of the Eurotest in identifying dementia in customary clinical practice. Methods A cross-sectional, multi-center, naturalistic phase II study was conducted. The Eurotest was administered to consecutive patients, older than 60 years, in general neurology clinics. The patients' condition was classified as dementia or no dementia according to DSM-IV diagnostic criteria. We calculated sensitivity (Sn, specificity (Sp and area under the ROC curves (aROC with 95% confidence intervals. The influence of social and educational factors on scores was evaluated with multiple linear regression analysis, and the influence of these factors on diagnostic accuracy was evaluated with logistic regression. Results Sixteen neurologists recruited a total of 516 participants: 101 with dementia, 380 without dementia, and 35 who were excluded. Of the 481 participants who took the Eurotest, 38.7% were totally or functionally illiterate and 45.5% had received no formal education. Mean time needed to administer the test was 8.2+/-2.0 minutes. The best cut-off point was 20/21, with Sn = 0.91 (0.84–0.96, Sp = 0.82 (0.77–0.85, and aROC = 0.93 (0.91–0.95. Neither the scores on the Eurotest nor its diagnostic accuracy were influenced by social or educational factors. Conclusion This naturalistic and pragmatic study shows that the Eurotest is a rapid, simple and useful screening instrument, which is free from educational influences, and has appropriate internal and external validity.

  19. A long-term, open-label safety study of single-entity hydrocodone bitartrate extended release for the treatment of moderate to severe chronic pain

    Directory of Open Access Journals (Sweden)

    Nalamachu S

    2014-11-01

    Full Text Available Srinivas Nalamachu,1,2 Richard L Rauck,3 Martin E Hale,4 Orlando G Florete Jr,5 Cynthia Y Robinson,6 Stephen J Farr,6 1International Clinical Research Institute, Overland Park, KS, USA; 2Kansas University Medical Center, Kansas City, KS, USA; 3Carolinas Pain Institute, Center for Clinical Research, Wake Forest University School of Medicine, Winston-Salem, NC, USA; 4Gold Coast Research, LLC, Weston, FL, USA; 5Institute of Pain Management, Jacksonville, FL, USA; 6Zogenix, Inc., Emeryville, CA, USA Objective: To evaluate the long-term safety, tolerability, and effectiveness of single-entity extended-release hydrocodone in opioid-experienced subjects with moderate to severe chronic pain not receiving adequate pain relief or experiencing intolerable side effects from their current opioid. Methods: This multicenter, open-label study started with a conversion/titration phase (≤6 weeks where subjects (n=638 were converted to individualized doses (range 20–300 mg of extended-release hydrocodone dosed every 12 hours, followed by a 48-week maintenance phase (n=424. The primary objective (safety and tolerability and the secondary objective (long-term efficacy as measured by change in average pain score; 0= no pain, 10= worst imaginable pain were monitored throughout the study. Results: Subjects were treated for a range of chronic pain etiologies, including osteoarthritis, low back pain, and neuropathic and musculoskeletal conditions. The mean hydrocodone equivalent dose at screening was 68.9±62.2 mg/day and increased to 139.5±81.7 mg/day at the start of the maintenance phase. Unlimited dose adjustments were permitted at the investigator's discretion during the maintenance phase, reflecting typical clinical practice. No unexpected safety issues were reported. Common adverse events during the conversion/titration and maintenance phases, respectively, were constipation (11.3% and 12.5%, nausea (10.7% and 9.9%, vomiting (4.1% and 9.7%, and somnolence (7

  20. Safety of Repeated Open-Label Treatment Courses of Intravenous Ofatumumab, a Human Anti-CD20 Monoclonal Antibody, in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Quattrocchi, Emilia; Ostergaard, Mikkel; Taylor, Peter C.

    2016-01-01

    Objectives To investigate the safety of ofatumumab retreatment in rheumatoid arthritis. Methods Patients with active rheumatoid arthritis participating in two phase III trials (OFA110635 and OFA110634) and a phase II extension trial (OFA111752) received individualised open-label ofatumumab...... was 463, 182 and 175 patient-years, respectively. Mean time between courses was 17–47 weeks. Ofatumumab induced a profound depletion of peripheral B-lymphocytes. Retreated patients derived benefit based on improvement in DAS28. Adverse events were reported for 93% (226/243), 91% (134/148) and 76% (70...

  1. 卡泊芬净治疗中国成年人侵袭性念珠菌病和食管念珠菌病的安全性、耐受性及疗效的非对照、多中心、开放性研究%A non-controlled, multicenter open-label study to evaluate the safety, tolerability and efficacy of caspofungin in the treatment of invasive candidiasis and esophageal candidiasis

    Institute of Scientific and Technical Information of China (English)

    林东昉; 王健民; 俞云松; 韩明哲; 沈志祥; 宋诗铎; 张婴元

    2014-01-01

    Objective This study was designed to evaluate the safety ,tolerability and efficacy of intravenous caspofungin for treatment of invasive candidiasis and esophageal candidiasis in Chinese adults .Methods This was a non-controlled ,multicenter ,candidiasis .All the 63 patients were included in the safety set (SS) and the full analysis set (FAS) .In the SS ,19 SAEs occurred in 14 patients .All these SAEs were unrelated to caspofungin .There were 73 caspofungin-related non-serious AEs in 31 patients (49 .2% ) .Five patients (7 .9% ) had both clinical AEs and laboratory abnormalities .Eight patients (12 .7% ) had clinical AEs (mainly rashes) ,and 27 patients (42 .9% ) had laboratory abnormalities ,mainly increases in liver enzymes alanine transaminase and aspartate transaminase and reduction in blood potassium .About 91 .7% of the clinical AEs were mild to moderate .Treatment was discontinued in 1 patient (1 .6% ,1/63) due to AEs .The overall efficacy was 58 .1% (36/62) in the FAS and 70 .0% (35/70) in the per-protocol set (PPS) .In the FAS ,the therapeutic efficacy was 57 .6% (34/59) for invasive candidiasis and 66 .7% (2/3) for esophageal candidiasis .In the PPS , the therapeutic efficacy was 68 .8% (33/48 ) for invasive candidiasis and 100% (3/3 ) for esophageal candidiasis .Conclusions The AEs of caspofungin were mostly mild to moderate in the treatment of invasive candidiasis and esophageal candidiasis in Chinese adults .Only one patient terminated therapy due to drug-related AE .Caspofungin is safe and effective for the treatment of invasive candidiasis and esophageal candidiasis in Chinese adults .%目的:评价卡泊芬净注射剂治疗中国成年人侵袭性念珠菌病和食管念珠菌病的疗效及安全性。方法本研究为非对照、多中心、开放性临床研究,入选对象为年龄≥18岁,确诊为侵袭性念珠菌病或食管念珠菌病需要进行抗真菌治疗的中国成人患者。采用卡泊芬净静脉给药,每日50 mg

  2. Safety and Outcomes of Open-Label Deferasirox Iron Chelation Therapy for Mucormycosis▿

    OpenAIRE

    2009-01-01

    We sought to describe the safety profile of open-label, adjunctive deferasirox iron chelation therapy in eight patients with biopsy-proven mucormycosis. Deferasirox was administered for an average of 14 days (range, 7 to 21) at 5 to 20 mg/kg of body weight/day. The only adverse effects attributable to deferasirox were rashes in two patients. Deferasirox treatment was not associated with changes in renal or liver function, complete blood count, or transplant immunosuppressive levels. Thus, def...

  3. Safety of a new compact catheter for men with neurogenic bladder dysfunction: a randomised, crossover and open-labelled study

    DEFF Research Database (Denmark)

    Chartier-Kastler, E; Lauge, I; Ruffion, A

    2011-01-01

    Self-catheterising males aged ≥18 years with spinal cord lesion and normal/impaired urethral sensation were enrolled in this comparative, randomised, crossover and open-labelled multicentre trial....

  4. Short-term open-label chamomile (Matricaria chamomilla L.) therapy of moderate to severe generalized anxiety disorder.

    Science.gov (United States)

    Keefe, John R; Mao, Jun J; Soeller, Irene; Li, Qing S; Amsterdam, Jay D

    2016-12-15

    Conventional drug treatments for Generalized Anxiety Disorder (GAD) are often accompanied by substantial side effects, dependence, and/or withdrawal syndrome. A prior controlled study of oral chamomile (Matricaria chamomilla L.) extract showed significant efficacy versus placebo, and suggested that chamomile may have anxiolytic activity for individuals with GAD. We hypothesized that treatment with chamomile extract would result in a significant reduction in GAD severity ratings, and would be associated with a favorable adverse event and tolerability profile. We report on the open-label phase of a two-phase randomized controlled trial of chamomile versus placebo for relapse-prevention of recurrent GAD. Subjects with moderate to severe GAD received open-label treatment with pharmaceutical-grade chamomile extract 1500mg/day for up to 8 weeks. Primary outcomes were the frequency of clinical response and change in GAD-7 symptom scores by week 8. Secondary outcomes included the change over time on the Hamilton Rating Scale for Anxiety, the Beck Anxiety Inventory, and the Psychological General Well Being Index. Frequency of treatment-emergent adverse events and premature treatment discontinuation were also examined. Of 179 subjects, 58.1% (95% CI: 50.9% to 65.5%) met criteria for response, while 15.6% prematurely discontinued treatment. Significant improvement over time was also observed on the GAD-7 rating (β=-8.4 [95% CI=-9.1 to -7.7]). A similar proportion of subjects demonstrated statistically significant and clinically meaningful reductions in secondary outcome ratings of anxiety and well-being. Adverse events occurred in 11.7% of subjects, although no serious adverse events occurred. Chamomile extract produced a clinically meaningful reduction in GAD symptoms over 8 weeks, with a response rate comparable to those observed during conventional anxiolytic drug therapy and a favorable adverse event profile. Future comparative effectiveness trials between chamomile and

  5. Safety and Outcomes of Open-Label Deferasirox Iron Chelation Therapy for Mucormycosis▿

    Science.gov (United States)

    Spellberg, Brad; Andes, David; Perez, Mario; Anglim, Anne; Bonilla, Hector; Mathisen, Glenn E.; Walsh, Thomas J.; Ibrahim, Ashraf S.

    2009-01-01

    We sought to describe the safety profile of open-label, adjunctive deferasirox iron chelation therapy in eight patients with biopsy-proven mucormycosis. Deferasirox was administered for an average of 14 days (range, 7 to 21) at 5 to 20 mg/kg of body weight/day. The only adverse effects attributable to deferasirox were rashes in two patients. Deferasirox treatment was not associated with changes in renal or liver function, complete blood count, or transplant immunosuppressive levels. Thus, deferasirox appears safe as an adjunctive therapy for mucormycosis. PMID:19433555

  6. The Japan Statin Treatment Against Recurrent Stroke (J-STARS: A Multicenter, Randomized, Open-label, Parallel-group Study

    Directory of Open Access Journals (Sweden)

    Naohisa Hosomi

    2015-09-01

    Funding: This study was initially supported by a grant from the Ministry of Health, Labour and Welfare, Japan. After the governmental support expired, it was conducted in collaboration between Hiroshima University and the Foundation for Biomedical Research and Innovation.

  7. Symptom and Quality of Life Improvement in LUX-Lung 8, an Open-Label Phase III Study of Second-Line Afatinib Versus Erlotinib in Patients With Advanced Squamous Cell Carcinoma of the Lung After First-Line Platinum-Based Chemotherapy.

    Science.gov (United States)

    Felip, Enriqueta; Hirsh, Vera; Popat, Sanjay; Cobo, Manuel; Fülöp, Andrea; Dayen, Charles; Trigo, José M; Gregg, Richard; Waller, Cornelius F; Soria, Jean-Charles; Goss, Glenwood D; Gordon, James; Wang, Bushi; Palmer, Michael; Ehrnrooth, Eva; Gadgeel, Shirish M

    2017-06-23

    In the phase III LUX-Lung 8 trial, afatinib significantly improved progression-free survival (PFS) and overall survival (OS) versus erlotinib in patients with squamous cell carcinoma (SCC) of the lung progressing during or after platinum-based chemotherapy. Patient-reported outcomes (PROs) and health-related quality of life (QoL) in these patients are presented. Patients (n = 795) were randomized 1:1 to oral afatinib (40 mg/d) or erlotinib (150 mg/d). PROs were collected (baseline, every 28 days until progression, 28 days after discontinuation) using the European Organization for Research and Treatment of Cancer QoL questionnaire and lung cancer-specific module. The percentage of patients improved during therapy, time to deterioration (TTD), and changes over time were analyzed for prespecified lung cancer-related symptoms and global health status (GHS)/QoL. Questionnaire compliance was 77.3% to 99.0% and 68.7% to 99.0% with afatinib and erlotinib, respectively. Significantly more patients who received afatinib versus erlotinib experienced improved scores for GHS/QoL (36% vs. 28%; P = .041) and cough (43% vs. 35%; P = .029). Afatinib significantly delayed TTD in dyspnea (P = .008) versus erlotinib, but not cough (P = .256) or pain (P = .869). Changes in mean scores favored afatinib for cough (P = .0022), dyspnea (P = .0007), pain (P = .0224), GHS/QoL (P = .0320), and all functional scales. Differences in adverse events between afatinib and erlotinib, specifically diarrhea, did not affect GHS/QoL. In patients with SCC of the lung, second-line afatinib was associated with improved prespecified disease-related symptoms and GHS/QoL versus erlotinib, complementing PFS and OS benefits with afatinib. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Efficacy and Safety of First-Line Necitumumab Plus Gemcitabine and Cisplatin Versus Gemcitabine and Cisplatin In East Asian Patients with Stage IV Squamous Non-Small Cell Lung Cancer: A Subgroup Analysis of the Phase 3, Open-Label, Randomized SQUIRE Study.

    Science.gov (United States)

    Park, Keunchil; Cho, Eun Kyung; Bello, Maximino; Ahn, Myung-Ju; Thongprasert, Sumitra; Song, Eun-Kee; Soldatenkova, Victoria; Depenbrock, Henrik; Puri, Tarun; Orlando, Mauro

    2017-01-06

    The phase 3 randomized SQUIRE study revealed significantly longer overall survival (OS) and progression-free survival (PFS) for necitumumab plus gemcitabine and cisplatin (neci+GC) than for gemcitabine and cisplatin alone (GC) in 1093 patients with previously untreated advanced squamous non-small cell lung cancer (NSCLC). This post hoc subgroup analysis assessed the efficacy and safety of neci+GC among East Asian (EA) patients enrolled in the study. All patients received up to six 3-week cycles of gemcitabine (Days 1, 8; 1250 mg/m²) and cisplatin (Day 1; 75 mg/m²). Patients in the neci+GC arm also received necitumumab (Days 1, 8; 800 mg) until disease progression or unacceptable toxicity. Hazard ratios (HRs) and 95% CIs were estimated from stratified Cox proportional hazards models. In EA patients, there were improvements for neci+GC (n=43) vs GC (n=41) in OS (HR: 0.805, 95% CI: 0.484-1.341) and PFS (HR: 0.720, 95% CI: 0.439-1.180), consistent with the results for non-EA patients observed in the present study. The overall safety data were consistent between EA and non-EA patients. A numerically higher proportion of patients experienced serious adverse events (AEs), Grade ≥3 AEs, and AEs with an outcome of death for (i) neci+GC vs GC in EA patients and (ii) EA patients vs non-EA patients for neci+GC. Although limited by the small sample size and post hoc nature of the analysis, these findings are consistent with those of the overall study and suggest that neci+GC offers a survival advantage and favorable benefit/risk for EA patients with advanced squamous NSCLC.

  9. Adjunctive rufinamide in Lennox-Gastaut syndrome: a long-term, open-label extension study.

    Science.gov (United States)

    Kluger, G; Glauser, T; Krauss, G; Seeruthun, R; Perdomo, C; Arroyo, S

    2010-09-01

    This open-label extension evaluated the long-term efficacy and tolerability of rufinamide in patients with Lennox-Gastaut syndrome (LGS) who had previously completed a 12-week double-blind study. In total, 124 patients (aged 4-37 years), receiving 1-3 concomitant antiepileptic drugs, were treated with rufinamide approximately 25-60 mg/kg/day. Efficacy was assessed by seizure frequency; tolerability by adverse events (AEs) and laboratory tests. Overall, patients were treated with rufinamide for a median (range) of 432 (10-1149) days. Reductions in seizure frequency were observed throughout the study; during the last 12 months of treatment, 41.0% and 47.9% of patients had > or = 50% reduction in total and tonic-atonic seizure frequency, respectively. The most common AEs were vomiting (30.6%) and pyrexia (25.8%). In this open-label extension, rufinamide appeared to be an effective long-term adjunctive therapy for the treatment of LGS-associated seizures in children and young adults.

  10. Long-term safety and efficacy of clobazam for Lennox-Gastaut syndrome: interim results of an open-label extension study.

    Science.gov (United States)

    Ng, Yu-Tze; Conry, Joan; Paolicchi, Juliann; Kernitsky, Lydia; Mitchell, Wendy; Drummond, Rebecca; Isojarvi, Jouko; Lee, Deborah; Owen, Randall

    2012-12-01

    In an ongoing open-label extension (OV-1004), patients with Lennox-Gastaut syndrome who had completed 1 of 2 randomized controlled trials (OV-1002 [Phase II] or OV-1012 [Phase III]) are receiving clobazam at dosages ≤2.0 mg/kg/day (≤80 mg/day). Of 306 eligible patients from OV-1002 or OV-1012, 267 entered the open-label extension. As of the interim date, July 1, 2010, 213 patients (79.8%) had remained in the trial, and 189 had received clobazam for ≥12 months, 128 for ≥18 months, and 94 for ≥24 months. Median percentage decreases in average weekly rates of drop seizures were 71.1% and 91.6% at Months 3 and 24. Mean modal and mean maximum daily dosages were 0.94 mg/kg and 1.22 mg/kg for those who had received clobazam for ≥1 year. The 4 most common adverse events were upper respiratory tract infection (18.4%), fall (14.2%), pneumonia (13.9%), and somnolence (12.7%). Clobazam's adverse event profile was consistent with its profile in controlled trials.

  11. Antidepressant monotherapy compared with combinations of antidepressants in the treatment of resistant depressive patients: a randomized, open-label study.

    Science.gov (United States)

    Bares, Martin; Novak, Tomas; Kopecek, Miloslav; Stopkova, Pavla; Cermak, Jan; Kozeny, Jiri; Höschl, Cyril

    2013-02-01

    This randomized, 6-week, open-label study compared efficacy of CAD and antidepressant monotherapies (ADM) that had been chosen according to clinical judgment of the attending psychiatrist. A total of 60 inpatients (intent-to-treat analysis) with depressive disorder (≥ 1 unsuccessful antidepressant treatment) were randomly assigned to the interventions. The responders who completed the acute phase of study, were evaluated for relapse within 2 months of follow-up treatment. The primary outcome measure was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) and response was defined as a ≥ 50% reduction of MADRS score. Mean changes in total MADRS score from baseline to week 6 for patients in both treatment modalities were not different (ADM = 13.2 ± 8.6 points; CAD = 14.5 ± 9.5 points; P = 0.58). The analysis of covariance performed for significantly higher value of imipramine equivalent dose in CAD group showed only a non-significant between-group difference for total MADRS change (P = 0.17). There were also no differences between groups in response rate (ADM = 48%; CAD = 58%) and number of drop-outs in acute treatment as well as proportion of responders' relapses in the follow-up. Both treatment modalities produced clinically relevant reduction of depressive symptomatology in acute treatment of patients with resistant depression and their effect was comparable.

  12. Clinical trial of nintedanib in patients with recurrent or metastatic salivary gland cancer of the head and neck: A multicenter phase 2 study (Korean Cancer Study Group HN14-01).

    Science.gov (United States)

    Kim, Youjin; Lee, Su Jin; Lee, Ji Yun; Lee, Se-Hoon; Sun, Jong-Mu; Park, Keunchil; An, Ho Jung; Cho, Jae Yong; Kang, Eun Joo; Lee, Ha-Young; Kim, Jinsoo; Keam, Bhumsuk; Kim, Hye Ryun; Lee, Kyoung Eun; Choi, Moon Young; Lee, Ki Hyeong; Ahn, Myung-Ju

    2017-06-01

    Salivary gland cancers (SGCs) are uncommon and account for less than 5% of all head and neck cancers, but they are histologically heterogeneous. No specific therapy, including targeted agents, has consistently improved clinical outcomes in recurrent/metastatic SGC. Recent studies suggest that vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) play important roles in SGC. Nintedanib is a potent small-molecule, triple-receptor tyrosine kinase inhibitor (VEGFR1, VEGFR2, and VEGFR3; fibroblast growth factor receptor 1 [FGFR1], FGFR2, and FGFR3; and PDGFRα and PDGFRß). This study sought to determine the antitumor activity of nintedanib in patients with recurrent or metastatic SGC. This open-label, multicenter, phase 2, single-arm study was conducted at 11 hospitals in South Korea. Patients with pathologically confirmed recurrent and/or metastatic SGC for whom at least 1 line of systemic chemotherapy had failed were enrolled. Nintedanib was given orally at 200 mg twice a day until disease progression or unacceptable toxicity. The primary endpoint was the response rate. The secondary endpoints were progression-free survival, overall survival, toxicity, and the disease-control rate. The Simon 2-stage minimax design was used. The median age of the patients was 54 years, 60% were female, and 95% had an Eastern Cooperative Oncology Group performance status of 0 or 1. The majority of the patients had adenoid cystic carcinoma (65%), and 40% received at least 2 prior rounds of chemotherapy. After 20 patients were enrolled, the study was stopped because no responders were observed at stage I. There were no partial responses, but the disease-control rate was 75% (15 of 20). The median duration of stable disease was 8.2 months (range, 1.76-12.36 months). At the time of the data cutoff, with a median follow-up of 9.5 months, the median overall survival had not been reached, and the progression-free survival rate at 6 months was

  13. [Long-term opioid therapy in chronic noncancer pain. A systematic review and meta-analysis of efficacy, tolerability and safety in open-label extension trials with study duration of at least 26 weeks].

    Science.gov (United States)

    Häuser, W; Bernardy, K; Maier, C

    2015-02-01

    aberrant drug behavior by independent expert assessment. There was no significant change (p = 0.50) in pain intensity between the end of the randomized period and the end of open-label phase (SMD 0.19 [- 0.03, 0.41]; six studies with 1360 participants). Only a minority of patients selected for opioid therapy at randomization finished the long-term open-label study. However, sustained effects of pain reduction could be demonstrated in these patients. LtOT can be considered in carefully selected and monitored CNCP patients who experience clinically meaningful pain reduction with at least tolerable AE in short-term opioid therapy. The English full-text version of this article is freely available at SpringerLink (under "Supplementary Material").

  14. Improvement of hemodialysis catheter function with tenecteplase: a phase III, open-label study: TROPICS 4.

    Science.gov (United States)

    Fishbane, Steven; Milligan, Samuel L; Lempert, Kenneth D; Hertel, Joachim E W; Wetmore, James B; Oliver, Matthew J; Blaney, Martha; Gillespie, Barbara S; Jacobs, Joan R; Begelman, Susan M

    2011-01-01

    Hemodialysis (HD) catheters are prone to thrombotic occlusion. We evaluated tenecteplase, a thrombolytic, for the treatment of dysfunctional HD catheters. Patients with tunneled HD catheters and blood flow rate (BFR) tenecteplase (2 mg/lumen) for a 1 h intracatheter dwell. Treatment success was defined as BFR ≥ 300 mL/min and a ≥ 25 mL/min increase from baseline BFR, 30 min before and at the end of HD. Patients without treatment success at the end of the initial visit received another 2 mg dose of tenecteplase for an up to 72 h extended dwell. Of 223 enrolled patients, 34% (95% confidence interval [CI], 28-40%) had treatment success after a 1 h dwell. Mean (standard deviation [SD]) BFR change from baseline was 82 (124) mL/min. Treatment success in those who received extended-dwell tenecteplase (n = 116) was 49% (95% CI, 40-58%), with mean (SD) BFR change from baseline of 117 (140) mL/min. Reported targeted adverse events included five catheter-related bloodstream infections and one thrombosis. No intracranial hemorrhage, major bleeding, embolic events, or catheter-related complications were reported. Tenecteplase administered as a 1 h or 1 h plus extended dwell was associated with improved HD catheter function in the TROPICS 4 trial.

  15. Phase II open-label study of nintedanib in patients with recurrent glioblastoma multiforme

    DEFF Research Database (Denmark)

    Muhic, Aida; Poulsen, Hans Skovgaard; Mau-Sørensen, Paul Morten;

    2013-01-01

    glioblastoma multiforme (GBM) who had previously failed radiotherapy plus temozolomide as first-line therapy (STUPP), or the same regimen with subsequent bevacizumab-based therapy as second-line treatment (BEV). Patients with a performance status of 0-1, histologically proven GBM, and measurable disease (by...

  16. Phase III Randomized Study of Bendamustine Compared With Chlorambucil in Previously Untreated Patients With Chronic Lymphocytic Leukemia

    National Research Council Canada - National Science Library

    Wolfgang U. Knauf; Toshko Lissichkov; Ali Aldaoud; Anna Liberati; Javier Loscertales; Raoul Herbrecht; Gunnar Juliusson; Gerhard Postner; Liana Gercheva; Stefan Goranov; Martin Becker; Hans-Joerg Fricke; Francoise Huguet; Ilaria Del Giudice; Peter Klein; Lothar Tremmel; Karlheinz Merkle; Marco Montillo

    2009-01-01

    This randomized, open-label, parallel-group, multicenter study was designed to compare the efficacy and safety of bendamustine and chlorambucil in previously untreated patients with advanced (Binet stage B or C...

  17. A randomized, open-label pilot comparison of gabapentin and bupropion SR for smoking cessation.

    Science.gov (United States)

    White, William D; Crockford, David; Patten, Scott; El-Guebaly, Nady

    2005-10-01

    This 6-week, randomized, open-label pilot study estimated the treatment effect size of gabapentin (n = 17) compared with bupropion SR (n = 19) for smoking cessation, thereby allowing sample size calculations for a definitive comparison study. The primary outcome measure was smoking cessation. Secondary outcome measures included smoking reduction and withdrawal severity. Gabapentin was less efficacious than bupropion for smoking cessation but was associated with fewer dropouts from adverse effects. Withdrawal severity was less with bupropion. Bupropion remains the first-line non-nicotine pharmacotherapy for smoking cessation. Further study is required to determine if gabapentin has any useful role in smoking cessation. Based on our primary outcome measure, 79 subjects would be required in each treatment group of a two-armed study to achieve 90% power for detecting a difference in efficacy between gabapentin and bupropion.

  18. An open-label pilot study of infliximab therapy in diffuse cutaneous systemic sclerosis

    DEFF Research Database (Denmark)

    Denton, C P; Engelhart, M; Tvede, N

    2008-01-01

    AIM: The safety and potential efficacy of a chimaeric anti-tumour necrosis factor alpha monoclonal antibody (infliximab) were examined in diffuse cutaneous systemic sclerosis (dcSSc). METHODS: A 26-week open-label pilot study in which 16 cases of dcSSc received five infusions of infliximab (5 mg...... of type I collagen by dermal fibroblasts was reduced at 26 weeks compared with baseline (p = 0.02). There were no deaths during the study and no suspected unexpected serious adverse reactions. 21 serious adverse events (AE) occurred in seven subjects, mostly attributable to dcSSc. 127 distinct AE occurred...... in 16 subjects. Of these, 19 AE (15%) were probably or definitely related to infliximab treatment. Eight (50%) patients prematurely discontinued infliximab. Anti-infliximab antibodies developed during the study in five subjects and were significantly associated with suspected infusion reactions (p = 0...

  19. Open-label placebo treatment in chronic low back pain: a randomized controlled trial

    Science.gov (United States)

    Carvalho, Cláudia; Caetano, Joaquim Machado; Cunha, Lidia; Rebouta, Paula; Kaptchuk, Ted J.; Kirsch, Irving

    2016-01-01

    Abstract This randomized controlled trial was performed to investigate whether placebo effects in chronic low back pain could be harnessed ethically by adding open-label placebo (OLP) treatment to treatment as usual (TAU) for 3 weeks. Pain severity was assessed on three 0- to 10-point Numeric Rating Scales, scoring maximum pain, minimum pain, and usual pain, and a composite, primary outcome, total pain score. Our other primary outcome was back-related dysfunction, assessed on the Roland–Morris Disability Questionnaire. In an exploratory follow-up, participants on TAU received placebo pills for 3 additional weeks. We randomized 97 adults reporting persistent low back pain for more than 3 months' duration and diagnosed by a board-certified pain specialist. Eighty-three adults completed the trial. Compared to TAU, OLP elicited greater pain reduction on each of the three 0- to 10-point Numeric Rating Scales and on the 0- to 10-point composite pain scale (P < 0.001), with moderate to large effect sizes. Pain reduction on the composite Numeric Rating Scales was 1.5 (95% confidence interval: 1.0-2.0) in the OLP group and 0.2 (−0.3 to 0.8) in the TAU group. Open-label placebo treatment also reduced disability compared to TAU (P < 0.001), with a large effect size. Improvement in disability scores was 2.9 (1.7-4.0) in the OLP group and 0.0 (−1.1 to 1.2) in the TAU group. After being switched to OLP, the TAU group showed significant reductions in both pain (1.5, 0.8-2.3) and disability (3.4, 2.2-4.5). Our findings suggest that OLP pills presented in a positive context may be helpful in chronic low back pain. PMID:27755279

  20. Are open-Label Placebos Ethical? Informed Consent and Ethical Equivocations.

    Science.gov (United States)

    Blease, Charlotte; Colloca, Luana; Kaptchuk, Ted J

    2016-07-01

    The doctor-patient relationship is built on an implicit covenant of trust, yet it was not until the post-World War Two era that respect for patient autonomy emerged as an article of mainstream medical ethics. Unlike their medical forebears, physicians today are expected to furnish patients with adequate information about diagnoses, prognoses and treatments. Against these dicta there has been ongoing debate over whether placebos pose a threat to patient autonomy. A key premise underlying medical ethics discussion is the notion that the placebo effect necessitates patient deception. Indeed, the American Medical Association guidelines imply that placebo treatment necessary entails a form of deception. As a consequence of this assumption, the fulcrum of debate on the use of placebo treatment has hinged on whether that deception is ever justified. Recently performed experiments with open-label transparently prescribed placebos have begun to challenge the notion that deception is necessary in eliciting the placebo effect and such effects necessarily involve a binary distinction between autonomy and beneficence. In this article we focus on the content of disclosures in distinctive open-label, transparently disclosed placebo studies and inquire whether they might be said to invoke deception in clinical contexts, and if so, whether the deception is unethical. We find that open placebos may be said to involve equivocation over how placebos work. However, drawing on surveys of patient attitudes we suggest that this equivocation appears to be acceptable to patients. We conclude that open placebos fulfil current American Medical Association guidelines for placebo use, and propose future research directions for harnessing the placebo effect ethically.

  1. A prospective open-label trial of lamotrigine monotherapy in children and adolescents with bipolar disorder.

    Science.gov (United States)

    Biederman, Joseph; Joshi, Gagan; Mick, Eric; Doyle, Robert; Georgiopoulos, Anna; Hammerness, Paul; Kotarski, Meghan; Williams, Courtney; Wozniak, Janet

    2010-04-01

    To evaluate the safety and efficacy of lamotrigine monotherapy as an acute treatment of bipolar mood elevation in children with bipolar spectrum disorders. This was a 12-week, open-label, prospective trial of lamotrigine monotherapy to assess the effectiveness and tolerability of this compound in treating pediatric bipolar disorder. Assessments included the Young Mania Rating Scale (YMRS), Clinical Global Impressions-Improvement scale (CGI-I), Children's Depression Rating Scale (CDRS), and Brief Psychiatric Rating Scale (BPRS). Adverse events were assessed through spontaneous self-reports, vital signs weight monitoring, and laboratory analysis. Thirty-nine children with bipolar disorder (YMRS at entry: 31.6 +/- 5.5) were enrolled in the study and 22 (56%) completed the 12-week trial. Lamotrigine was slowly titrated to an average endpoint dose of 160.7 +/- 128.3 in subjects children 12-17 years of age (N = 17). Treatment with lamotrigine was associated with statistically significant levels of improvement in mean YMRS scores (-14.9 +/- 9.7, P disorder (ADHD), and psychotic symptoms. Lamotrigine was generally well tolerated with marginal increase in body weight (47.0 +/- 18.0 kg vs. 47.2 +/- 17.9 kg, P= 0.6) and was not associated with abnormal changes in laboratory parameters. Several participants were discontinued due to skin rash; in all cases, the rash resolved shortly after discontinuation of treatment. No patient developed Steven Johnson syndrome. Open-label lamotrigine treatment appears to be beneficial in the treatment of bipolar disorder and associated conditions in children. Future placebo-controlled, double-blind studies are warranted to confirm these findings.

  2. Safety and efficacy of aliskiren/amlodipine/hydrochlorothiazide triple combination in patients with moderate to severe hypertension: a 54-week, open-label study.

    Science.gov (United States)

    Murray, Alexander V; Koenig, Wolfgang; Garcia-Puig, Juan; Patel, Samir; Uddin, Alkaz; Zhang, Jack

    2012-12-01

    Combination antihypertensive therapies are recommended to attain blood pressure (BP) targets especially in high-risk patients in whom rapid and pronounced BP control is essential. This 28- to 54-week, open-label, multicenter study evaluated the safety and efficacy of a triple combination, aliskiren with amlodipine and hydrochlorothiazide (HCTZ), in patients with moderate to severe hypertension. Following a washout period of up to 4 weeks, patients received aliskiren/HCTZ 300/12.5 mg for 1 week, followed by add-on amlodipine 5 mg for 1 week. Thereafter, the doses of amlodipine and HCTZ were doubled. The first 206 of 564 patients who completed 28 weeks of study continued for an additional 26 weeks. Safety was assessed by recording all adverse events. Efficacy variables included changes in BP from baseline to endpoint and BP control rate. Of 564 patients, 493 completed the study. Peripheral edema (9.4%), headache (5.7%), nasopharyngitis (4.1%), and bronchitis (3.7%) were reported frequently. Clinically significant reductions in mean sitting systolic BP/mean sitting diastolic BP from baseline (-34.2/-20.3 mm Hg and -37.3/-21.8 mm Hg at weeks 28 and 54, respectively) were observed. Corresponding BP control rates were 69.1% and 77.1%. The aliskiren/amlodipine/HCTZ combination in patients with moderate to severe hypertension was well tolerated and provided clinically significant BP reductions and effective BP control. © 2012 Wiley Periodicals, Inc.

  3. Long-term tolerability of tolterodine extended release in children 5-11 years of age: results from a 12-month, open-label study

    DEFF Research Database (Denmark)

    Nijman, Rien J M; Borgstein, Niels G; Ellsworth, Pamela

    2007-01-01

    suggestive of detrusor overactivity (>/=1 diurnal incontinence episode per 24h for >/=5 of 7 d) and >/=6 voids per 24h at baseline and had completed the 12-wk double-blind study. Patients received tolterodine ER (2mg once daily) for 12 mo. The primary end points were the incidence and severity of adverse......OBJECTIVE: To evaluate the long-term tolerability of tolterodine extended release (ER) in children (aged 5-11 yr) with urgency urinary incontinence (UUI). METHODS: This was a multicenter, open-label extension of a 12-wk, double-blind, placebo-controlled study of tolterodine ER. Patients had UUI......-blind tolterodine ER, n=221; placebo, n=97). The majority of patients were white (90%), mean+/-SD age was 7.6+/-1.5 yr, and 54% were boys. Forty-nine percent of patients reported >/=1 AE during the study, similar to that observed in the preceding 12-wk study (42%). The most frequent AEs were urinary tract infection...

  4. Safety of Repeated Open-Label Treatment Courses of Intravenous Ofatumumab, a Human Anti-CD20 Monoclonal Antibody, in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Quattrocchi, Emilia; Ostergaard, Mikkel; Taylor, Peter C.

    2016-01-01

    OBJECTIVES: To investigate the safety of ofatumumab retreatment in rheumatoid arthritis. METHODS: Patients with active rheumatoid arthritis participating in two phase III trials (OFA110635 and OFA110634) and a phase II extension trial (OFA111752) received individualised open-label ofatumumab...... retreatment (700 mg X 2 intravenous infusions two weeks apart) ≥24 weeks following the first course and ≥16 weeks following further courses. Retreatment required evidence of clinical response followed by disease relapse. These studies were prematurely terminated by the sponsor to refocus development...... was 463, 182 and 175 patient-years, respectively. Mean time between courses was 17-47 weeks. Ofatumumab induced a profound depletion of peripheral B-lymphocytes. Retreated patients derived benefit based on improvement in DAS28. Adverse events were reported for 93% (226/243), 91% (134/148) and 76% (70...

  5. Correlation of EGFR-expression with safety and efficacy outcomes in SQUIRE: a randomized, multicenter, open-label, phase III study of gemcitabine–cisplatin plus necitumumab versus gemcitabine–cisplatin alone in the first-line treatment of patients with stage IV squamous non-small-cell lung cancer

    Science.gov (United States)

    Paz-Ares, L.; Socinski, M. A.; Shahidi, J.; Hozak, R. R.; Soldatenkova, V.; Kurek, R.; Varella-Garcia, M.; Thatcher, N.; Hirsch, F. R.

    2016-01-01

    Background SQUIRE demonstrated addition of necitumumab to gemcitabine and cisplatin significantly improved survival in patients with stage IV sq-NSCLC. Here, we report additional outcomes for the subpopulation of patients with tumor epidermal growth factor receptor (EGFR) protein expression. Patients and methods Patients with pathologically confirmed stage IV sq-NSCLC were randomized 1:1 to receive a maximum of six 3-week cycles of gemcitabine (1250 mg/m2 i.v., days 1 and 8) and cisplatin (75 mg/m2 i.v., day 1) chemotherapy with or without necitumumab (800 mg i.v., days 1 and 8). Patients in the chemotherapy plus necitumumab group with no progression continued on necitumumab alone until disease progression or intolerable toxicity. SQUIRE included mandatory tissue collection. EGFR protein expression was detected by immunohistochemistry (IHC) in a central laboratory. Exploratory analyses were pre-specified for patients with EGFR protein expressing (EGFR > 0) and non-expressing (EGFR = 0) tumors. Results A total of 982 patients [90% of intention-to-treat (ITT)] had evaluable IHC results. The large majority of these patients (95%) had tumor samples expressing EGFR protein; only 5% had tumors without detectable EGFR protein. Overall survival (OS) for EGFR > 0 patients was significantly longer in the necitumumab plus gemcitabine–cisplatin group than in the gemcitabine–cisplatin group {stratified hazard ratio (HR) 0.79 [95% confidence interval (CI) 0.69, 0.92; P = 0.002]; median 11.7 months (95% CI 10.7, 12.9) versus 10.0 months (8.9, 11.4)}. Additionally, an OS benefit was seen in all pre-specified subgroups in EGFR > 0 patients. However, OS HR for EGFR = 0 was 1.52. Adverse events of interest with the largest difference between treatment groups in EGFR > 0 patients (Grade ≥3) were hypomagnesemia (10% versus <1%) and skin rash (6% versus <1%). Conclusions In line with SQUIRE ITT, addition of necitumumab to gemcitabine–cisplatin significantly prolonged OS and was generally well tolerated in the subpopulation of patients with EGFR-expressing advanced sq-NSCLC. The benefit from addition of necitumumab to chemotherapy was not apparent in this analysis for the small subgroup of patients with non-EGFR-expressing tumors. Clinical Trial NCT00981058. PMID:27207107

  6. An open-label, multicenter, phase 2a study to assess the feasibility of imaging metastases in late-stage cancer patients with the {alpha}{sub v}{beta}{sub 3}-selective angiogenesis imaging agent {sup 99m}Tc-NC100692

    Energy Technology Data Exchange (ETDEWEB)

    Axelsson, Rimma [Division of Radiology, Dept. of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Inst., Karolinska Univ. Hospital, Stockholm (Sweden)], e-mail: rimma.axelsson@ki.se; Bach-Gansmo, Tore [The Norwegian Radium Hospital, Oslo (Norway); Castell-Conesa, Juan [Hospital Universitari Vall d' Hebron, Barcelona (Spain); McParland, Brian J. [Research and Development, Medical Diagnostics, GE Healthcare Ltd., Amersham (United Kingdom)

    2010-01-15

    Background: The {alpha}{sub v}{beta}{sub 3} integrin is one of the angiogenesis-related membrane proteins highly expressed on the neovasculature of breast cancer and lung carcinomas. Labeling of the {alpha}{sub v}{beta}{sub 3} integrin with {sup 99m}Tc-NC100692 provides a potential tool for imaging angiogenesis and hence the presence of malignant lesions. Purpose: To determine the feasibility of detecting metastatic lesions in liver, lung, bone, and brain with scintigraphy using the {alpha}{sub v}{beta}{sub 3}-avid imaging agent {sup 99m}Tc-NC100692 in patients with breast or lung cancer, and to assess its safety profile. Material and Methods: Twenty-five patients, 15 with lung cancer and 10 with breast cancer, were recruited at 10 centers. Metastases were newly diagnosed by computed tomography, magnetic resonance imaging, or bone scintigraphy, i.e., the reference standard. Patients underwent whole-body scans of approximately 10-15 min duration beginning at 45 min post-injection and a SPECT acquisition of approximately 30 min beginning at 75 min after injection of up to 1100 MBq {sup 99m}Tc-NC100692. In case of liver metastases, dynamic acquisitions of 15 min were performed starting immediately post-injection. Safety measurements were performed up to 2.5 hours after injection and included hematology, serum biochemistry, coagulation, urine analysis, vital signs, oximetry, 12-lead ECG assessments, and a physical examination. Results: In patients with breast cancer, {sup 99m}Tc-NC100692 scintigraphy detected 1 of 7 liver, 4 of 5 lung, 8 of 17 bone, and 1 of 1 brain metastases. The corresponding numbers for lung cancer patients were 0 of 2, 17 of 18, 2 of 2, and 7 of 9. There was overall stability through the follow-up period for all investigated safety parameters. Conclusion: Scintigraphy with {sup 99m}Tc-NC100692 is feasible for detection of lung and brain metastases from breast and lung cancer, while the detection of liver and bone lesions is poor. The use of {sup 99m}Tc-NC100692 is safe and well tolerated.

  7. An open-label, multicenter, phase 2a study to assess the feasibility of imaging metastases in late-stage cancer patients with the alpha{sub v}beta{sub 3}-selective angiogenesis imaging agent 99mTc-NC100692

    Energy Technology Data Exchange (ETDEWEB)

    Axelsson, Rimma (Division of Radiology, Dept. of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Inst., Karolinska Univ. Hospital, Stockholm (Sweden)), e-mail: rimma.axelsson@ki.se; Bach-Gansmo, Tore (The Norwegian Radium Hospital, Oslo (Norway)); Castell-Conesa, Juan (Hospital Universitari Vall d' Hebron, Barcelona (Spain)); McParland, Brian J. (Research and Development, Medical Diagnostics, GE Healthcare Ltd., Amersham (United Kingdom))

    2010-01-15

    Background: The alpha{sub v}beta{sub 3} integrin is one of the angiogenesis-related membrane proteins highly expressed on the neovasculature of breast cancer and lung carcinomas. Labeling of the alpha{sub v}beta{sub 3} integrin with 99mTc-NC100692 provides a potential tool for imaging angiogenesis and hence the presence of malignant lesions. Purpose: To determine the feasibility of detecting metastatic lesions in liver, lung, bone, and brain with scintigraphy using the alpha{sub v}beta{sub 3}-avid imaging agent 99mTc-NC100692 in patients with breast or lung cancer, and to assess its safety profile. Material and Methods: Twenty-five patients, 15 with lung cancer and 10 with breast cancer, were recruited at 10 centers. Metastases were newly diagnosed by computed tomography, magnetic resonance imaging, or bone scintigraphy, i.e., the reference standard. Patients underwent whole-body scans of approximately 10-15 min duration beginning at 45 min post-injection and a SPECT acquisition of approximately 30 min beginning at 75 min after injection of up to 1100 MBq 99mTc-NC100692. In case of liver metastases, dynamic acquisitions of 15 min were performed starting immediately post-injection. Safety measurements were performed up to 2.5 hours after injection and included hematology, serum biochemistry, coagulation, urine analysis, vital signs, oximetry, 12-lead ECG assessments, and a physical examination. Results: In patients with breast cancer, 99mTc-NC100692 scintigraphy detected 1 of 7 liver, 4 of 5 lung, 8 of 17 bone, and 1 of 1 brain metastases. The corresponding numbers for lung cancer patients were 0 of 2, 17 of 18, 2 of 2, and 7 of 9. There was overall stability through the follow-up period for all investigated safety parameters. Conclusion: Scintigraphy with 99mTc-NC100692 is feasible for detection of lung and brain metastases from breast and lung cancer, while the detection of liver and bone lesions is poor. The use of 99mTc-NC100692 is safe and well tolerated

  8. Correlation of EGFR-expression with safety and efficacy outcomes in SQUIRE: a randomized, multicenter, open-label, phase III study of gemcitabine-cisplatin plus necitumumab versus gemcitabine-cisplatin alone in the first-line treatment of patients with stage IV squamous non-small-cell lung cancer.

    Science.gov (United States)

    Paz-Ares, L; Socinski, M A; Shahidi, J; Hozak, R R; Soldatenkova, V; Kurek, R; Varella-Garcia, M; Thatcher, N; Hirsch, F R

    2016-08-01

    SQUIRE demonstrated addition of necitumumab to gemcitabine and cisplatin significantly improved survival in patients with stage IV sq-NSCLC. Here, we report additional outcomes for the subpopulation of patients with tumor epidermal growth factor receptor (EGFR) protein expression. Patients with pathologically confirmed stage IV sq-NSCLC were randomized 1:1 to receive a maximum of six 3-week cycles of gemcitabine (1250 mg/m(2) i.v., days 1 and 8) and cisplatin (75 mg/m(2) i.v., day 1) chemotherapy with or without necitumumab (800 mg i.v., days 1 and 8). Patients in the chemotherapy plus necitumumab group with no progression continued on necitumumab alone until disease progression or intolerable toxicity. SQUIRE included mandatory tissue collection. EGFR protein expression was detected by immunohistochemistry (IHC) in a central laboratory. Exploratory analyses were pre-specified for patients with EGFR protein expressing (EGFR > 0) and non-expressing (EGFR = 0) tumors. A total of 982 patients [90% of intention-to-treat (ITT)] had evaluable IHC results. The large majority of these patients (95%) had tumor samples expressing EGFR protein; only 5% had tumors without detectable EGFR protein. Overall survival (OS) for EGFR > 0 patients was significantly longer in the necitumumab plus gemcitabine-cisplatin group than in the gemcitabine-cisplatin group {stratified hazard ratio (HR) 0.79 [95% confidence interval (CI) 0.69, 0.92; P = 0.002]; median 11.7 months (95% CI 10.7, 12.9) versus 10.0 months (8.9, 11.4)}. Additionally, an OS benefit was seen in all pre-specified subgroups in EGFR > 0 patients. However, OS HR for EGFR = 0 was 1.52. Adverse events of interest with the largest difference between treatment groups in EGFR > 0 patients (Grade ≥3) were hypomagnesemia (10% versus SQUIRE ITT, addition of necitumumab to gemcitabine-cisplatin significantly prolonged OS and was generally well tolerated in the subpopulation of patients with EGFR-expressing advanced sq-NSCLC. The benefit from addition of necitumumab to chemotherapy was not apparent in this analysis for the small subgroup of patients with non-EGFR-expressing tumors. NCT00981058. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

  9. Safety and efficacy of combination therapy of interferon-alpha2 + JAK1-2 Inhibitor in the philadelphia-negative chronic myeloproliferative neoplasms. Preliminary results from the danish combi-trial-an open label, single arm, non-randomized multicenter phase II study

    DEFF Research Database (Denmark)

    Mikkelsen, S. U.; Kjaer, L.; Skov, V.

    2015-01-01

    .4 weeks (range, 3.4 weeks-43.3 weeks). Twenty-seven pts were previously treated with IFNa2 (n=18 intolerant, n=5 unresponsive, n=4 both). Three pts were treatment-naive. Twenty-seven pts (90%) remained on CT; 3 pts discontinued treatment due to an AE. One patient died from transformation to AML shortly......, necessitating pausing medication for > 2 weeks. Eleven SAEs requiring hospitalization were recorded in 9 pts: pneumonia (n=3), fever (n=2), lipotymia, hematemesis, phlebitis, herpes zoster, angina pectoris and arterial hypertension, 1 patient each. Conclusion: CT with IFNa2 and ruxolitinib is highly efficacious...

  10. Safety and efficacy of combination therapy of interferon-alpha2 + JAK1-2 Inhibitor in the philadelphia-negative chronic myeloproliferative neoplasms. Preliminary results from the danish combi-trial-an open label, single arm, non-randomized multicenter phase II study

    DEFF Research Database (Denmark)

    Mikkelsen, S. U.; Kjaer, L.; Skov, V.

    2015-01-01

    Background: The Philadelphia-negative, chronic myeloproliferative neoplasms (MPN) include essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (MF) (PMF). Chronic inflammation and a deregulated immune system are considered important for clonal evolution and disease....... Hct control without phlebotomy was achieved by week 4 in 78 % of pts (7 of 9), who at baseline had an elevated hct. Only 3 pts required a total of 3 phlebotomies after initiation of CT. In Figure 1 median hct levels at 0, 1, 3, 6 months are shown. Overall, complete response (CR) was achieved as best......) or major response (n=2) was achieved in 4 pts (57.1%) by week 2 or 1 month, and NR in 3 pts (42.8%). Among PPV-MF pts, 2 pts (66.7%) achieved CR and 1 patient (33,3%) PR by week 2. Furthermore, JAK2V617F% declined significantly as depicted in Figure 2 (JAK2V617F% over time for each patient) and 3 (median...

  11. Efficacy and Safety of Azithromycin-Chloroquine versus Sulfadoxine-Pyrimethamine for Intermittent Preventive Treatment of Plasmodium falciparum Malaria Infection in Pregnant Women in Africa: An Open-Label, Randomized Trial.

    Directory of Open Access Journals (Sweden)

    Joshua Kimani

    Full Text Available The World Health Organization recommends intermittent preventive treatment in pregnancy (IPTp with sulfadoxine-pyrimethamine (SP in African regions with moderate to high malaria transmission. However, growing resistance to SP threatens the effectiveness of IPTp-SP, and alternative drugs are needed. This study tested the efficacy, tolerability, and safety of a fixed-dose combination azithromycin-chloroquine (AZCQ; 250 mg AZ/155 mg CQ base for IPTp relative to IPTp-SP.A randomized, Phase 3, open-label, multi-center study was conducted in sub-Saharan Africa (Benin, Kenya, Malawi, Tanzania, and Uganda between October 2010 and November 2013. Pregnant women received 3 IPTp courses with AZCQ (each course: 1,000/620 mg AZCQ QD for 3 days or SP (each course 1,500/75 mg SP QD for 1 day at 4- to 8-week intervals during the second and third trimester. Long-lasting insecticide-treated bednets were also provided at enrollment. Study participants were followed up until day 28 post delivery (time window: day 28-42. The primary endpoint was the proportion of participants with sub-optimal pregnancy outcomes (a composite endpoint comprising live-borne neonates with low birth weight [LBW, 28 weeks], abortion [≤28 weeks], lost to follow-up prior to observation of pregnancy outcome, or missing birth weight. The study was terminated early after recruitment of 2,891 of the planned 5,044 participants, due to futility observed in a pre-specified 35% interim analysis. In the final intent-to-treat dataset, 378/1,445 (26.2% participants in the AZCQ and 342/1,445 (23.7% in the SP group had sub-optimal pregnancy outcomes, with an estimated risk ratio (RR of 1.11 (95% CI: 0.97, 1.25; p = 0.12. There was no significant difference in the incidence of LBW between treatment groups (57/1138 [5.0%] in the AZCQ group, 68/1188 [5.7%] in the SP group, RR 0.87 [95% CI: 0.62, 1.23]; p = 0.44. IPTp-AZCQ was less well-tolerated in mothers than IPTp-SP. Occurrences of congenital anomalies

  12. Aquatic therapy versus conventional land-based therapy for Parkinson's disease: an open-label pilot study.

    Science.gov (United States)

    Vivas, Jamile; Arias, Pablo; Cudeiro, Javier

    2011-08-01

    To assess and compare 2 different protocols of physiotherapy (land or water therapy) for people with Parkinson's disease (PD) focused on postural stability and self-movement, and to provide methodological information regarding progression within the program for a future larger trial. Randomized, controlled, open-label pilot trial. Outpatients, Parkinson's disease Center of Ferrol-Galicia (Spain). Individuals (N=11) with idiopathic PD in stages 2 or 3 according to the Hoehn and Yahr Scale completed the investigation (intervention period plus follow-up). After baseline evaluations, participants were randomly assigned to a land-based therapy (active control group) or a water-based therapy (experimental group). Participants underwent individual sessions for 4 weeks, twice a week, for 45 minutes per session. Both interventions were matched in terms of exercise features, which were structured in stages with clear objectives and progression criteria to pass to the next phase. Participants underwent a first baseline assessment, a posttest immediately after 4 weeks of intervention, and a follow-up assessment after 17 days. Evaluations were performed OFF-dose after withholding medication for 12 hours. Functional assessments included the Functional Reach Test (FRT), the Berg Balance Scale (BBS), the UPDRS, the 5-m walk test, and the Timed Up and Go test. A main effect of both therapies was seen for the FRT. Only the aquatic therapy group improved in the BBS and the UPDRS. In this pilot study, physiotherapy protocols produced improvement in postural stability in PD that was significantly larger after aquatic therapy. The intervention protocols are shown to be feasible and seem to be of value in amelioration of postural stability-related impairments in PD. Some of the methodological aspects detailed here can be used to design larger controlled trials. Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  13. Intravenous Immunoglobulin Therapy in Pediatric Narcolepsy: A Nonrandomized, Open-Label, Controlled, Longitudinal Observational Study

    Science.gov (United States)

    Lecendreux, Michel; Berthier, Johanna; Corny, Jennifer; Bourdon, Olivier; Dossier, Claire; Delclaux, Christophe

    2017-01-01

    Study Objectives: Previous case reports of intravenous immunoglobulins (IVIg) in pediatric narcolepsy have shown contradictory results. Methods: This was a nonrandomized, open-label, controlled, longitudinal observational study of IVIg use in pediatric narcolepsy with retrospective data collection from medical files obtained from a single pediatric national reference center for the treatment of narcolepsy in France. Of 56 consecutively referred patients with narcolepsy, 24 received IVIg (3 infusions administered at 1-mo intervals) in addition to standard care (psychostimulants and/or anticataplectic agents), and 32 continued on standard care alone (controls). Results: For two patients in each group, medical files were unavailable. Of the 22 IVIg patients, all had cerebrospinal fluid (CSF) hypocretin ≤ 110 pg/mL and were HLA-DQB1*06:02 positive. Of the 30 control patients, 29 were HLA-DQB1*06:02 positive and of those with available CSF measurements, all 12 had hypocretin ≤ 110 pg/mL. Compared with control patients, IVIg patients had shorter disease duration, shorter latency to sleep onset, and more had received H1N1 vaccination. Mean (standard deviation) follow-up length was 2.4 (1.1) y in the IVIg group and 3.9 (1.7) y in controls. In multivariate-adjusted linear mixed-effects analyses of change from baseline in Ullanlinna Narcolepsy Scale (UNS) scores, high baseline UNS, but not IVIg treatment, was associated with a reduction in narcolepsy symptoms. On time-to-event analysis, among patients with high baseline UNS scores, control patients achieved a UNS score narcolepsy symptoms were not significantly reduced by IVIg. However, in patients with high baseline symptoms, a subset of IVIg-treated patients achieved remission more rapidly than control patients. Commentary: A commentary on this article appears in this issue on page 363. Citation: Lecendreux M, Berthier J, Corny J, Bourdon O, Dossier C, Delclaux C. Intravenous immunoglobulin therapy in pediatric

  14. Six week open-label reboxetine treatment in children and adolescents with attention deficit hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Arabgol F

    2007-10-01

    Full Text Available Background: Attention Deficit Hyperactivity Disorder (ADHD is a common psychiatric disorder among children and adolescents. This disorder causes difficulties in academic, behavioral, emotional, social and family performance. Stimulants show robust efficacy and a good safety profile in children with this disorder, but a significant percent of ADHD children do not respond adequately or cannot tolerate the associated adverse effects with stimulants. Such difficulties highlight the need for alternative safe and effective medications in the treatment of this disorder. This open-label study assessed the effectiveness of reboxetine, a selective norepinephrine reuptake inhibitor, in children and adolescents with attention deficit hyperactivity disorder (ADHD."nMethods: Fifteen child and adolescent outpatients, aged 7 to 16 (Mean± SD=9.72±2.71 years, diagnosed with ADHD were enrolled in a six open-label study with reboxetine 4-6 mg/d. The principal measure of the outcome was the teacher and parent Attention Deficit Hyperactive Disorder Rating Scale (ADHD Rating Scale. Patients were assessed by a child psychiatrist at baseline, 2, 4 and 6 weeks of the medication started. Side effects questionnaire was used to detect side effects of reboxetine. Repeated measures Analysis of variance (ANOVA was done for comparison of Teacher and Parent ADHD Rating Scale scores during the intervention."nResults: Twelve of 15 (80% participants completed the treatment protocol. A significant decrease in ADHD symptoms on teacher (p=0.04 and parent (p=0.003 ADHD rating scale was noted. Adverse effects were mild to moderate in severity. The most common adverse effects were drowsiness/sedation and appetite decrease."nConclusion: The results of the current study suggest the effectiveness of reboxetine in the treatment of ADHD in children and adolescents. Double-blind, placebo-controlled studies and larger sample size with long duration of intervention are indicated to rigorously

  15. Effect of enzyme therapy in juvenile patients with Pompe disease: a three-year open-label study.

    NARCIS (Netherlands)

    Capelle, C.I. van; Beek, N.A. van der; Hagemans, M.L.; Arts, W.F.M.; Hop, W.C.J.; Lee, P.; Jaeken, J.; Frohn-Mulder, I.M.; Merkus, P.J.F.M.; Corzo, D.; Puga, A.C.; Reuser, A.J.J.; Ploeg, A.T. van der

    2010-01-01

    Pompe disease is a rare neuromuscular disorder caused by deficiency of acid alpha-glucosidase. Treatment with recombinant human alpha-glucosidase recently received marketing approval based on prolonged survival of affected infants. The current open-label study was performed to evaluate the response

  16. Open-label trial of anti-TNF-alpha in dermato- and polymyositis treated concomitantly with methotrexate

    DEFF Research Database (Denmark)

    Hengstman, G.J.; Bleecker, J.L. De; Feist, E.

    2008-01-01

    BACKGROUND/AIMS: To determine the efficacy of infliximab combined with weekly methotrexate in drug-naive recent-onset dermatomyositis and polymyositis. METHODS: A multicentre open-label controlled trial was conducted. Disease activity was assessed using patient's and physician's disease activity...

  17. Effect of enzyme therapy in juvenile patients with Pompe disease: a three-year open-label study.

    NARCIS (Netherlands)

    Capelle, C.I. van; Beek, N.A. van der; Hagemans, M.L.; Arts, W.F.M.; Hop, W.C.J.; Lee, P.; Jaeken, J.; Frohn-Mulder, I.M.; Merkus, P.J.F.M.; Corzo, D.; Puga, A.C.; Reuser, A.J.J.; Ploeg, A.T. van der

    2010-01-01

    Pompe disease is a rare neuromuscular disorder caused by deficiency of acid alpha-glucosidase. Treatment with recombinant human alpha-glucosidase recently received marketing approval based on prolonged survival of affected infants. The current open-label study was performed to evaluate the response

  18. An Open-Label Study of Aripiprazole : Pharmacokinetics, Tolerability, and Effectiveness in Children and Adolescents with Conduct Disorder

    NARCIS (Netherlands)

    Findling, Robert L.; Kauffman, Ralph; Sallee, Floyd R.; Salazar, Daniel E.; Sahasrabudhe, Vaishali; Kollia, Georgia; Kornhauser, David M.; Vachharajani, Nimish N.; Assuncao-Talbott, Sheila; Mallikaarjun, Suresh; Iwamoto, Taro; McQuade, Robert D.; Boulton, David W.; Blumer, Jeffrey

    2009-01-01

    Objectives: This study evaluated flexible-dose pharmacokinetics, safety, and effectiveness of aripiprazole in children and adolescents with conduct disorder (CD). Methods: This open-label, 15-day, three-center study with an optional 36-month extension enrolled a total of 23 patients: 12 children (6-

  19. An Open-Label Study of Aripiprazole : Pharmacokinetics, Tolerability, and Effectiveness in Children and Adolescents with Conduct Disorder

    NARCIS (Netherlands)

    Findling, Robert L.; Kauffman, Ralph; Sallee, Floyd R.; Salazar, Daniel E.; Sahasrabudhe, Vaishali; Kollia, Georgia; Kornhauser, David M.; Vachharajani, Nimish N.; Assuncao-Talbott, Sheila; Mallikaarjun, Suresh; Iwamoto, Taro; McQuade, Robert D.; Boulton, David W.; Blumer, Jeffrey

    Objectives: This study evaluated flexible-dose pharmacokinetics, safety, and effectiveness of aripiprazole in children and adolescents with conduct disorder (CD). Methods: This open-label, 15-day, three-center study with an optional 36-month extension enrolled a total of 23 patients: 12 children

  20. Leflunomide treatment in corticosteroid-dependent myasthenia gravis: an open-label pilot study.

    Science.gov (United States)

    Chen, Pei; Feng, Huiyu; Deng, Juan; Luo, Yufei; Qiu, Li; Ou, Changyi; Liu, Weibin

    2016-01-01

    Leflunomide is an effective drug used in the treatment of rheumatoid arthritis. Here we report the findings of an open-label pilot study, which found that leflunomide is also an effective treatment for myasthenia gravis (MG). This study recruited 15 corticosteroid-dependent MG patients. For 6 months, leflunomide 20 mg was given to these patients daily along with prednisone. The quantitative myasthenia gravis (QMG) scores and MG activities of daily living (MG-ADL) profiles were measured in these MG patients. After 6 months of treatment, 9 of the 15 patients enrolled in this study showed improvements in both QMG and MG-ADL. The mean QMG scores (13.4 to 8.5) and MG-ADL profiles (5.8 to 2.8) were significantly decreased (P = 0.01, 0.006 respectively). Furthermore, we found that the mean corticosteroid doses were reduced after treatment with leflunomide (24.3 to 12.3 mg per day). Leflunomide is a well-tolerated and efficacious treatment for corticosteroid-dependent MG, which may also enable lower doses of corticosteroids to be administered.

  1. An Open-Label Trial of Memantine for Cognitive Impairment in Patients with Posttraumatic Stress Disorder

    Directory of Open Access Journals (Sweden)

    Sriram Ramaswamy

    2015-01-01

    Full Text Available Background. Studies using standard neuropsychological instruments have demonstrated memory deficits in patients with PTSD. We evaluated the efficacy and safety of the N-methyl-D-aspartate antagonist memantine in veterans with PTSD and cognitive impairment. Methods. Twenty-six veterans with PTSD and cognitive impairment received 16 weeks of memantine in an open-label fashion. Cognition was assessed using the Spatial Span, Logical Memory I, and Letter-Number Sequencing subtests of the Wechsler Memory Scale III and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS. RBANS measures attention, language, visuospatial skills, and immediate and delayed memories. The Clinician Administered PTSD Scale (CAPS, Hamilton Depression Scale (HAM-D, Hamilton Anxiety Scale (HAM-A, Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q, and Sheehan Disability Scale (SDS were secondary outcome measures. Results. There was a significant improvement in RBANS, both total and subscale scores (P<0.05, over time. There was a reduction in total CAPS scores, avoidance/numbing symptoms (CAPS-C and hyperarousal symptoms (CAPS-D, HAM-D, Q-LES-Q, and SDS scores. However, there was no reduction in reexperiencing (CAPS-B and HAM-A scores. Memantine was well tolerated. Conclusions. Memantine improved cognitive symptoms, PTSD symptoms, and mood in veterans with PTSD. Randomized double-blind studies are needed to validate these preliminary observations.

  2. Open-Label, Randomized Study of Transition From Tacrolimus to Sirolimus Immunosuppression in Renal Allograft Recipients

    Science.gov (United States)

    Tedesco-Silva, Helio; Peddi, V. Ram; Sánchez-Fructuoso, Ana; Marder, Brad A.; Russ, Graeme R.; Diekmann, Fritz; Flynn, Alison; Hahn, Carolyn M.; Li, Huihua; Tortorici, Michael A.; Schulman, Seth L.

    2016-01-01

    Background Calcineurin inhibitor–associated nephrotoxicity and other adverse events have prompted efforts to minimize/eliminate calcineurin inhibitor use in kidney transplant recipients. Methods This open-label, randomized, multinational study evaluated the effect of planned transition from tacrolimus to sirolimus on kidney function in renal allograft recipients. Patients received tacrolimus-based immunosuppression and then were randomized 3 to 5 months posttransplantation to transition to sirolimus or continue tacrolimus. The primary end point was percentage of patients with 5 mL/min per 1.73 m2 or greater improvement in estimated glomerular filtration rate from randomization to month 24. Results The on-therapy population included 195 patients (sirolimus, 86; tacrolimus, 109). No between-group difference was noted in percentage of patients with 5 mL/min per 1.73 m2 or greater estimated glomerular filtration rate improvement (sirolimus, 34%; tacrolimus, 42%; P = 0.239) at month 24. Sirolimus patients had higher rates of biopsy-confirmed acute rejection (8% vs 2%; P = 0.02), treatment discontinuation attributed to adverse events (21% vs 3%; P < 0.001), and lower rates of squamous cell carcinoma of the skin (0% vs 5%; P = 0.012). Conclusions Our findings suggest that renal function improvement at 24 months is similar for patients with early conversion to sirolimus after kidney transplantation versus those remaining on tacrolimus. PMID:27500260

  3. Oral zinc sulfate treatment for viral warts: an open-label study.

    Science.gov (United States)

    Mun, Je-Ho; Kim, Su-Han; Jung, Do-Sang; Ko, Hyun-Chang; Kim, Byung-Soo; Kwon, Kyung-Sool; Kim, Moon-Bum

    2011-06-01

    Viral warts, which are caused by the human papilloma virus, are a common problem in dermatology. Various modalities have been used to treat warts, but none are uniformly effective or directly antiviral. Recent studies show that oral zinc sulfate could be effective in the treatment of viral warts. Thirty-one patients with multiple, non-genital viral warts were recruited in this open-label clinical study. The patients were treated with oral zinc sulfate (10 mg/kg to a maximum dose of 600 mg/day) for 2 months and followed up with assessments for the resolution of their warts and for any evidence of recurrence after treatment. Among the 31 patients, 18 patients showed low serum zinc levels (58%). Of 26 patients who completed the study (84%), 13 (50%) showed complete resolution of their warts after 2 months of treatment. Complete responders remained free of lesions at 6-month follow-up. No serious side-effects were reported apart from nausea (16%), mild gastric pain (3%) and itching sensation (3%). Oral zinc sulfate was found to be a good option in the treatment of viral warts, as it was safe and effective without important side-effects. © 2010 Japanese Dermatological Association.

  4. EFFICACY AND SAFETY OF SIMVASTATIN IN RHEUMATOID ARTHRITIS: AN OPEN-LABEL, CONTROLLED STUDY

    Directory of Open Access Journals (Sweden)

    I. V. Shirinsky

    2008-01-01

    Full Text Available Abstract. Recently discovered immune–modulating and anti-inflammatory properties of statins have resulted in application of these drugs for treatment of autoimmune disorders. There are few studies investigating therapeutic potential of simvastatin in rheumatoid arthritis (RA. In present study, we investigated efficacy and safety of simvastatin in active RA patients treated with conventional disease-modifying antirheumatic drugs (DMARDs. Thirty-three patients were enrolled into an open-label, controlled study. The patients received treatment with 40 mg of simvastatin daily for 12 weeks. A group of historical controls consisted of nine patients taking placebo combined with disease-modifying therapy. No differences in demographic characteristics and disease activity were observed between the two groups. By the end of therapy (12 weeks, simvastatin-treated patients exhibited a significant reduction in disease activity scores with 28-joint counts (DAS28, and according to physician’s assessment of disease, as compared with control group. The estimate of trea tment effect (DAS28 scores was 0.76 (95% confidence interval 0.01-1.5, thus corresponding to moderate decrease in disease activity. In conclusion, combination therapy with simvastatin and conventional DMARDs results into decreased RA activity. However, additional studies are required in order to specify exact role of simvastatin in RA treatment. (Med. Immunol., vol. 10, N 4-5, pp 477-482.

  5. Outcomes of autologous bone marrow mononuclear cells for cerebral palsy: an open label uncontrolled clinical trial.

    Science.gov (United States)

    Nguyen, Liem Thanh; Nguyen, Anh Tuan; Vu, Chinh Duy; Ngo, Doan V; Bui, Anh V

    2017-04-12

    Stem cell therapy has emerged as a promising method for improving motor function of patients with cerebral palsy. The aim of this study is to assess the safety and effectiveness of autologous bone marrow mononuclear stem cell transplantation in patients with cerebral palsy related to oxygen deprivation. An open label uncontrolled clinical trial was carried out at Vinmec International Hospital. The intervention consisted of two administrations of stem cells, the first at baseline and the second 3 months later. Improvement was monitored at 3 months and 6 months after the first administration of stem cells, using the Gross Motor Function Measure (GMFM) and Modified Ashworth Score which measures muscle tone. No severe complications were recorded during the study. After transplantation, 12 patients encountered fever without infections and 9 patients experienced vomiting which was easily managed with medications. Gross motor function was markedly improved 3 months or 6 months after stem cell transplantation than at baseline. The post-transplantation GMFM-88 total score, each of its domains and the GMFM-66 percentile were all significantly higher (p-value  0.05). Autologous bone marrow mononuclear cell transplantation appears to be a safe and effective therapy for patients with cerebral palsy. ClinicalTrials.gov Identifier: NCT02569775 . Retrospectively registered on October 15, 2015.

  6. Flaxseed supplementation in non-alcoholic fatty liver disease: a pilot randomized, open labeled, controlled study.

    Science.gov (United States)

    Yari, Zahra; Rahimlou, Mehran; Eslamparast, Tannaz; Ebrahimi-Daryani, Naser; Poustchi, Hossein; Hekmatdoost, Azita

    2016-06-01

    A two-arm randomized open labeled controlled clinical trial was conducted on 50 patients with non-alcoholic fatty liver disease (NAFLD). Participants were assigned to take either a lifestyle modification (LM), or LM +30 g/day brown milled flaxseed for 12 weeks. At the end of the study, body weight, liver enzymes, insulin resistance and hepatic fibrosis and steatosis decreased significantly in both groups (p< 0.05); however, this reduction was significantly greater in those who took flaxseed supplementation (p < 0.05). The significant mean differences were reached in hepatic markers between flaxseed and control group, respectively: ALT [-11.12 compared with -3.7 U/L; P< 0.001], AST [-8.29 compared with -4 U/L; p < 0.001], GGT [-15.7 compared with -2.62 U/L; p < 0.001], fibrosis score [-1.26 compared with -0.77 kPa; p = 0.013] and steatosis score [-47 compared with -15.45 dB/m; p = 0.022]. In conclusion, flaxseed supplementation plus lifestyle modification is more effective than lifestyle modification alone for NAFLD management.

  7. A randomised, open-label study of umeclidinium versus glycopyrronium in patients with COPD

    Directory of Open Access Journals (Sweden)

    Tara Rheault

    2016-04-01

    Full Text Available This study compared the efficacy and safety of once-daily umeclidinium 62.5 µg with once-daily glycopyrronium 50 µg in patients with moderate-to-severe chronic obstructive pulmonary disease. This was a 12-week, multicentre, randomised, open-label, parallel-group study (Clinicaltrials.gov: NCT02236611. Patients were randomised 1:1 to umeclidinium 62.5 µg or glycopyrronium 50 µg administered via Ellipta or Breezhaler dry powder inhaler, respectively. The primary endpoint was trough forced expiratory volume in 1 s (FEV1 at day 85 in the per-protocol population. Other endpoints included: weighted mean FEV1 over 0–24 h and patient-reported outcomes (transition dyspnoea index score and St George's Respiratory Questionnaire total score. Adverse events were also assessed. A total of 1037 patients were randomised to treatment. Umeclidinium was non-inferior (margin: −50 mL to glycopyrronium (trough FEV1 at day 85 treatment difference: 24 mL, 95% confidence intervals: −5–54. Improvements in other endpoints were similar between treatments. Adverse event incidences were similar for umeclidinium (37% and glycopyrronium (36%. Once-daily umeclidinium was non-inferior to once-daily glycopyrronium in patients with chronic obstructive pulmonary disease in trough FEV1 at day 85. Patient-reported outcomes and safety profiles were similar for both treatments.

  8. A randomised, open-label study of umeclidinium versus glycopyrronium in patients with COPD.

    Science.gov (United States)

    Rheault, Tara; Khindri, Sanjeev; Vahdati-Bolouri, Mitra; Church, Alison; Fahy, William A

    2016-04-01

    This study compared the efficacy and safety of once-daily umeclidinium 62.5 µg with once-daily glycopyrronium 50 µg in patients with moderate-to-severe chronic obstructive pulmonary disease. This was a 12-week, multicentre, randomised, open-label, parallel-group study (Clinicaltrials.gov: NCT02236611). Patients were randomised 1:1 to umeclidinium 62.5 µg or glycopyrronium 50 µg administered via Ellipta or Breezhaler dry powder inhaler, respectively. The primary endpoint was trough forced expiratory volume in 1 s (FEV1) at day 85 in the per-protocol population. Other endpoints included: weighted mean FEV1 over 0-24 h and patient-reported outcomes (transition dyspnoea index score and St George's Respiratory Questionnaire total score). Adverse events were also assessed. A total of 1037 patients were randomised to treatment. Umeclidinium was non-inferior (margin: -50 mL) to glycopyrronium (trough FEV1 at day 85 treatment difference: 24 mL, 95% confidence intervals: -5-54). Improvements in other endpoints were similar between treatments. Adverse event incidences were similar for umeclidinium (37%) and glycopyrronium (36%). Once-daily umeclidinium was non-inferior to once-daily glycopyrronium in patients with chronic obstructive pulmonary disease in trough FEV1 at day 85. Patient-reported outcomes and safety profiles were similar for both treatments.

  9. An Open-Label Trial of Memantine for Cognitive Impairment in Patients with Posttraumatic Stress Disorder

    Science.gov (United States)

    Ramaswamy, Sriram; Madabushi, Jayakrishna; Hunziker, John; Bhatia, Subhash C.; Petty, Frederick

    2015-01-01

    Background. Studies using standard neuropsychological instruments have demonstrated memory deficits in patients with PTSD. We evaluated the efficacy and safety of the N-methyl-D-aspartate antagonist memantine in veterans with PTSD and cognitive impairment. Methods. Twenty-six veterans with PTSD and cognitive impairment received 16 weeks of memantine in an open-label fashion. Cognition was assessed using the Spatial Span, Logical Memory I, and Letter-Number Sequencing subtests of the Wechsler Memory Scale III and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). RBANS measures attention, language, visuospatial skills, and immediate and delayed memories. The Clinician Administered PTSD Scale (CAPS), Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale (HAM-A), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), and Sheehan Disability Scale (SDS) were secondary outcome measures. Results. There was a significant improvement in RBANS, both total and subscale scores (P < 0.05), over time. There was a reduction in total CAPS scores, avoidance/numbing symptoms (CAPS-C) and hyperarousal symptoms (CAPS-D), HAM-D, Q-LES-Q, and SDS scores. However, there was no reduction in reexperiencing (CAPS-B) and HAM-A scores. Memantine was well tolerated. Conclusions. Memantine improved cognitive symptoms, PTSD symptoms, and mood in veterans with PTSD. Randomized double-blind studies are needed to validate these preliminary observations. PMID:26064685

  10. Homoeopathic management of Schizophrenia: A prospective, non-comparative, open-label observational study

    Directory of Open Access Journals (Sweden)

    Praveen Oberai

    2016-01-01

    Full Text Available Objectives: To evaluate the usefulness of homoeopathic intervention in Schizophrenia, in untreated cases and antipsychotic treatment resistant cases, to verify indications of medicines, and to assess relapse, if any. Materials and Methods: A prospective, non-comparative, open-label observational study was carried out from October 2005-September 2010 by CCRH at Central Research Institute (H, Kottayam, Kerala, India. Patients between 20 and 60 years of age, presenting with symptoms of Schizophrenia were screened for inclusion and exclusion criteria. The patients who were on antipsychotic drugs were allowed to continue the same along with homoeopathic medicine, the dose of antipsychotics was monitored by the Psychiatrist. The symptoms of each patient were repertorized, and medicine was initially prescribed in 30C potency after consulting Materia Medica. Patients were followed up for 12 months. Outcome of treatment was assessed with Brief Psychiatric Rating Scales (BPRS. Analysis was done using Statistical Package for the Social Sciences  SPSS Version 20.0. Results: Out of 188 enrolled patients, 17 cases did not complete the baseline information. Total 171 patients were analysed as per modified Intention to Treat Principle. Significant difference (P = 0.0001, P < 0.05 in the mean scores of BPRS, using paired t test was observed at end of the study. Sulphur, Lycopodium, Natrum muriaticum, Pulsatilla and Phosphorus were found to be the most useful medicines in treating schizophrenic patients. Conclusion: The study reflects the positive role of homoeopathic medicines in the management of patients suffering from schizophrenia as measured by BPRS.

  11. An open-label conversion study of pramipexole to ropinirole prolonged release in Parkinson's disease.

    Science.gov (United States)

    Lyons, Kelly E; Pahwa, Rajesh

    2009-10-30

    Ropinirole prolonged release (PR) is a once daily oral dopamine agonist approved for the treatment of Parkinson's disease (PD). The goal of this 4 week, open-label study was to determine the most effective conversion ratio with the fewest adverse effects (AEs) when switching from pramipexole to ropinirole PR. Sixty patients with PD taking pramipexole were converted overnight to ropinirole PR at ratios of 1:3, 1:4, or 1:5 such that 20 consecutive subjects were enrolled in each group. Ropinirole PR dose adjustments were allowed to maintain efficacy or to reduce AEs. An overnight switch from pramipexole to ropinirole PR was found to be well tolerated and AEs were typical for a dopamine agonist. The most common AEs were worsening of PD symptoms, dizziness, somnolence, and nausea, the majority of which resolved after dose adjustments. Thirteen subjects discontinued ropinirole PR before 4 weeks. These subjects were taking a significantly greater dose of pramipexole, the majority greater than 4 mg/day, and tended to have longer disease durations. A conversion ratio of 1 mg of pramipexole to 4 mg of ropinirole PR resulted in the fewest discontinuations of ropinirole PR, the fewest dose adjustments and the largest percentage of subjects that preferred ropinirole PR.

  12. Autologous Bone Marrow Mononuclear Cell Therapy for Autism: An Open Label Proof of Concept Study

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    Alok Sharma

    2013-01-01

    Full Text Available Cellular therapy is an emerging therapeutic modality with a great potential for the treatment of autism. Recent findings show that the major underlying pathogenetic mechanisms of autism are hypoperfusion and immune alterations in the brain. So conceptually, cellular therapy which facilitates counteractive processes of improving perfusion by angiogenesis and balancing inflammation by immune regulation would exhibit beneficial clinical effects in patients with autism. This is an open label proof of concept study of autologous bone marrow mononuclear cells (BMMNCs intrathecal transplantation in 32 patients with autism followed by multidisciplinary therapies. All patients were followed up for 26 months (mean 12.7. Outcome measures used were ISAA, CGI, and FIM/Wee-FIM scales. Positron Emission Tomography-Computed Tomography (PET-CT scan recorded objective changes. Out of 32 patients, a total of 29 (91% patients improved on total ISAA scores and 20 patients (62% showed decreased severity on CGI-I. The difference between pre- and postscores was statistically significant (P<0.001 on Wilcoxon matched-pairs signed rank test. On CGI-II 96% of patients showed global improvement. The efficacy was measured on CGI-III efficacy index. Few adverse events including seizures in three patients were controlled with medications. The encouraging results of this leading clinical study provide future directions for application of cellular therapy in autism.

  13. Open-label pilot study of memantine in the treatment of compulsive buying.

    Science.gov (United States)

    Grant, Jon E; Odlaug, Brian L; Mooney, Marc; O'Brien, Robert; Kim, Suck Won

    2012-05-01

    Although compulsive buying (CB) is relatively common, pharmacotherapy research for CB is limited. Memantine, an N-methyl-D-aspartate receptor antagonist, appears to reduce glutamate excitability and improve impulsive behaviors, suggesting it may help individuals with CB. Nine patients (8 females) with CB were enrolled in a 10-week open-label treatment study of memantine (dose ranging from 10 to 30 mg/d). Participants were enrolled from December 2008 until May 2010. The primary outcome measure was change from baseline to study endpoint on the Yale-Brown Obsessive Compulsive Scale-Shopping Version (Y-BOCS-SV). Of the 9 participants, 8 (88.9%) completed the 10-week study. Y-BOCS-SV scores decreased from a mean of 22.0 ± 1.3 at baseline to 11.0 ± 5.3 at endpoint (P buying and improvements on cognitive tasks of impulsivity. In addition, the medication was well-tolerated. These findings suggest that pharmacologic manipulation of the glutamate system may target the impulsive behavior underlying CB. Placebo-controlled, double-blind studies are warranted in order to confirm these preliminary findings in a controlled design.

  14. Neural correlates of change in major depressive disorder anhedonia following open-label ketamine.

    Science.gov (United States)

    Lally, Níall; Nugent, Allison C; Luckenbaugh, David A; Niciu, Mark J; Roiser, Jonathan P; Zarate, Carlos A

    2015-05-01

    Anhedonia is a cardinal symptom of major depression and is often refractory to standard treatment, yet no approved medication for this specific symptom exists. In this exploratory re-analysis, we assessed whether administration of rapid-acting antidepressant ketamine was associated specifically with reduced anhedonia in medication-free treatment-refractory patients with major depressive disorder in an open-label investigation. Additionally, participants received either oral riluzole or placebo daily beginning 4 hours post-infusion. A subgroup of patients underwent fluorodeoxyglucose positron emission tomography scans at baseline (1-3 days pre-infusion) and 2 hours post-ketamine infusion. Anhedonia rapidly decreased following a single ketamine infusion; this was sustained for up to three days, but was not altered by riluzole. Reduced anhedonia correlated with increased glucose metabolism in the hippocampus and dorsal anterior cingulate cortex (dACC) and decreased metabolism in the inferior frontal gyrus and orbitofrontal cortex (OFC). The tentative relationship between change in anhedonia and glucose metabolism remained significant in dACC and OFC, and at trend level in the hippocampus, a result not anticipated, when controlling for change in total depression score. Results, however, remain tenuous due to the lack of a placebo control for ketamine. In addition to alleviating overall depressive symptoms, ketamine could possess anti-anhedonic potential in major depressive disorder, which speculatively, may be mediated by alterations in metabolic activity in the hippocampus, dACC and OFC. © The Author(s) 2015.

  15. Open-label study of duloxetine for the treatment of obsessive-compulsive disorder.

    Science.gov (United States)

    Dougherty, Darin D; Corse, Andrew K; Chou, Tina; Duffy, Amanda; Arulpragasam, Amanda R; Deckersbach, Thilo; Jenike, Michael A; Keuthen, Nancy J

    2015-01-01

    This study sought to investigate the efficacy of duloxetine for the treatment of obsessive-compulsive disorder (DSM-IV). Twenty individuals were enrolled in a 17-week, open-label trial of duloxetine at Massachusetts General Hospital. Data were collected between March 2007 and September 2012. Study measures assessing obsessive-compulsive disorder symptoms, quality of life, depression, and anxiety were administered at baseline and weeks 1, 5, 9, 13, and 17. The primary outcome measures were the Yale-Brown Obsessive Compulsive Scale and Clinical Global Improvement scale. For the 12 study completers, pre- and posttreatment analyses revealed significant improvements (Pobsessive-compulsive disorder symptoms and quality of life. Among the 12 completers, more than one-half (n=7) satisfied full medication response criteria. Intention-to-treat analyses (n=20) showed similar improvements (Pobsessive-compulsive disorder. ClinicalTrials.gov NCT00464698; http://clinicaltrials.gov/ct2/show/NCT00464698?term=NCT00464698&rank=1. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  16. A multicenter,phase III trial of hemocoagulase Agkistrodon:hemostasis,coagulation,and safety in patients undergoing abdominal surgery

    Institute of Scientific and Technical Information of China (English)

    WEI Jun-min; LI Jie; XU Jing-yong; ZHENG Qing-shan; ZHU Ming-wei; ZHANG Zhong-tao; JIA Zhen-geng; HE Xiao-dong; WAN Yuan-lian; WANG Shan; XIU Dian-rong; TANG Yun

    2010-01-01

    Background Hemocoagulase Agkistrodon for injection is a single component thrombin which has passed phases I and II clinical trials. The purpose of this phase III clinical trial was to evaluate the effect of Hemocoagulase Agkistrodon on hemostasis and coagulation in abdominal skin and subcutaneous incisions and to assess the safety of this agent in surgical patients. Methods This is a phase III, prospective, randomized, double-blind, and controlled multicenter clinical trial including 432 consecutive patients randomized into either a study group (injected with hemocoagulase Agkistrodon at 2 U, n=324) or a control group (injected with hemocoagulase Atrox, n=108). The hemostatic time, hemorrhagic volume, hemorrhagic volume per unit area, blood coagulation, and adverse events were measured and compared between the two groups. Results The mean hemostatic time in the study group was (36.8±18.7) seconds; the hemorrhagic volume was (3.77±3.93) g; and the hemorrhagic volume per unit area was (0.091±0.125) g/cm~2. In the control group, the corresponding values were (38.1±19.7) seconds, (4.00±4.75) g, and (0.095±0.101) g/cm~2, respectively. No significant difference in values existed between the two groups (P >0.05). Blood coagulation results and hepatic and renal function were also similar between the two groups. Adverse events were reported in two cases, but were deemed non-drug-related. Conclusions Hemocoagulase Agkistrodon has good hemostatic and coagulative function and is safe for the use of arresting capillary hemorrhage that occurs while incising the abdomen during surgery.

  17. Multicenter phase II study of matured dendritic cells pulsed with melanoma cell line lysates in patients with advanced melanoma

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    Hernandez Jackie

    2010-09-01

    Full Text Available Abstract Background Several single center studies have provided evidence of immune activation and antitumor activity of therapeutic vaccination with dendritic cells (DC in patients with metastatic melanoma. The efficacy of this approach in patients with favorable prognosis metastatic melanoma limited to the skin, subcutaneous tissues and lung (stages IIIc, M1a, M1b was tested in a multicenter two stage phase 2 study with centralized DC manufacturing. Methods The vaccine (IDD-3 consisted 8 doses of autologous monocyte-derived matured DC generated in serum-free medium with granulocyte macrophage colony stimulating factor (GM-CSF and interleukin-13 (IL-13, pulsed with lysates of three allogeneic melanoma cell lines, and matured with interferon gamma. The primary endpoint was antitumor activity. Results Among 33 patients who received IDD-3 there was one complete response (CR, two partial responses (PR, and six patients had stable disease (SD lasting more than eight weeks. The overall prospectively defined tumor growth control rate was 27% (90% confidence interval of 13-46%. IDD-3 administration had minimal toxicity and it resulted in a high frequency of immune activation to immunizing melanoma antigens as assessed by in vitro immune monitoring assays. Conclusions The administration of matured DC loaded with tumor lysates has significant immunogenicity and antitumor activity in patients with limited metastatic melanoma. Clinical trial registration NCT00107159.

  18. Amantadine augmentation therapy for obsessive compulsive patients resistant to SSRIs-an open-label study.

    Science.gov (United States)

    Stryjer, Rafael; Budnik, Dana; Ebert, Tania; Green, Tamar; Polak, Lea; Weizman, Shira; Spivak, Baruch

    2014-01-01

    It has been hypothesized that glutamatergic dysfunction may play a role in the development of obsessive compulsive disorder (OCD) and that glutamatergic modulation may ameliorate some of the OC symptoms. We evaluated the effectiveness of amantadine (AMN)- a weak, noncompetitive, antagonist of the N-methyl-D-aspartic acid (NMDA) receptor-as an adjunctive therapy to selective serotonin reuptake inhibitors (SSRIs), and its role in improving OC symptoms in cases refractory to SSRI pharmacotherapy alone. Eight patients (5 males and 3 females, aged 42.6 ± 13.1 years) that met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for OCD, scored above 20 points on Yale Brown Obsessive Compulsive Scale (Y-BOCS) and were unresponsive to at least one SSRI, completed an open label study of 6 weeks duration. AMN was added to the current stable SSRI regimen and baseline and endpoint changes in Y-BOCS, depression and anxiety levels were analyzed. Significant reductions in total Y-BOCS (28 ± 4.5 vs. 18.8 ± 8.8; P < 0.01; df = 7; t = 2.36), Y-BOCS compulsion sub-scale (15.3 ± 3.2 vs. 10.6 ± 4.7; P < 0.02; df = 7; t = 2.36), and Y-BOCS obsession sub-scale (12.7 ± 3.3 vs. 8.1 ± 5; P < 0.05; df = 7; t = 2.36) scores were obtained at endpoint. The anxiety and depression levels remained unaltered. AMN adjunction to SSRI treatment may lead to a significant reduction in OC symptoms, supporting the hypothesis that transduction of the glutamate signal via NMDA receptor may play a role in OCD. A large scale, double-blind, placebo-controlled study is warranted to confirm our results.

  19. Dexmedetomidine versus propofol in dilatation and curettage: An open-label pilot randomized controlled trial

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    Priyanka Sethi

    2015-01-01

    Full Text Available Background: Traditionally propofol has been used for providing sedation in dilatation and curettage (D and C. Recently, dexmedetomidine has been tried, but very little evidence exists to support its use. Aims: The aim was to compare hemodynamic and recovery profile of both the drugs along with a degree of comfort experienced by patients and the usefulness of the drug to surgeons. Settings and Design: Tertiary care center and open-label randomized controlled trial. Materials and Methods: Patients posted for D and C were enrolled in two groups (25 each. Both groups received fentanyl 1 μg/kg intravenous (IV at the beginning of the procedure. Group P received IV propofol in dose of 1.5 mg/kg over 10-15 min and Group D received dexmedetomidine at a loading dose of 1 μg/kg over 10 min, followed by 0.5 μg/kg/h infusion until Ramsay sedation score reached 3-4. Hemodynamic vitals were compared during and after the procedure. In the recovery room time to reach modified Aldrete score (MAS of 9-10 and patient′s and surgeon′s satisfaction scores were also recorded and compared. Results: In Group D, patients had statistically significant lower heart rate at 2, 5, 10 and 15 min as compared to Group P. Hypotension was present in 52% in Group P and 4% in Group D (P < 0.05. MAS of 9-10 was achieved in 4.4 min in subjects in Group D in contrast to 16.2 min in Group P (P < 0.05. Group D showed higher patient and surgeon satisfaction scores (P < 0.05. Conclusion: Dexmedetomidine provide better hemodynamic and recovery profile than propofol. It can be a superior alternative for short surgical day care procedures.

  20. An open-label pilot trial of minocycline in children as a treatment for Angelman syndrome.

    Science.gov (United States)

    Grieco, Joseph C; Ciarlone, Stephanie L; Gieron-Korthals, Maria; Schoenberg, Mike R; Smith, Amanda G; Philpot, Rex M; Heussler, Helen S; Banko, Jessica L; Weeber, Edwin J

    2014-12-10

    Minocycline, a member of the tetracycline family, has a low risk of adverse effects and an ability to improve behavioral performance in humans with cognitive disruption. We performed a single-arm open-label trial in which 25 children diagnosed with Angelman syndrome (AS) were administered minocycline to assess the safety and tolerability of minocycline in this patient population and determine the drug's effect on the cognitive and behavioral manifestations of the disorder. Participants, age 4-12 years old, were randomly selected from a pool of previously screened children for participation in this study. Each child received 3 milligrams of minocycline per kilogram of body weight per day for 8 weeks. Participants were assessed during 3 study visits: baseline, after 8-weeks of minocycline treatment and after an 8-week wash out period. The primary outcome measure was the Bayley Scales of Infant and Toddler Development 3rd Edition (BSID-III). Secondary outcome measures included the Clinical Global Impressions Scale (CGI), Vineland Adaptive Behavior Scales 2nd Edition (VABS-II), Preschool Language Scale 4th Edition (PLS-IV) and EEG scores. Observations were considered statistically significant if p VABS-II after treatment with minocycline. Finally, mean scores of the BSID-III self-direction subdomain and CGI scale score were significantly improved both after minocycline treatment and after the wash out period. The clinical and neuropsychological measures suggest minocycline was well tolerated and causes improvements in the adaptive behaviors of this sample of children with Angelman syndrome. While the optimal dosage and the effects of long-term use still need to be determined, these findings suggest further investigation into the effect minocycline has on patients with Angelman syndrome is warranted. NCT01531582 - clinicaltrials.gov.

  1. Nerve Growth Factor for the Treatment of Spinocerebellar Ataxia Type 3: An Open-label Study

    Institute of Scientific and Technical Information of China (English)

    Song Tan; Rui-Hao Wang; Hui-Xia Niu; Chang-He Shi; Cheng-Yuan Mao; Rui Zhang; Bo Song

    2015-01-01

    Background:Spinocerebellar ataxia type 3 (SCA3) is the most common subtype of SCA worldwide,and runs a slowly progressive and unremitting disease course.There is currently no curable treatment available.Growing evidence has suggested that nerve growth factor (NGF) may have therapeutic effects in neurodegenerative diseases,and possibly also in SCA3.The objective of this study was to test the efficacy of NGF in SCA3 patients.Methods:We performed an open-label prospective study in genetically confirmed adult (>18 years old) SCA3 patients.NGF was administered by intramuscular injection (18 μg once daily) for 28 days consecutively.All the patients were evaluated at baseline and 2 and 4 weeks after treatment using the Chinese version of the scale for assessment and rating of ataxia (SARA).Results:Twenty-one SCA3 patients (10 men and 11 women,mean age 39.14 ± 7.81 years,mean disease duration 4.14 ± 1.90 years,mean CAG repeats number 77.57 ± 2.27) were enrolled.After 28 days of NGF treatment,the mean total SARA score decreased significantly from a baseline of 8.48 ± 2.40 to 6.30 ± 1.87 (P < 0.001).Subsections SARA scores also showed significant improvements in stance (P =0.003),speech (P =0.023),finger chase (P =0.015),fast alternating hand movements (P =0.009),and heel-shin slide (P =0.001).Conclusions:Our preliminary data suggest that NGF may be effective in treating patients with SCA3.

  2. An open-label study of quetiapine in the treatment of fibromyalgia.

    Science.gov (United States)

    Hidalgo, Javier; Rico-Villademoros, Fernando; Calandre, Elena Pita

    2007-01-30

    The aim of this exploratory study was to systematically assess the potential effectiveness and tolerability of quetiapine, an atypical antipsychotic, for the treatment of patients with fibromyalgia. This was a unicentre, open-label study conducted in thirty-five outpatients, 18 years or older, who met the ACR criteria for fibromyalgia and who had not satisfactorily responded to their previous fibromyalgia treatment. Quetiapine, flexibly dosed (25-100 mg/day), was added to their original treatment regimen for 12 weeks. The primary outcome measure was the mean change from baseline to endpoint in the Fibromyalgia Impact Questionnaire (FIQ) total score. Secondary efficacy measures included mean changes from baseline to endpoint in the scores of the Clinical Global Impression (CGI) of Severity scale, Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), 12-Item Short Form Health Survey (SF-12), and individual items of the FIQ. Thirty (85.7%) patients (mean age 47+/-7.9, 93.3% females) had a postbaseline evaluation and constituted the intent-to-treat efficacy sample. Mean FIQ total score decreased significantly by 10.2 points from a baseline of 63.2 to 53.0 at study endpoint (pfatigue subscores but not in FIQ pain subscore. Large effect sizes were observed for the FIQ total (1.04), CGI-severity (1.00) and PSQI (1.07), while moderate effect sizes (i.e.> or =0.50) were encountered in the FIQ fatigue, FIQ stiffness and SF-12 mental component summary. Quetiapine was safely administered and well tolerated. Despite the lack of effect on pain, the significant and relevant improvement in overall efficacy measures and quality of life suggests that quetiapine may be a valuable drug for treatment of patients with fibromyalgia that should be further tested in double-blind, placebo-controlled trials.

  3. Open-Label Treatment of Moderate or Marked Melasma with a 4% Hydroquinone Skin Care System Plus 0.05% Tretinoin Cream

    Science.gov (United States)

    Rendon, Marta; Dibernardo, Barry; Bruce, Suzanne; Lucas-Anthony, Chere; Watson, Joanne

    2013-01-01

    Objective: To evaluate treating epidermal melasma using a 4% hydroquinone skin care system plus tretinoin 0.05% cream. Design: Multicenter open-label study with all patients receiving above-mentioned treatment for up to 24 weeks. Setting: Private dermatology and plastic surgery clinics and clinical research facilities. Participants: Thirty-seven adult females with moderate or marked epidermal melasma, melasma pigmentation of mild-to-marked intensity and Fitzpatrick skin type III to VI. Measurements: Melasma severity melasma pigmentation intensity melasma improvement, patient satisfaction, quality-of-life measures, erythema, dryness, peeling, burning/stinging. Results: No patient discontinued due to lack of efficacy or treatment-related adverse events. Treatment was associated with a significant reduction from baseline in melasma severity and melasma pigmentation intensity from Week 4 onward (P≤0.001), and 100 percent of patients showed improvement from Week 8 onward. At Week 24, 100 percent of patients were “satisfied” or “very satisfied” with the overall effectiveness of their treatment. Patients’ quality of life also improved (e.g., the proportion of patients feeling embarrassed or self-conscious about their skin “a lot” or “very much” declined from 78 percent at baseline to four percent at Week 24). Mean and median scores for erythema, dryness, peeling, and burning/stinging did not exceed trace levels. Conclusion: Treating moderate-to-severe melasma using the 4% hydroquinone skin care system plus 0.05% tretinoin can significantly reduce the severity of melasma and the intensity of melasma pigmentation within four weeks. Treatment was generally well tolerated and associated with an improved quality of life and high levels of patient satisfaction. PMID:24307923

  4. A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients.

    Science.gov (United States)

    Davis, Gary L; Nelson, David R; Terrault, Norah; Pruett, Timothy L; Schiano, Thomas D; Fletcher, Courtney V; Sapan, Christine V; Riser, Laura N; Li, Yufeng; Whitley, Richard J; Gnann, John W

    2005-08-01

    Chronic hepatitis C is the most common indication for liver transplantation, but viral recurrence is universal and progressive graft injury occurs in most recipients. Our aim was to assess the safety, pharmacokinetics (PK), and antiviral effects of high doses of a human hepatitis C antibody enriched immune globulin product (HCIG) in patients undergoing liver transplantation for chronic hepatitis C. This was a multicenter, randomized, open-label, controlled trial conducted at 4 transplant centers in the United States. A total of 18 patients with chronic hepatitis C, who underwent liver transplantation, were randomized to receive low-dose HCIG (75 mg/kg) or high-dose HCIG (200 mg/kg), or no treatment. A total of 17 infusions of HCIG were administered in each treated patient over 14 weeks using a time-dependent dosing strategy based on the PK of anti-hepatitis B immune globulin in liver transplant recipients. Hepatitis C virus levels, liver enzymes, and liver biopsies were obtained serially throughout the study period. PK profiles of HCV antibodies were determined on days 4, 10, and 98. HCIG infusions were safe and tolerated. The infusion rate could not be maximized because of symptoms for 18% to 30% of the doses. The half-life of HCIG was extremely short immediately after transplantation but was gradually prolonged. In the high-dose group, serum alanine aminotransferase (ALT) levels normalized in most subjects and no patient developed hepatic fibrosis. However, serum HCV RNA levels were not suppressed at either dose. In conclusion, HCIG, an anti-HCV enriched immune globulin product, appears to be safe in patients with chronic hepatitis C undergoing liver transplantation. Further studies are required to determine whether the drug has beneficial effects in this group of patients.

  5. Single-arm open-label study of Durolane (NASHA nonanimal hyaluronic acid) for the treatment of osteoarthritis of the thumb

    Science.gov (United States)

    Velasco, Eloisa; Ribera, Mª Victoria; Pi, Joan

    2017-01-01

    Introduction Osteoarthritis of the trapeziometacarpal (TMC) joint of the thumb – also known as rhizarthrosis – is painful and has a significant impact on quality of life. Intra-articular injection of hyaluronic acid may potentially meet the need for effective, minimally invasive intervention in patients not responding adequately to initial treatment. We aimed to confirm the safety and effectiveness of viscosupplementation with Durolane (NASHA nonanimal hyaluronic acid) in rhizarthrosis. Patients and methods This was a prospective, single-arm, multicenter, open-label study with a 6-month follow-up period. Eligible patients had Eaton–Littler grade II–III rhizarthrosis in one TMC joint with pain and visual analog scale (VAS) pain score ≥4 (scale: 0–10). A single injection of NASHA was administered to the affected TMC joint. The primary effectiveness variable was change from baseline in VAS pain score. Results Thirty-five patients (mean age 60.8 years; 85.7% female) received NASHA and completed the study. The least-squares mean change from baseline in VAS pain score over 6 months was −2.00, a reduction of 27.8% (pKapandji thumb opposition test, radial abduction, metacarpophalangeal (MCP) joint flexion, and pinch (clamp) strength. Most of these measurements showed statistically significant improvements from baseline over 6 months. Five adverse events (injection site reactions) were reported in four patients (11.4%), and there were no serious or allergic reactions. Conclusion This study suggests that viscosupplementation using NASHA is effective and well tolerated in treating the symptoms of rhizarthrosis. PMID:28392718

  6. Polyacrylamide hydrogel injection in the management of human immunodeficiency virus-related facial lipoatrophy: results of the LIPOPHILL open-label study.

    Science.gov (United States)

    Mole, Bernard; Gillaizeau, Florence; Carbonnel, Elisabeth; Pierre, Isabelle; Brazille, Patricia; Grataloup, Christine; Mercier, Sylvie; Duracinsky, Martin; Weiss, Laurence; Piketty, Christophe

    2012-03-01

    Combination antiretroviral therapy (cART) can cause potentially stigmatizing facial lipoatrophy. Encouraging preliminary results have been reported with 2.5% polyacrylamide hydrogel for facial reconstruction. The aim of this multicenter, open-label noncomparative pilot study was to evaluate the efficacy and safety of intradermal facial injections of polyacrylamide hydrogel in HIV-infected patients with severe facial lipoatrophy. The patients received between two and six injections every 4 weeks, according to the aesthetic results. Clinical efficacy was evaluated by means of facial ultrasonography and photography at baseline and months 6, 12, and 24. Adverse events, patient satisfaction, and quality of life were also assessed. One hundred and eleven patients were enrolled and received at least one injection. Mean cheek skin thickness was 9.7 mm [95% CI: 9.1 to 10.2] at baseline. It rose by an average of 4.4 mm [95% CI: 3.9 to 4.9; p<0.001] at month 12 and a further 0.87 mm [95% CI: 0.52 to 1.23; p<0.001] at month 24. The Overall Treatment Satisfaction scale showed an improvement in more than 88% of patients at all visits, based on the appreciations of the patients, their close relatives and physicians, and on independent assessment of facial photographs. Quality of life improved significantly over time, as shown by the lipodystrophy-specific ABCD scale. No severe adverse effects related to the polyacrylamide hydrogel were noted. Polyacrylamide hydrogel injections were well tolerated and significantly improved the aesthetic aspect and quality of life of HIV-infected patients with facial lipoatrophy.

  7. Long-term tolerability of tolterodine extended release in children 5-11 years of age: results from a 12-month, open-label study.

    Science.gov (United States)

    Nijman, Rien J M; Borgstein, Niels G; Ellsworth, Pamela; Siggaard, Charlotte

    2007-11-01

    To evaluate the long-term tolerability of tolterodine extended release (ER) in children (aged 5-11 yr) with urgency urinary incontinence (UUI). This was a multicenter, open-label extension of a 12-wk, double-blind, placebo-controlled study of tolterodine ER. Patients had UUI suggestive of detrusor overactivity (>/=1 diurnal incontinence episode per 24h for >/=5 of 7 d) and >/=6 voids per 24h at baseline and had completed the 12-wk double-blind study. Patients received tolterodine ER (2mg once daily) for 12 mo. The primary end points were the incidence and severity of adverse events (AEs) and the incidence and reasons for withdrawals. Visits were scheduled at 3, 6, 9, and 12 mo, and investigators were instructed to report all AEs. At 6 and 12 mo, vital signs were recorded and a physical examination was performed. A total of 318 patients were enrolled (double-blind tolterodine ER, n=221; placebo, n=97). The majority of patients were white (90%), mean+/-SD age was 7.6+/-1.5 yr, and 54% were boys. Forty-nine percent of patients reported >/=1 AE during the study, similar to that observed in the preceding 12-wk study (42%). The most frequent AEs were urinary tract infection (7%), nasopharyngitis (5%), headache (5%), and abdominal pain (4%); 111 (35%) patients withdrew. The most common reasons for withdrawal were lack of efficacy (12%), symptom improvement (8%), and withdrawn consent (6%). Ten patients (3%) withdrew because of AEs. Long-term treatment with tolterodine ER was well tolerated in children with UUI.

  8. Efficacy and safety of tolterodine in subjects with symptoms of overactive bladder: An open label, noncomparative, prospective, multicentric study

    OpenAIRE

    Anant Kumar

    2002-01-01

    Objective: To evaluate the clinical efficacy and safety of Tolterodine 2 mg twice daily in Indian subjects with symptoms of overactive bladder including frequency, ur-gency with or without urge incontinence. Methods: This multicentric open-label, noncompara-tive, prospective study was conducted at 7 centers across India. Eligible patients were assigned to treatment with Tab. Tolterodine 2 mg twice daily for 8 weeks. Subjects were seen at visit ](day 3 to 10), visit 2 (day 1) and after 8...

  9. AN OPEN-LABEL EXTENSION STUDY OF PARATHYROID HORMONE RHPTH(1-84) IN ADULTS WITH HYPOPARATHYROIDISM.

    Science.gov (United States)

    Lakatos, Peter; Bajnok, Laszlo; Lagast, Hjalmar; Valkusz, Zsuzsanna

    2016-05-01

    Hypoparathyroidism is characterized by inadequate parathyroid hormone (PTH), resulting in hypocalcemia, hyperphosphatemia, and bone abnormalities. Adults with hypoparathyroidism treated with recombinant human PTH, rhPTH(1-84), in the 24-week, phase III REPLACE study maintained serum calcium despite reductions in oral calcium and active vitamin D. This study assessed the long-term efficacy and safety of rhPTH(1-84) for hypoparathyroidism. This was a 24-week, open-label, flexible-dose extension study of REPLACE (REPEAT) conducted in 3 outpatient centers in Hungary. Patients who previously completed or enrolled in REPLACE received 50 μg/day rhPTH(1-84), escalated to 75 and then to 100 μg/day, if needed, to reduce active vitamin D and oral calcium. The primary endpoint was ≥50% reduction in oral calcium (or ≤500 mg/day) and active vitamin D (or calcitriol ≤0.25 μg/day or alfacalcidol ≤0.50 μg/day) with normocalcemia. Twenty-four patients (n = 16 previously treated with rhPTH[1-84]; n = 8 rhPTH[1-84]-naïve) were enrolled and completed the study. At Week 24, 75% of patients (95% confidence interval [CI], 53.3-90.2%) achieved the study endpoint; 58% eliminated oral calcium and active vitamin D. Urinary calcium, serum phosphate, and calcium × phosphate (Ca × P) product decreased by Week 24. Mean serum bone turnover markers increased with rhPTH(1-84). Treatment-emergent adverse events (TEAEs) were reported by 92% of patients. No serious adverse events (AEs) occurred. This study used a simplified treatment algorithm intended to better mimic typical clinical practice and demonstrated the extended efficacy and safety of rhPTH(1-84) in patients with hypoparathyroidism and confirmed the REPLACE findings. Sustained rhPTH(1-84) efficacy up to 48 weeks was observed despite treatment interruption between studies.

  10. Pharmacokinetic interaction between maraviroc and fosamprenavir-ritonavir: an open-label, fixed-sequence study in healthy subjects.

    Science.gov (United States)

    Vourvahis, Manoli; Plotka, Anna; Mendes da Costa, Laure; Fang, Annie; Heera, Jayvant

    2013-12-01

    This open-label, fixed-sequence, phase 1 study evaluated the pharmacokinetic interaction between maraviroc (MVC) and ritonavir-boosted fosamprenavir (FPV/r) in healthy subjects. In period 1, subjects received 300 mg of MVC twice daily (BID; cohort 1) or once daily (QD; cohort 2) for 5 days. In period 2, cohort 1 subjects received 700/100 mg of FPV/r BID alone on days 1 to 10 and then FPV/r at 700/100 mg BID plus MVC at 300 mg BID on days 11 to 20; cohort 2 subjects received FPV/r at 1,400/100 mg QD alone on days 1 to 10 and then FPV/r at 1,400/100 mg QD plus MVC at 300 mg QD on days 11 to 20. Pharmacokinetic parameters, assessed on day 5 of period 1 and on days 10 and 20 of period 2, included the maximum plasma concentration (Cmax), the concentration at end of dosing interval (Cτ), and the area under the curve over dosing interval (AUCτ). Safety and tolerability were also assessed. MVC geometric mean AUCτ, Cmax, and Cτ were increased by 149, 52, and 374%, respectively, after BID dosing with FPV/r, and by 126, 45, and 80%, respectively, after QD dosing. Amprenavir (the active form of the prodrug fosamprenavir) and ritonavir exposures were decreased in the presence of MVC with amprenavir AUCτ, Cmax, and Cτ decreased by 34 to 36% in the presence of FPV/r plus maraviroc BID and by 15 to 30% with FPV/r plus MVC QD both compared to FPV/r alone. The overall all-causality adverse-event (AE) incidence rate was 96.4%; all AEs were of mild or moderate severity. Commonly reported treatment-related AEs (>20% of patients overall) included diarrhea, fatigue, abdominal discomfort, headache, and nausea. No serious AEs or deaths occurred. In summary, maraviroc exposure increased in the presence of FPV/r, whereas MVC coadministration decreased amprenavir and ritonavir exposures. MVC dosed at 300 mg BID with FPV/r is not recommended due to concerns of lower amprenavir exposures; however, no dose adjustment is warranted with MVC at 150 mg BID in combination with FPV/r based on

  11. Comparison of Iohexol-380 and Iohexol-350 for coronary CT angiography: A multicenter, randomized, double-blind phase 3 trial

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eun Ah; Lee, Whal [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of); Kang, Doo Kyoung [Dept. of Radiology, Ajou University School of Medicine, Suwon (Korea, Republic of); and others

    2016-06-15

    This multi-center, randomized, double-blind, phase 3 trial was conducted to compare the safety and efficacy of contrast agents iohexol-380 and iohexol-350 for coronary CT angiography in healthy subjects. Volunteers were randomized to receive 420 mgI/kg of either iohexol-350 or iohexol-380 using a flow rate of 4 mL/sec. All adverse events were recorded. Two blinded readers independently reviewed the CT images and conflicting results were resolved by a third reader. Luminal attenuations (ascending aorta, left main coronary artery, and left ventricle) in Hounsfield units (HUs) and image quality on a 4-point scale were calculated. A total of 225 subjects were given contrast media (115 with iohexol-380 and 110 with iohexol-350). There was no difference in number of adverse drug reactions between groups: 75 events in 56 (48.7%) of 115 subjects in the iohexol-380 group vs. 74 events in 51 (46.4%) of 110 subjects in the iohexol-350 group (p = 0.690). No severe adverse drug reactions were recorded. Neither group showed an increase in serum creatinine. Significant differences in mean density between the groups was found in the ascending aorta: 375.8 ± 71.4 HU with iohexol-380 vs. 356.3 ± 61.5 HU with iohexol-350 (p = 0.030). No significant differences in image quality scores between both groups were observed for all three anatomic evaluations (all, p > 0.05). Iohexol-380 provides improved enhancement of the ascending aorta and similar attenuation of the coronary arteries without any increase in adverse drug reactions, as compared with iohexol-350 using an identical amount of total iodine.

  12. Closure of mesenteric defects in laparoscopic gastric bypass: a multicentre, randomised, parallel, open-label trial.

    Science.gov (United States)

    Stenberg, Erik; Szabo, Eva; Ågren, Göran; Ottosson, Johan; Marsk, Richard; Lönroth, Hans; Boman, Lars; Magnuson, Anders; Thorell, Anders; Näslund, Ingmar

    2016-04-02

    Small bowel obstruction due to internal hernia is a common and potentially serious complication after laparoscopic gastric bypass surgery. Whether closure of surgically created mesenteric defects might reduce the incidence is unknown, so we did a large randomised trial to investigate. This study was a multicentre, randomised trial with a two-arm, parallel design done at 12 centres for bariatric surgery in Sweden. Patients planned for laparoscopic gastric bypass surgery at any of the participating centres were offered inclusion. During the operation, a concealed envelope was opened and the patient was randomly assigned to either closure of mesenteric defects beneath the jejunojejunostomy and at Petersen's space or non-closure. After surgery, assignment was open label. The main outcomes were reoperation for small bowel obstruction and severe postoperative complications. Outcome data and safety were analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01137201. Between May 1, 2010, and Nov 14, 2011, 2507 patients were recruited to the study and randomly assigned to closure of the mesenteric defects (n=1259) or non-closure (n=1248). 2503 (99·8%) patients had follow-up for severe postoperative complications at day 30 and 2482 (99·0%) patients had follow-up for reoperation due to small bowel obstruction at 25 months. At 3 years after surgery, the cumulative incidence of reoperation because of small bowel obstruction was significantly reduced in the closure group (cumulative probability 0·055 for closure vs 0·102 for non-closure, hazard ratio 0·56, 95% CI 0·41-0·76, p=0·0002). Closure of mesenteric defects increased the risk for severe postoperative complications (54 [4·3%] for closure vs 35 [2·8%] for non-closure, odds ratio 1·55, 95% CI 1·01-2·39, p=0·044), mainly because of kinking of the jejunojejunostomy. The results of our study support the routine closure of the mesenteric defects in laparoscopic

  13. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study.

    Science.gov (United States)

    Carhart-Harris, Robin L; Bolstridge, Mark; Rucker, James; Day, Camilla M J; Erritzoe, David; Kaelen, Mendel; Bloomfield, Michael; Rickard, James A; Forbes, Ben; Feilding, Amanda; Taylor, David; Pilling, Steve; Curran, Valerie H; Nutt, David J

    2016-07-01

    Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression. In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after each session. The primary outcome measure for feasibility was patient-reported intensity of psilocybin's effects. Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up. Depressive symptoms were assessed with standard assessments from 1 week to 3 months after treatment, with the 16-item Quick Inventory of Depressive Symptoms (QIDS) serving as the primary efficacy outcome. This trial is registered with ISRCTN, number ISRCTN14426797. Psilocybin's acute psychedelic effects typically became detectable 30-60 min after dosing, peaked 2-3 h after dosing, and subsided to negligible levels at least 6 h after dosing. Mean self-rated intensity (on a 0-1 scale) was 0·51 (SD 0·36) for the low-dose session and 0·75 (SD 0·27) for the high-dose session. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred. The adverse reactions we noted were transient anxiety during drug onset (all patients), transient confusion or thought disorder (nine patients), mild and transient nausea (four patients), and transient headache (four patients). Relative to baseline, depressive symptoms were markedly reduced 1

  14. An open-label,randomized,cross-over bioequivalence study of lafutidine 10 mg under fasting condition

    Institute of Scientific and Technical Information of China (English)

    Bhupesh; Dewan; Raghuram; Chimata

    2010-01-01

    AIM:To assess the relative bioavailability and pharmacokinetic properties of two formulations(test and reference) of Lafutidine 10 mg.METHODS:The study was performed as an open label,randomized,two-way,two-period,two-treatment,single dose cross-over bioequivalence study,under non-fed condition to compare the pharmacokinetic prof iles of the lafutidine formulation manufactured by Emcure Pharmaceuticals Ltd.,India using an indigenously developed active pharmaceutical ingredient(API) and the commercially available Stogra formulation,of UCB Japan Co.,Ltd.,Japan.The two treatments were separated by a washout period of 5 d.After an overnight fasting period of 10 h,the subjects were administered either the test or the reference medication as per the randomization schedule.Blood samples were collected at intervals up to 24 h,as per the approved protocol.Concentrations of lafutidine in plasma were analyzed by a validated liquid chromatography/tandem mass spectrometry(LC/MS/MS) method,and a non-compartmental model was used for pharmacokinetic analysis.The pharmacokinetic parameters were subjected to a 4-way ANOVA accounting for sequence,subjects,period and treatment.Statistical significance was evaluated at 95% conf idence level(P ≥ 0.05).RESULTS:The mean(±SD) values of the pharmacokinetic parameters(test vs reference) were Cmax(265.15±49.84 ng/mL vs 246.79±29.30 ng/mL,P<0.05),Area under the curve(AUC)(0-t)(1033.13±298.74 ng.h/mL vs 952.93±244.07 ng.h/mL,P < 0.05),AUC(0-∞)(1047.61±301.22 ng.h/mL vs 964.21±246.45 ng.h/mL,P<0.05),and tv2(1.92±0.94 h vs 2.05±1.01 h,P<0.05).The 90% conf idence intervals(CI) for the test/reference ratio of mean Cmax,AUC(0-t),and AUC(0-∞) were within the acceptable range of 80.00 to 125.00.The mean times(± SD) to attain maximal plasma concentration(tmax) of lafutidine were 0.95±0.24 h vs 1.01±0.29 h(P<0.05) for the test and the reference formulations respectively.Both the formulations were well tolerated.

  15. Multicenter, Double-Blind, Randomized, Phase 2 Study Evaluating the Novel Antibiotic Cadazolid in Patients with Clostridium difficile Infection.

    Science.gov (United States)

    Louie, Thomas; Nord, Carl Erik; Talbot, George H; Wilcox, Mark; Gerding, Dale N; Buitrago, Martha; Kracker, Hilke; Charef, Pascal; Cornely, Oliver A

    2015-10-01

    Cadazolid, a novel fluoroquinolone-oxazolidinone antibiotic, exhibits potent in vitro activity against Clostridium difficile, including the epidemic BI/NAP1/027 strain. This multicenter, randomized, double-blind, active reference group, phase 2 study evaluated the efficacy and safety of oral cadazolid in treatment of adult patients with C. difficile infection (CDI). Eligible patients with first occurrence/first recurrence of CDI were randomized 1:1:1:1 to 250, 500, or 1,000 mg cadazolid twice daily (BID) or oral 125 mg vancomycin four times daily (QID) for 10 days. The primary endpoint was clinical cure at test of cure (48 ± 24 h after the end of treatment; modified intent-to-treat population), defined as resolution of diarrhea with no further CDI treatment required. Secondary endpoints included recurrence rate, sustained clinical response (clinical cure without recurrence), and time to diarrhea resolution. Of 84 patients enrolled, 20, 22, 20, and 22 received 250, 500, or 1,000 mg cadazolid BID or 125 mg vancomycin QID, respectively. The primary endpoint was achieved in 76.5% (80% confidence interval [CI], 58.4, 89.3), 80.0% (63.9, 91.0), 68.4% (51.1, 82.5), and 68.2% (52.3, 81.3) of patients, respectively. There was no evidence of a cadazolid dosage-dependent response. Each dosage of cadazolid resulted in a lower recurrence rate than with vancomycin (18.2 to 25.0% versus 50%). Consequently, higher sustained clinical response rates were observed with cadazolid (46.7 to 60.0%) than with vancomycin (33.3%). The times to diarrhea resolution were similar for cadazolid and vancomycin. Cadazolid was well tolerated, with no safety signal observed. The results of this phase 2 study support further clinical development of cadazolid. (This study has been registered in the United States at ClinicalTrials.gov under registration no. NCT01222702 and in Europe with the European Medicines Agency under registration no. EUDRA-CT 2010-020941-29.).

  16. Adjunctive agomelatine therapy in the treatment of acute bipolar II depression: a preliminary open label study

    Directory of Open Access Journals (Sweden)

    Fornaro M

    2013-02-01

    Full Text Available Michele Fornaro,1 Michael J McCarthy,2,3 Domenico De Berardis,4 Concetta De Pasquale,1 Massimo Tabaton,5 Matteo Martino,6 Salvatore Colicchio,7 Carlo Ignazio Cattaneo,8 Emanuela D'Angelo,9 Pantaleo Fornaro61Department of Formative Sciences, University of Catania, Catania, Italy; 2Department of Psychiatry, Veteran's Affairs San Diego Healthcare System, 3University of California San Diego, La Jolla, CA, USA; 4Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, "ASL 4", Teramo, Italy; 5Department of Internal Medicine and Medical Specialties, University of Genova, Genoa, Italy; 6Department of Neurosciences, Section of Psychiatry, University of Genova, Genoa, Italy; 7Unit of Sleep Medicine, Department of Neuroscience, Catholic University, Rome, Italy; 8National Health System, "ASL 13", Novara, Italy; 9National Health System, "ASL 3", Genoa, ItalyPurpose: The circadian rhythm hypothesis of bipolar disorder (BD suggests a role for melatonin in regulating mood, thus extending the interest toward the melatonergic antidepressant agomelatine as well as type I (acute or II cases of bipolar depression.Patients and methods: Twenty-eight depressed BD-II patients received open label agomelatine (25 mg/bedtime for 6 consecutive weeks as an adjunct to treatment with lithium or valproate, followed by an optional treatment extension of 30 weeks. Measures included the Hamilton depression scale, Pittsburgh Sleep Quality Index, the Clinical Global Impression Scale–Bipolar Version, Young Mania Rating Scale, and body mass index.Results: Intent to treat analysis results demonstrated that 18 of the 28 subjects (64% showed medication response after 6 weeks (primary study endpoint, while 24 of the 28 subjects (86% responded by 36 weeks. When examining primary mood stabilizer treatment, 12 of the 17 (70.6% valproate and six of the 11 (54.5% lithium patients responded by the first endpoint. At 36 weeks, 14 valproate treated (82.4% and 10 lithium

  17. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial.

    Science.gov (United States)

    Devinsky, Orrin; Marsh, Eric; Friedman, Daniel; Thiele, Elizabeth; Laux, Linda; Sullivan, Joseph; Miller, Ian; Flamini, Robert; Wilfong, Angus; Filloux, Francis; Wong, Matthew; Tilton, Nicole; Bruno, Patricia; Bluvstein, Judith; Hedlund, Julie; Kamens, Rebecca; Maclean, Jane; Nangia, Srishti; Singhal, Nilika Shah; Wilson, Carey A; Patel, Anup; Cilio, Maria Roberta

    2016-03-01

    Almost a third of patients with epilepsy have a treatment-resistant form, which is associated with severe morbidity and increased mortality. Cannabis-based treatments for epilepsy have generated much interest, but scientific data are scarce. We aimed to establish whether addition of cannabidiol to existing anti-epileptic regimens would be safe, tolerated, and efficacious in children and young adults with treatment-resistant epilepsy. In this open-label trial, patients (aged 1-30 years) with severe, intractable, childhood-onset, treatment-resistant epilepsy, who were receiving stable doses of antiepileptic drugs before study entry, were enrolled in an expanded-access programme at 11 epilepsy centres across the USA. Patients were given oral cannabidiol at 2-5 mg/kg per day, up-titrated until intolerance or to a maximum dose of 25 mg/kg or 50 mg/kg per day (dependent on study site). The primary objective was to establish the safety and tolerability of cannabidiol and the primary efficacy endpoint was median percentage change in the mean monthly frequency of motor seizures at 12 weeks. The efficacy analysis was by modified intention to treat. Comparisons of the percentage change in frequency of motor seizures were done with a Mann-Whitney U test. Between Jan 15, 2014, and Jan 15, 2015, 214 patients were enrolled; 162 (76%) patients who had at least 12 weeks of follow-up after the first dose of cannabidiol were included in the safety and tolerability analysis, and 137 (64%) patients were included in the efficacy analysis. In the safety group, 33 (20%) patients had Dravet syndrome and 31 (19%) patients had Lennox-Gastaut syndrome. The remaining patients had intractable epilepsies of different causes and type. Adverse events were reported in 128 (79%) of the 162 patients within the safety group. Adverse events reported in more than 10% of patients were somnolence (n=41 [25%]), decreased appetite (n=31 [19%]), diarrhoea (n=31 [19%]), fatigue (n=21 [13%]), and convulsion (n

  18. Quality of Life in Childhood Epilepsy in pediatric patients enrolled in a prospective, open-label clinical study with cannabidiol.

    Science.gov (United States)

    Rosenberg, Evan C; Louik, Jay; Conway, Erin; Devinsky, Orrin; Friedman, Daniel

    2017-08-01

    Recent clinical trials indicate that cannabidiol (CBD) may reduce seizure frequency in pediatric patients with certain forms of treatment-resistant epilepsy. Many of these patients experience significant impairments in quality of life (QOL) in physical, mental, and social dimensions of health. In this study, we measured the caregiver-reported Quality of Life in Childhood Epilepsy (QOLCE) in a subset of patients enrolled in a prospective, open-label clinical study of CBD. Results from caregivers of 48 patients indicated an 8.2 ± 9.9-point improvement in overall patient QOLCE (p Epilepsy.

  19. A randomized, open-label, controlled trial of gabapentin and phenobarbital in the treatment of alcohol withdrawal.

    Science.gov (United States)

    Mariani, John J; Rosenthal, Richard N; Tross, Susan; Singh, Prameet; Anand, Om P

    2006-01-01

    Gabapentin was compared with phenobarbital for the treatment of alcohol withdrawal in a randomized, open-label, controlled trial in 27 inpatients. There were no significant differences in the proportion of treatment completers between treatment groups or the proportion of patients in each group requiring rescue medication for breakthrough signs and symptoms of alcohol withdrawal. There were no significant treatment differences in withdrawal symptoms or psychological distress, nor were there serious adverse events. These findings suggest that gabapentin may be as effective as phenobarbital in the treatment of alcohol withdrawal. Given gabapentin's favorable pharmacokinetic profile, further study of its effectiveness in treating alcohol withdrawal is warranted.

  20. Restrictive versus liberal blood transfusion for acute upper gastrointestinal bleeding (TRIGGER): a pragmatic, open-label, cluster randomised feasibility trial.

    Science.gov (United States)

    Jairath, Vipul; Kahan, Brennan C; Gray, Alasdair; Doré, Caroline J; Mora, Ana; James, Martin W; Stanley, Adrian J; Everett, Simon M; Bailey, Adam A; Dallal, Helen; Greenaway, John; Le Jeune, Ivan; Darwent, Melanie; Church, Nicholas; Reckless, Ian; Hodge, Renate; Dyer, Claire; Meredith, Sarah; Llewelyn, Charlotte; Palmer, Kelvin R; Logan, Richard F; Travis, Simon P; Walsh, Timothy S; Murphy, Michael F

    2015-07-11

    Transfusion thresholds for acute upper gastrointestinal bleeding are controversial. So far, only three small, underpowered studies and one single-centre trial have been done. Findings from the single-centre trial showed reduced mortality with restrictive red blood cell (RBC) transfusion. We aimed to assess whether a multicentre, cluster randomised trial is a feasible method to substantiate or refute this finding. In this pragmatic, open-label, cluster randomised feasibility trial, done in six university hospitals in the UK, we enrolled all patients aged 18 years or older with new presentations of acute upper gastrointestinal bleeding, irrespective of comorbidity, except for exsanguinating haemorrhage. We randomly assigned hospitals (1:1) with a computer-generated randomisation sequence (random permuted block size of 6, without stratification or matching) to either a restrictive (transfusion when haemoglobin concentration fell below 80 g/L) or liberal (transfusion when haemoglobin concentration fell below 100 g/L) RBC transfusion policy. Neither patients nor investigators were masked to treatment allocation. Feasibility outcomes were recruitment rate, protocol adherence, haemoglobin concentration, RBC exposure, selection bias, and information to guide design and economic evaluation of the phase 3 trial. Main exploratory clinical outcomes were further bleeding and mortality at day 28. We did analyses on all enrolled patients for whom an outcome was available. This trial is registered, ISRCTN85757829 and NCT02105532. Between Sept 3, 2012, and March 1, 2013, we enrolled 936 patients across six hospitals (403 patients in three hospitals with a restrictive policy and 533 patients in three hospitals with a liberal policy). Recruitment rate was significantly higher for the liberal than for the restrictive policy (62% vs 55%; p=0·04). Despite some baseline imbalances, Rockall and Blatchford risk scores were identical between policies. Protocol adherence was 96% (SD 10) in

  1. An open-label trial of a sumatriptan auto-injector for migraine in patients currently treated with subcutaneous sumatriptan.

    Science.gov (United States)

    Landy, Stephen H; Tepper, Stewart J; Wein, Theodore; Schweizer, Edward; Ramos, Elodie

    2013-01-01

    To assess the ability of patients, during an acute migraine attack, to successfully self-inject a single dose of sumatriptan using a novel sumatriptan auto-injector (Alsuma(®)), and to evaluate the safety, tolerability, and effectiveness of this sumatriptan auto-injector during an acute migraine attack. This sumatriptan auto-injector is a single-use system for the rapid subcutaneous delivery of 6 mg of sumatriptan succinate in the acute management of migraine pain. This auto-injector was developed to address the clinical need for an easy-to-use and rapid-to-administer system that did not require any assembly during the time of an ongoing attack. This was an open-label, phase 3 trial conducted at 10 sites in the USA. Male or female adults, ages 18-60 years old, were eligible for study entry if they met International Headache Society criteria for migraine with or without aura, with at least 2 attacks per month, and if they reported use of subcutaneous injectable sumatriptan on at least 2 occasions within the previous 2 months. During the onset of a migraine attack of moderate-to-severe intensity, patients were asked to administer a 6-mg subcutaneous dose of sumatriptan using the auto-injector. Patients returned to the study site within 72 hours of the migraine for the post-treatment assessment visit. A total of 63 patients met entry criteria and received a dose of study medication (the intent-to-treat sample). Sixty-one patients (96.8%) reported injection in the thigh, and 2 patients (3.2%) reported injection in the arm. On the patient questionnaire, 100% of patients (95% confidence interval [CI] 94.3-100%) "agreed" or "agreed strongly" that the written instructions for the auto-injector were clear and easy to follow (30.2% "agreed"; 69.8% "agreed strongly"); 95.2% of patients (95% CI 86.7-99.0%) found that the auto-injector was easy to use (36.5% "agreed"; 58.7% "agreed strongly"), and 65.1% of patients (95% CI 52.0-76.7%) stated that they preferred the new auto

  2. Prospective open-label study of add-on and monotherapy topiramate in civilians with chronic nonhallucinatory posttraumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Berlant Jeffrey L

    2004-08-01

    Full Text Available Abstract Background In order to confirm therapeutic effects of topiramate on posttraumatic stress disorder (PTSD observed in a prior study, a new prospective, open-label study was conducted to examine acute responses in chronic, nonhallucinatory PTSD. Methods Thirty-three consecutive newly recruited civilian adult outpatients (mean age 46 years, 85% female with DSM-IV-diagnosed chronic PTSD, excluding those with concurrent auditory or visual hallucinations, received topiramate either as monotherapy (n = 5 or augmentation (n = 28. The primary measure was a change in the PTSD Checklist-Civilian Version (PCL-C score from baseline to 4 weeks, with response defined as a ≥ 30% reduction of PTSD symptoms. Results For those taking the PCL-C at both baseline and week 4 (n = 30, total symptoms declined by 49% at week 4 (paired t-test, P Conclusions Promising open-label findings in a new sample converge with findings of a previous study. The use of topiramate for treatment of chronic PTSD, at least in civilians, warrants controlled clinical trials.

  3. A prospective, open-label study of low-dose total skin electron beam therapy in mycosis fungoides

    DEFF Research Database (Denmark)

    Kamstrup, Maria R; Specht, Lena; Skovgaard, Gunhild L

    2008-01-01

    PURPOSE: To determine the effect of low-dose (4 Gy) total skin electron beam therapy as a second-line treatment of Stage IB-II mycosis fungoides in a prospective, open-label study. METHODS AND MATERIALS: Ten patients (6 men, 4 women, average age 68.7 years [range, 55-82 years]) with histopatholog......PURPOSE: To determine the effect of low-dose (4 Gy) total skin electron beam therapy as a second-line treatment of Stage IB-II mycosis fungoides in a prospective, open-label study. METHODS AND MATERIALS: Ten patients (6 men, 4 women, average age 68.7 years [range, 55-82 years......]) with histopathologically confirmed mycosis fungoides T2-T4 N0-N1 M0 who did not achieve complete remission or relapsed within 4 months after treatment with psoralen plus ultraviolet-A were included. Treatment consisted of low-dose total skin electron beam therapy administered at a total skin dose of 4 Gy given in 4...... causes and did not complete treatment. Acute side effects included desquamation, xerosis, and erythema of the skin. No severe side effects were observed. CONCLUSION: Low-dose total skin electron beam therapy can induce complete and partial responses in Stage IB-II mycosis fungoides; however, the duration...

  4. Evaluation of safety and efficacy of zonisamide in adult patients with partial, generalized, and combined seizures: an open labeled, noncomparative, observational Indian study

    Directory of Open Access Journals (Sweden)

    Dash A

    2016-02-01

    Full Text Available Amitabh Dash,1 Sangeeta Ravat,2 Avathvadi Venkatesan Srinivasan,3 Ashutosh Shetty,4 Vivek Kumar,5 Renu Achtani,6 Vivek Narain Mathur,7 Boby Varkey Maramattom,8 Veeresh Bajpai,9 Nanjappa C Manjunath,10 Randhi Venkata Narayana,11 Suyog Mehta12 1Eisai Co. Ltd., 2Department of Neurology, Seth GS Medical College & KEM Hospital, Mumbai, 3Department of Neurology, Trinity Acute Care Hospital, Chennai, 4Department of Neurology, Criticare Multispeciality Hospital & Research Centre, Mumbai, 5Department of Neurology, Metro Multispeciality Hospital, Noida, 6Department of Neurology, Mata Chanan Devi Hospital, New Delhi, 7Department of Neurology, Vivekananda Hospital, Hyderabad, 8Department of Neurology, Lourdes Hospital, Kochi, 9Department of Neurology, Sai Neurology Clinic, Lucknow, 10Department of Neurology, Brain and Nerve Care, Bangalore, 11Department of Neurology, Seven Hills Hospital, Visakhapatnam, 12Department of Pharmacology & Therapeutics,Government Medical College, Solapur, India Abstract: A prospective, multicentric, noncomparative open-label observational study was conducted to evaluate the safety and efficacy zonisamide in Indian adult patients for the treatment of partial, generalized, or combined seizures. A total of 655 adult patients with partial, generalized, or combined seizures from 30 centers across India were recruited after initial screening. Patients received 100 mg zonisamide as initiating dose as monotherapy/adjunctive therapy for 24 weeks, with titration of 100 mg every 2 weeks if required. Adverse events, responder rates, and seizure freedom were observed every 4 weeks. Efficacy and safety were also assessed using Clinicians Global Assessment of Response to Therapy and Patients Global Assessment of Tolerability to Therapy, respectively. Follow-up was conducted for a period of 24 weeks after treatment initiation. A total of 655 patients were enrolled and received the treatment and 563 completed the evaluation phase. A total of 20

  5. Simplification to abacavir/lamivudine + atazanavir maintains viral suppression and improves bone and renal biomarkers in ASSURE, a randomized, open label, non-inferiority trial.

    Directory of Open Access Journals (Sweden)

    David A Wohl

    Full Text Available OBJECTIVE: Simplification of antiretroviral therapy in patients with suppressed viremia may minimize long-term adverse effects. The study's primary objective was to determine whether abacavir/lamivudine + atazanavir (ABC/3TC+ATV was virologically non-inferior to tenofovir/emtricitabine + atazanavir/ritonavir (TDF/FTC+ATV/r over 24 weeks in a population of virologically suppressed, HIV-1 infected patients. DESIGN: This open-label, multicenter, non-inferiority study enrolled antiretroviral experienced, HIV-infected adults currently receiving a regimen of TDF/FTC+ATV/r for ≥ 6 months with no history of virologic failure and whose HIV-1 RNA had been ≤ 75 copies/mL on 2 consecutive measurements including screening. Patients were randomized 1 ∶ 2 to continue current treatment or simplify to ABC/3TC+ATV. METHODS: The primary endpoint was the proportion of patients with HIV-RNA<50 copies/mL at Week 24 by the Time to Loss of Virologic Response (TLOVR algorithm. Secondary endpoints included alternative measures of efficacy, adverse events (AEs, and fasting lipids. Exploratory endpoints included inflammatory, coagulation, bone, and renal biomarkers. RESULTS: After 24 weeks, ABC/3TC+ATV (n = 199 was non-inferior to TDF/FTC+ATV/r (n = 97 by both the primary analysis (87% in both groups and all secondary efficacy analyses. Rates of grade 2-4 AEs were similar between the two groups (40% vs 37%, respectively, but an excess of hyperbilirubinemia made the rate of grade 3-4 laboratory abnormalities higher in the TDF/FTC+ATV/r group (30% compared with the ABC/3TC+ATV group (13%. Lipid levels were stable except for HDL cholesterol, which increased significantly in the ABC/3TC+ATV group. Bone and renal biomarkers improved significantly between baseline and Week 24 in patients taking ABC/3TC+ATV, and the difference between groups was significant at Week 24. No significant changes occurred in any inflammatory or coagulation biomarker within or between treatment

  6. Single-arm open-label study of Durolane (NASHA nonanimal hyaluronic acid for the treatment of osteoarthritis of the thumb

    Directory of Open Access Journals (Sweden)

    Velasco E

    2017-03-01

    Full Text Available Eloisa Velasco,1 Mª Victoria Ribera,2 Joan Pi3 1Department of Orthopedic Surgery, Hospital de Sant Joan Despí Moisés Broggi, Barcelona, Spain; 2Department of Anesthesiology, Vall d’Hebron University Hospital, Barcelona, Spain; 3Department of Orthopedics and Traumatology, Parc Taulí University Hospital, Sabadell, Barcelona, Spain Introduction: Osteoarthritis of the trapeziometacarpal (TMC joint of the thumb – also known as rhizarthrosis – is painful and has a significant impact on quality of life. Intra-articular injection of hyaluronic acid may potentially meet the need for effective, minimally invasive intervention in patients not responding adequately to initial treatment. We aimed to confirm the safety and effectiveness of viscosupplementation with Durolane (NASHA nonanimal hyaluronic acid in rhizarthrosis.Patients and methods: This was a prospective, single-arm, multicenter, open-label study with a 6-month follow-up period. Eligible patients had Eaton–Littler grade II–III rhizarthrosis in one TMC joint with pain and visual analog scale (VAS pain score ≥4 (scale: 0–10. A single injection of NASHA was administered to the affected TMC joint. The primary effectiveness variable was change from baseline in VAS pain score.Results: Thirty-five patients (mean age 60.8 years; 85.7% female received NASHA and completed the study. The least-squares mean change from baseline in VAS pain score over 6 months was –2.00, a reduction of 27.8% (p<0.001. The reduction in pain exceeded 25% as early as month 1 (26.5%, and gradual improvement was observed throughout the 6-month follow-up period. Secondary effectiveness parameters included QuickDASH (shortened version of Disabilities of the Arm, Shoulder, and Hand [DASH], Kapandji thumb opposition test, radial abduction, metacarpophalangeal (MCP joint flexion, and pinch (clamp strength. Most of these measurements showed statistically significant improvements from baseline over 6 months. Five

  7. An open-label, flexible-dose study of paliperidone extended-release in Chinese patients with first-onset psychosis

    Directory of Open Access Journals (Sweden)

    Si TM

    2015-01-01

    Full Text Available TianMei Si,1 QingRong Tan,2 KeRang Zhang,3 Yang Wang,4 Qing Rui4 1Peking University Institute of Mental health, Key Laboratory of Mental Health, Ministry of Health (Peking University, Beijing, 2Fourth Military Medical University, First Hospital, Xi’an, 3Shanxi Medical University, First Hospital, Shanxi, 4Janssen Research and Development, Beijing, People’s Republic of China Background: Antipsychotic medications facilitate the improvement of psychotic symptoms in patients with first-episode psychosis. Paliperidone extended-release (pali-ER, an atypical anti­psychotic, was assessed for efficacy and safety in Chinese patients with first-episode psychosis. Methods: In this 8-week, open-label, single-arm, multicenter study, patients with first-episode psychosis (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and a Positive and Negative Syndrome Scale (PANSS total score ≥70 were treated with flexible-dose pali-ER tablets (3–12 mg/day. The primary efficacy endpoint was the percentage of patients with an increase of ≥8 points in Personal and Social Performance (PSP score from baseline to day 56 (8 weeks. Secondary endpoints included reduction in PANSS total score, improvement in Clinical Global Impression-Severity score, PSP score, Subjective Well-being under Neuroleptics Scale score, and relationship between duration of untreated psychosis and PANSS or PSP. Incidences of treatment-emergent adverse events were used to evaluate safety.Results: Overall, 283 of 294 patients (96% achieved a ≥8-point increase in PSP (primary endpoint, analysis set. For the secondary efficacy endpoints, 284/306 patients (93% had a ≥30% reduction in PANSS total score; 266/306 patients (87% achieved a ≤3 Clinical Global Impression-Severity scale score, and 218/294 patients (74% had a PSP score ≥71. The Subjective Well-being under Neuroleptics Scale score was improved from a baseline mean of 72.7 to 94.7 at endpoint. There was a

  8. Nitrous oxide-oxygen mixture during care of bedsores and painful ulcers in the elderly: a randomized, crossover, open-label pilot study.

    Science.gov (United States)

    Paris, Adeline; Horvath, Rémi; Basset, Pierre; Thiery, Stéphane; Couturier, Pascal; Franco, Alain; Bosson, Jean-Luc

    2008-02-01

    Bedsore and ulcer care can often be painful and no standardized analgesic method exists today for pain relief during treatment in adults and the elderly. To evaluate the analgesic efficacy of a nitrous oxide-oxygen mixture vs. morphine during painful bedsore and ulcer care in adult and elderly patients, we conducted a randomized, crossover, multicenter, prospective, open-label, pilot study. Thirty-four inpatients, aged 53-96 years (median 84 years), were recruited in Grenoble University Hospital, Annecy Hospital and Chambéry Hospital, France, from January to June 2001. Each of the 34 patients received morphine (M), nitrous oxide-oxygen mixture (E), or morphine+nitrous oxide-oxygen mixture (ME) during painful care in a crossover protocol. Treatments were changed every two days and the study duration was six days. Analgesia was evaluated before and after each care session using a behavioral scale to evaluate pain in noncommunicating adults (ECPA), a visual analog scale (VAS), a global hetero-evaluation scale (GHES), and the DOLOPLUS-2 scale. There was a significant overall difference (P<0.01) among the three treatments. On the ECPA, the average difference after and before care was +5.2+/-8.6 (M), -0.3+/-8 (E), and -0.6+/-7.4 (ME), respectively. There was a significant difference between M and E, and M and ME (each P<0.01). No difference was found between E and ME (P=0.97). There were similar significant differences in the GHES and DOLOPLUS-2 scales (all tests P<0.01). Post hoc comparisons showed a significant difference (P<0.01) between M and E, and between M and ME without any additional effect for M+E. No differences were found with regard to safety or tolerability. This pilot study demonstrates the superiority of nitrous oxide-oxygen mixture over morphine for analgesia. This experience suggests that this mixture has ease of use, rapid effect, and limited contraindications when used during painful bedsore and ulcer care in elderly patients. Furthermore, it is well

  9. Clinical effectiveness and safety of escitalopram and desvenlafaxine in patients of depression with anxiety: a randomized, open-label controlled trial.

    Science.gov (United States)

    Maity, Nabakumar; Ghosal, Malay Kumar; Gupta, Anupam; Sil, Amrita; Chakraborty, Sushmita; Chatterjee, Suparna

    2014-01-01

    Selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) are effective in treating anxiety disorders associated with major depressive disorder (MDD). This randomized, controlled, parallel-group, open-label, phase 4 trial (CTRI/2012/08/002895) was undertaken to compare the effectiveness and safety of desvenlafaxine versus escitalopram, a standard antidepressant. Effectiveness was assessed using the Hamilton Depression Rating Scale (HAM-D17) and Hamilton Anxiety Rating Scale (HAM-A). Response to treatment was assessed by ≥50% decrease of baseline scores (responder rate). Safety and tolerability was evaluated by changes in routine laboratory parameters, vital signs, and adverse events reported by the subject and/or observed by the clinician. Responder rates for both HAM-A and HAM-D scores at 8 weeks were better in the escitalopram group compared to the desvenlafaxine group (HAM-A 76.92% vs. 71.05%; HAM-D 79.48% vs 73.68%) but the differences were not statistically significant (P = 0.59 and P = 0.61). Within group changes of both scores, from baseline to subsequent visits in both treatment arms were statistically significant (P desvenlafaxine was comparable to escitalopram, but escitalopram was better tolerated.

  10. An Open-Label Trial of 12-Week Simeprevir plus Peginterferon/Ribavirin (PR in Treatment-Naive Patients with Hepatitis C Virus (HCV Genotype 1 (GT1.

    Directory of Open Access Journals (Sweden)

    Tarik Asselah

    Full Text Available Shortening duration of peginterferon-based HCV treatment reduces associated burden for patients. Primary objectives of this study were to assess the efficacy against the minimally acceptable response rate 12 weeks post-treatment (SVR12 and safety of simeprevir plus PR in treatment-naïve HCV GT1 patients treated for 12 weeks. Additional objectives included the investigation of potential associations of rapid viral response and baseline factors with SVR12.In this Phase III, open-label study in treatment-naïve HCV GT1 patients with F0-F2 fibrosis, patients with HCV-RNA 12-week regimen.Overall SVR12 rate (66% was below the target of 80%, indicating that shortening of treatment with simeprevir plus PR to 12 weeks based on very early response is not effective. However, baseline factors associated with higher SVR12 rates were identified. Therefore, while Week 2 response alone is insufficient to predict efficacy, GT1 patients with favourable baseline factors may benefit from a shortened simeprevir plus PR regimen.ClinicalTrials.gov NCT01846832.

  11. Infliximab-induced autoantibodies: a multicenter study.

    Science.gov (United States)

    Vaz, João Luiz Pereira; Fernandes, Vander; Nogueira, Felipe; Arnóbio, Adriano; Levy, Roger A

    2016-02-01

    The purpose of this study was to assess autoantibody incidence in patients treated with infliximab for various diseases, and the development of autoimmune diseases using a multicenter, longitudinal, open-label, phase IV observational study. All patients received anti-tumor necrosis factor (anti-TNF) according to local treatment guidelines. The autoantibodies assessed before and after infliximab treatment were ANA, anti-Sm, anti-dsDNA, anticardiolipin IgM/IgG, anti-Scl70, anti-centromere B, anti-chromatin, anti-ribosomal P, anti-Sm-RNP, anti-RNP A, anti-RNP 68 kD, anti-La/SSB, anti-Ro/SSA 52 kD and 60 kD, and anti-Jo1. ANA was determined by indirect immunofluorescence on HEp-2 cells (INOVA); the remaining was assessed using BioPlexTM 2200. The Fisher exact test, Wilcoxon test, and the McNemar were used when appropriate.Two hundred eighty-six patients were included (139 with rheumatoid arthritis, 77 with ankylosing spondylitis, 29 with inflammatory bowel disease, 27 with psoriatic arthritis, and 14 with psoriasis), 167 females and 119 males, with mean age of 46.3 years. Subjects received at least five infusions of infliximab (6-month treatment). A significant difference was observed in antinuclear antibody (ANA) detection between samplings (p = 0.001). Among patients that had ANA before treatment (n = 92), six became ANA-negative, 48 had increased titers, 29 maintained, and nine decreased titers after treatment; a total of 186 patients had a positive ANA after treatment. Fine speckled nuclear pattern was most commonly observed (both before and after infliximab treatment). The number of patients with anti-dsDNA had a statistically significant increase (p = 0.003). No significant differences were noted for anticardiolipin and the remaining autoantibodies tested. Among the 286 patients included in the study, only one (0.35 %) showed clinical signs of drug-induced lupus, presenting elevated ANA and anti-dsDNA titers that normalized once treatment was

  12. Comparison of 1.0 M gadobutrol and 0.5 M gadopentate dimeglumine-enhanced MRI in 471 patients with known or suspected renal lesions: Results of a multicenter, single-blind, interindividual, randomized clinical phase III trial

    NARCIS (Netherlands)

    B. Tombach (Bernd); K. Bohndorf (Klaus); W. Brodtrager (Wolfgang); C.D. Claussen (Claus); C. Düber (Christoph); M. Galanski (Michael); E. Grabbe (Eckhardt); G. Gortenuti (Giacomo); M. Kuhn (Michael); W. Gross-Fengels (Walter); R. Hammerstingl (Renate); B. Happel (Brigitte); G. Heinz-Peer (Gertraud); G. Jung (Gregor); T. Kittner (Thomas); R. Lagalla; P. Lengsfeld (Philipp); R. Loose (Reinhard); R.H.G. Oyen (Raymond); P. Pavlica (Pietro); C. Pering (Christiane); R. Pozzi Mucelli (Roberto Silvio); T. Persigehl (Thorsten); P. Reimer (Peter); N.S. Renken (Nomdo); G.M. Richter (Götz); E.J. Rummeny (Ernst); F. Schäfer (Fritz); M. Szczerbo-Trojanowska (Malgorzata); A. Urbanik (Andrzej); T.J. Vogl (Thomas); P. Hajek (Paul)

    2008-01-01

    textabstractThe purpose of this phase III clinical trial was to compare two different extracellular contrast agents, 1.0 M gadobutrol and 0.5 M gadopentate dimeglumine, for magnetic resonance imaging (MRI) in patients with known or suspected focal renal lesions. Using a multicenter, single-blind, in

  13. Rifaximin Is Effective for the Treatment of Clostridium difficile—Associated Diarrhea: Results of an Open-Label Pilot Study

    Directory of Open Access Journals (Sweden)

    David T. Rubin

    2011-01-01

    Full Text Available Objectives. This open-label trial assessed the efficacy and safety of rifaximin as first-line therapy in hospitalized patients with Clostridium difficile-associated diarrhea (CDAD. Methods. We enrolled thirteen patients who had a confirmed diagnosis of CDAD characterized by ≥3 unformed stools/day and positive C. difficile toxin assay. Those patients received rifaximin 400 mg three times daily for 10 days. Resolution of symptoms, repeat assay 10 days after treatment, and followup for recurrence were assessed. Results. Eight patients completed the study, and all reported symptom resolution during treatment. Mean time to last unformed stool was 132 h ± 42.5 h. Seven patients had no relapse by week 2 and in longer followup (median 162 days. One patient had recurrent CDAD during a repeat hospitalization. Conclusions. Rifaximin was effective and safe as first-line treatment for CDAD and did not result in recurrence in most patients.

  14. The effects of amisulpride on five dimensions of psychopathology in patients with schizophrenia: a prospective open- label study

    Directory of Open Access Journals (Sweden)

    Fresan Ana

    2005-05-01

    Full Text Available Abstract Background The efficacy of antipsychotics can be evaluated using the dimensional models of schizophrenic symptoms. The D2/D3-selective antagonist amisulpride has shown similar efficacy and tolerability to other atypical antipsychotics. The aim of the present study was to determine the efficacy of amisulpride on the dimensional model of schizophrenic symptoms and tolerability in latin schizophrenic patients. Method Eighty schizophrenic patients were enrolled and 70 completed a prospective open-label 3-month study with amisulpride. The schizophrenic symptoms, psychosocial functioning and side-effects were evaluated with standardized scales. Results The patients showed significant improvement in the five dimensions evaluated. Amisulpride (median final dose 357.1 mg/d was well-tolerated without treatment-emergent extrapyramidal side-effects. Conclusion Amisulpride showed efficacy on different psychopathological dimensions and was well tolerated, leading to consider this drug a first line choice for the treatment of schizophrenia.

  15. Long-term safety and tolerability of open-label aripiprazole augmentation of antidepressant therapy in major depressive disorder

    Directory of Open Access Journals (Sweden)

    Berman R

    2011-05-01

    Full Text Available Robert M Berman1, Michael E Thase2, Madhukar H Trivedi3, James A Hazel4, Sabrina Vogel Marler5, Robert D McQuade6, William Carson7, Ross A Baker8, Ronald N Marcus91Neuroscience Global Clinical Research Bristol-Myers Squibb, Wallingford, CT, USA; 2Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; 3Division of Mood Disorders Research Program and Clinic, University of Texas Southwestern Medical School, Dallas, TX, USA; 4Neuroscience Global Clinical Research, Bristol-Myers Squibb, Wallingford, CT, USA; 5Global Biometric Sciences, Bristol-Myers Squibb, Wallingford, CT, USA; 6Global Medical Affairs at Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, NJ, USA; 7Global Clinical Development, Otsuka Pharmaceutical Development and Commercialization Inc, Princeton, NJ, USA; 8Neuroscience Medical Strategy, Bristol-Myers Squibb Company, Plainsboro, NJ, USA; 9Neuroscience Global Clinical Research, Bristol-Myers Squibb, Wallingford, CT, USABackground: Effective management of major depressive disorder often includes the long-term use of multiple medications, and the longer-term utility and safety of adjunctive aripiprazole has not been evaluated in a controlled setting.Patients and methods: Patients (n = 706 completing one of two 14-week double-blind studies of aripiprazole augmentation, as well as de novo patients (n = 296 nonresponsive to current antidepressant therapy, were enrolled in this open-label study. Patients received open-label aripiprazole for up to 52 weeks.Results: Open-label treatment was completed by 323 patients (32.2%. At endpoint (n = 987, the mean dose of aripiprazole was 10.1 mg/day. Common (>15% of patients spontaneously reported adverse events were akathisia (26.2%, fatigue (18.0%, and weight gain (17.1%. The incidence of serious adverse events was 4.0%. Four spontaneous reports of possible tardive dyskinesia were submitted (0.4%; all resolved within 45 days of drug

  16. Escitalopram in the treatment of patients with schizophrenia and obsessive-compulsive disorder: an open-label, prospective study.

    Science.gov (United States)

    Stryjer, Rafael; Dambinsky, Yael; Timinsky, Igor; Green, Tamar; Kotler, Moshe; Weizman, Abraham; Spivak, Baruch

    2013-03-01

    The current data suggest that up to 50% of patients with schizophrenia have obsessive-compulsive (OC) symptoms coexisting with psychosis and between 7.8 and 46% of schizophrenia patients also have full-blown obsessive-compulsive disorder (OCD). The aim of this study was to examine the efficacy of the most selective serotonin reuptake inhibitor escitalopram in the management of OCD in schizophrenia patients. The study was an open-label prospective trial of 12 weeks' duration in which escitalopram at a dose of up to 20 mg/day was added to the existing antipsychotic drug regimen in schizophrenia patients with OCD. Fifteen patients (10 men/five women) with the diagnosis of schizophrenia and OCD were recruited for the study (mean age: 39±14, range 21-61 years) and received escitalopram according to the study design. A significant improvement was observed in the total Yale Brown Obsessive-Compulsive Scale (Y-BOCS) scores and in the scores of both the Y-BOCS-Obsession and the Y-BOCS-Compulsion subscale at the end point. In addition, a significant improvement was observed in the total scores of the Positive and Negative Syndrome Scale and particularly in scores of anxiety, tension, depression, and preoccupation items. No adverse effects of escitalopram were reported by patients during the trial. In our prospective 12-week open-label study, escitalopram 20 mg/day was well tolerated and improved OC symptoms in schizophrenia patients. Our preliminary results are encouraging and a double-blind randomized study is required to confirm our results.

  17. Long-term safety, tolerability and efficacy of fesoterodine in subjects with overactive bladder symptoms stratified by age: pooled analysis of two open-label extension studies.

    Science.gov (United States)

    Sand, Peter K; Heesakkers, John; Kraus, Stephen R; Carlsson, Martin; Guan, Zhonghong; Berriman, Sandra

    2012-02-01

    Previous work has demonstrated the efficacy and safety of fesoterodine in older and younger subjects with overactive bladder (OAB) symptoms. The effect of long-term fesoterodine treatment in different age groups has not been assessed. The aim was to determine the impact of age on the safety, tolerability and efficacy of long-term treatment with fesoterodine 8 mg in subjects with OAB syndrome. This was a pooled analysis of two identically designed open-label extensions of 12-week, randomized, double-blind, placebo-controlled studies. The setting was urology and general practice offices. Subjects who participated in the 12-week, double-blind studies and opted to continue long-term, open-label treatment with fesoterodine were included. Subjects were initiated on fesoterodine 8 mg/day at open-label baseline. After 1 month, subjects could elect dose reduction to 4 mg/day and subsequent re-escalation to 8 mg; each was permitted once annually. Maximal duration of open-label treatment ranged from 24 to 36 months. Discontinuations, subject-reported treatment tolerance, and efficacy (3-day diaries) were assessed at open-label baseline and months 1, 4, 8, 12 and 24. A total of 890 subjects were treated (age fesoterodine 8 mg throughout treatment; this rate was highest among subjects aged ≥75 years (age fesoterodine 8 mg at each visit after open-label baseline up to 36 months. No new or unexpected safety signals were observed in any age group. Most subjects reported 'good' or 'excellent' treatment tolerance throughout the study (age fesoterodine (administered primarily as 8 mg) was well tolerated and associated with sustained improvements in OAB symptoms, irrespective of age.

  18. Efficacy, adherence and tolerability of once daily tenofovir DF-containing antiretroviral therapy in former injecting drug users with HIV-1 receiving opiate treatment: results of a 48-week open-label study

    Directory of Open Access Journals (Sweden)

    Esser S

    2011-10-01

    Full Text Available Abstract Objective To assess efficacy, adherence and tolerability of once daily antiretroviral therapy containing tenofovir disoproxil fumarate (DF 300 mg in HIV-1-infected former injecting drug users receiving opiate treatment (IVDU. Methods European, 48-week, open-label, single-arm, multicenter study. Patients were either antiretroviral therapy-naïve, restarting therapy after treatment discontinuation without prior virological failure or switching from existing stable treatment. Results Sixty-seven patients were enrolled in the study and 41 patients completed treatment. In the primary analysis (intent-to-treat missing = failure at week 48, 34% of patients (23/67; 95% CI: 23%-47% had plasma HIV-1 RNA 3. Although self-reported adherence appeared high, there were high levels of missing data and adherence results should be treated with caution. No new safety issues were identified. Conclusions Levels of missing data were high in this difficult-to-treat population, but potent antiretroviral suppression was achieved in a substantial proportion of HIV-infected IVDU-patients.

  19. Open-label evaluation of a novel skin brightening system containing 0.01% decapeptide-12 in combination with 20% buffered glycolic acid for the treatment of mild to moderate facial melasma.

    Science.gov (United States)

    Ramírez, Sandra P; Carvajal, Alfonso C; Salazar, Juan C; Arroyave, Gladys; Flórez, Ana M; Echeverry, Hector F

    2013-06-01

    Melasma is a cutaneous disorder that primarily affects females of Hispanic and Asian descent. Previous studies have shown that use of a brightening system comprised of 0.01% decapeptide-12 cream, an antioxidant cleanser, a 20% buffered glycolic acid lotion, and a broad spectrum SPF 30 sunscreen yields good clearance of mild-to-moderate melasma in Caucasian and Asian volunteers. The present open-label, prospective, and multicenter study sought to determine the tolerability and efficacy of the above-mentioned brightening system on mild-to-moderate melasma in 33 Hispanic females over 16 weeks. Clinical measures included self-assessment of tolerability, clinical grading, determination of Melasma Area and Severity Index (MASI) scores, and standardized clinical photography. Results showed that the system was well tolerated with no adverse events reported. Mean decreases of 36%, 46%, 54%, and 60% in MASI scores were observed at weeks 4, 8, 12, and 16, respectively, which were further corroborated by standardized photography showing visible reduction in the appearance of melasma. Results suggest that the brightening system consisting of 0.01% decapeptide-12 cream, an antioxidant cleanser, 20% buffered glycolic acid lotion, and broad spectrum SPF 30 sunscreen is safe and efficacious for the treatment of mild-to-moderate melasma in Hispanic females.

  20. Long-term safety, tolerability and efficacy of flexible-dose fesoterodine in elderly patients with overactive bladder: open-label extension of the SOFIA trial.

    Science.gov (United States)

    Wagg, Adrian; Khullar, Vik; Michel, Martin C; Oelke, Matthias; Darekar, Amanda; Bitoun, Caty Ebel

    2014-01-01

    To assess the long-term safety, tolerability, and efficacy of flexible-dose fesoterodine in elderly patients with OAB. Patients aged ≥65 years who completed a 12-week, randomized, double-blind, placebo-controlled trial were eligible for the 12-week, open-label (OL) extension phase. Patients who received double-blind placebo started on fesoterodine 4 mg and could increase to 8 mg after 4 or 8 weeks of OL treatment, while fesoterodine-treated patients continued on their double-blind dose; only one dose escalation or de-escalation was permitted. Discontinuations and adverse events (AEs) were monitored, and patients completed 3-day bladder diaries and patient-reported outcomes at the beginning and end of the 12-week OL phase. Six hundred fifty-four patients entered the 12-week OL extension (mean age 72 years; 52% women). AEs were reported by 30.7% and 48.1% of patients who had received double-blind fesoterodine and placebo, respectively; 1.9% and 9.4%, discontinued due to AEs, respectively. Patients who received double-blind fesoterodine maintained their efficacy response. After 12 weeks of OL treatment, efficacy outcomes in patients who received double-blind placebo were similar to those who had received double-blind fesoterodine. On average, the efficacy response was maintained for the duration of the study. Fesoterodine was well tolerated and improvements in OAB symptoms and quality of life measures were not diminished with longer-term treatment of patients aged ≥65 years. © 2013 Wiley Periodicals, Inc.

  1. Intravenous carbamazepine as short-term replacement therapy for oral carbamazepine in adults with epilepsy: Pooled tolerability results from two open-label trials.

    Science.gov (United States)

    Lee, Deborah; Kalu, Uwa; Halford, Jonathan J; Biton, Victor; Cloyd, James; Klein, Pavel; Bekersky, Ihor; Peng, Guangbin; Dheerendra, Suresh; Tolbert, Dwain

    2015-06-01

    To report tolerability findings and maintenance of seizure control from a pooled analysis of phase I open-label trial OV-1015 (NCT01079351) and phase III study 13181A (NCT01128959). Patients receiving a stable oral dosage of carbamazepine were switched to an intravenous (IV) carbamazepine formulation solubilized in a cyclodextrin matrix (at a 70% dosage conversion) for either a 15- or a 30-min infusion every 6 h for up to 7 days and then switched back. A subset of patients who tolerated 15-min infusions also received 2- to 5-min (rapid) infusions. Assessments included physical and laboratory evaluations, electrocardiography (ECG) studies, as well as adverse event (AE) monitoring for tolerability. Convulsion/seizure AE terms and data from seizure diaries were used as proxies for the assessment of consistency of seizure control between formulations. Of the 203 patients exposed to IV carbamazepine (30 min, n = 43; 15 min, n = 160), 113 received 149 rapid infusions. During infusion, the most commonly reported AEs (≥ 5%) were dizziness (19%), somnolence (6%), headache (6%), and blurred vision (5%). IV carbamazepine was not associated with clinically relevant cardiac AEs. The tolerability profile appeared similar between patients who received oral and IV carbamazepine. IV carbamazepine administered as multiple 30- or 15-min infusions every 6 h, and as a single rapid infusion, was well tolerated as a short-term replacement in adults with epilepsy receiving stable dosages of oral carbamazepine. Infusion site reactions, which were generally mild, were the only unique AEs identified; seizure control was generally unchanged when patients were switching between formulations. © 2015 Lundbeck LLC. Epilepsia published by Wiley Periodicals Inc. on behalf of International League Against Epilepsy.

  2. Effect of minoxidil topical foam on frontotemporal and vertex androgenetic alopecia in men: a 104-week open-label clinical trial.

    Science.gov (United States)

    Kanti, V; Hillmann, K; Kottner, J; Stroux, A; Canfield, D; Blume-Peytavi, U

    2016-07-01

    Topical minoxidil formulations have been shown to be effective in treating androgenetic alopecia (AGA) for 12 months. Efficacy and safety in both frontotemporal and vertex regions over longer application periods have not been studied so far. To evaluate the effect of 5% minoxidil topical foam (5% MTF) in the frontotemporal and vertex areas in patients with moderate AGA over 104 weeks. An 80-week, open-label extension phase was performed, following a 24-week randomized, double-blind, placebo-controlled study in men with AGA grade IIIvertex to VI. Group 1 (n = 22) received ongoing 5% MTF for 104 weeks, Group 2 (n = 23) received placebo topical foam (plaTF) until week 24, followed by 5% MTF until week 104 during the extension phase. Frontotemporal and vertex target area non-vellus hair counts (f-TAHC, v-TAHC) and cumulative hair width (f-TAHW, v-TAHW) were assessed at baseline and at weeks 24, 52, 76 and 104. In Group 1, f-TAHW and f-TAHC showed a statistically significant increase from baseline to week 52 and week 76, respectively, returning to values comparable to baseline at week 104. No significant differences were found between baseline and week 104 in v-TAHC in Group 1 as well as f-TAHC, v-TAHC, f-TAHW and v-TAHW values in Group 2. 5% MTF is effective in stabilizing hair density, hair width and scalp coverage in both frontotemporal and vertex areas over an application period of 104 weeks, while showing a good safety and tolerability profile with a low rate of irritant contact dermatitis. © 2015 European Academy of Dermatology and Venereology.

  3. Tolerability and safety of souvenaid in patients with mild Alzheimer's disease: results of multi-center, 24-week, open-label extension study

    NARCIS (Netherlands)

    Olde Rikkert, M.G.M.; Verhey, F.R.J.; Blesa, R.; Arnim, C.A. von; Bongers, A.; Harrison, J.; Sijben, J.; Scarpini, E.; Vandewoude, M.F.; Vellas, B.; Witkamp, R.; Kamphuis, P.J.; Scheltens, P.

    2015-01-01

    BACKGROUND: The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to improve synapse formation and function in patients with Alzheimer's disease (AD). Two double-blind randomized controlled trials (RCT) with Souvenaid of 12 and 24 week duration (Souve

  4. B cell activation biomarkers as predictive factors for the response to rituximab in rheumatoid arthritis: a six-month, national, multicenter, open-label study.

    Science.gov (United States)

    Sellam, Jérémie; Hendel-Chavez, Houria; Rouanet, Stéphanie; Abbed, Karim; Combe, Bernard; Le Loët, Xavier; Tebib, Jacques; Sibilia, Jean; Taoufik, Yassine; Dougados, Maxime; Mariette, Xavier

    2011-04-01

    To examine whether serum B cell markers can predict response to rituximab, a B cell-depleting monoclonal antibody, in patients with refractory rheumatoid arthritis (RA). This rituximab re-treatment dose study (SMART [eSsai MAbthera sur la dose de Re-Traitement]) involved 208 patients with refractory RA. Serum markers of B cell activation (anti-cyclic citrullinated peptide [anti-CCP] antibodies, rheumatoid factor [RF], serum IgG, IgA, and IgM levels, serum κ and λ free light chains, and serum BAFF) were assessed before the first rituximab cycle (1,000 mg on days 1 and 15). Univariate and multivariate analyses were performed to identify factors associated with a European League Against Rheumatism (EULAR) response at 24 weeks. There were 149 responders (72%). Two baseline factors were associated with a EULAR response at 24 weeks in multivariate analysis: the presence of anti-CCP antibodies or RF (odds ratio 3.5 [95% confidence interval 1.6-7.6]) and a serum IgG concentration above normal (odds ratio 2.11 [95% confidence interval 1.02-4.33]), with synergy between them (odds ratio 6.0 [95% confidence interval 2.2-16.2]). The presence of RF or anti-CCP antibodies and elevated IgG are 2 simple biomarkers that can be used routinely before therapy to predict response to rituximab in patients with refractory RA. Copyright © 2011 by the American College of Rheumatology.

  5. Two-year outcomes in thoracic transplant recipients after conversion to everolimus with reduced calcineurin inhibitor within a multicenter, open-label, randomized trial

    DEFF Research Database (Denmark)

    Gullestad, Lars; Mortensen, Svend-Aage; Eiskjær, Hans;

    2010-01-01

    Use of the mammalian target of rapamycin inhibitor everolimus with an accompanying reduction in calcineurin inhibitor (CNI) exposure has shown promise in preserving renal function in maintenance thoracic transplant patients, but robust, long-term data are required.......Use of the mammalian target of rapamycin inhibitor everolimus with an accompanying reduction in calcineurin inhibitor (CNI) exposure has shown promise in preserving renal function in maintenance thoracic transplant patients, but robust, long-term data are required....

  6. A multicenter randomized open-label study of rituximab plus rhTPO vs rituximab in corticosteroid-resistant or relapsed ITP.

    Science.gov (United States)

    Zhou, Hai; Xu, Miao; Qin, Ping; Zhang, Hai-yan; Yuan, Cheng-lu; Zhao, Hong-guo; Cui, Zhong-guang; Meng, Yue-sheng; Wang, Lei; Zhou, Fang; Wang, Xin; Li, Da-qi; Bi, Ke-hong; Zhu, Chuan-sheng; Guo, Cheng-shan; Chu, Xiao-xia; Wu, Qing-chao; Liu, Xin-guang; Dong, Xiao-yuan; Li, Jie; Peng, Jun; Hou, Ming

    2015-03-05

    This study aimed to compare the efficacy and safety of rituximab (RTX) plus recombinant human thrombopoietin (rhTPO) with RTX alone in patients with immune thrombocytopenia (ITP) who had failed to respond to corticosteroids or relapsed. Recruited patients were randomized at a ratio of 2:1 into 2 groups: the combination group (RTX + rhTPO, n = 77) and the monotherapy group (RTX, n = 38). Overall response was achieved in 79.2% of patients in the combination group vs 71.1% in the monotherapy group (P = .36), and the complete response (CR) rate was 45.4% in the combination group compared with 23.7% in the monotherapy group (P = .026). The combination group had significantly shorter time to response (TTR; median and range, 7 and 4-28 days) compared with the monotherapy group (28 and 4-90 days) (P rhTPO significantly increased the CR rate and shortened TTR compared with RTX monotherapy in the treatment of corticosteroid-resistant or relapsed ITP but failed to show a beneficial effect on the long-lasting response. This study is registered at www.clinicaltrials.gov as #NCT01525836.

  7. Assessment of the efficacy and tolerability of 2 formulations of atorvastatin in Korean adults with hypercholesterolemia: a multicenter, prospective, open-label, randomized trial.

    Science.gov (United States)

    Kim, Sang-Hyun; Seo, Myung-Ki; Yoon, Myeong-Ho; Choi, Dong-Hoon; Hong, Taek-Jong; Kim, Hyo-Soo

    2013-01-01

    A manufacturer of atorvastatin is seeking marketing approval in Korea of a generic product for adult patients with primary hypercholesterolemia. The objective of this study was to compare the efficacy and tolerability of a new generic formulation of atorvastatin (test) with those of an original formulation of atorvastatin (reference) to satisfy regulatory requirements for marketing of the generic product in Korea. Patients enrolled were aged 20 to 79 years with documented primary hypercholesterolemia who did not respond adequately to therapeutic lifestyle changes and with a LDL-C level >100 mg/dL from a high-risk group of coronary artery disease patients. Eligible patients were randomized to receive 1 of the 2 formulations of atorvastatin 20 mg per day for 8 weeks. The primary end point was the percent change in LDL-C level from baseline to week 8. Secondary end points included the percent change in total cholesterol, triglycerides, HDL-C level, apolipoprotein B:apolipoprotein A-I ratio, LDL:HDL ratio, LDL-C particle size, high-sensitivity C-reactive protein from baseline to week 8, and achievement rate of the LDL-C goal. A total of 298 patients (141 men and 157 women; 149 patients in each group; mean [SD] age, 62.4 [9.2] in the test group vs 60.3 [8.9] years in the reference group) were included. LDL-C levels were significantly decreased from baseline to week 8 in both groups, and there was no significant difference in the percent change in LDL-C level between groups (-44.0% [17.2%] in the test group, -45.4% [16.9%] in the reference group; P = 0.49). The between-group differences in the percent changes in total cholesterol and triglyceride levels were not statistically significant. In addition, there was no significant difference between the 2 groups in percent changes in HDL-C, apolipoprotein B:apolipoprotein A-I ratio, LDL-C:HDL-C ratio, LDL-C particle size, high-sensitivity C-reactive protein, and the achievement rate of the LDL-C goal. Two (1.3%) patients in the reference group (N = 150) experienced treatment-related serious adverse events (AEs): toxic hepatitis and aggravation of chest pain. Common AEs were cough (4.1%), myalgia (2.1%), and indigestion (1.4%) in the test formulation group and cough (5.3%), creatine kinase elevation (2.7%), and edema (0.7%) in the reference formulation group; however, the differences in overall prevalence of AEs between the 2 treatment groups was not significant (P = 0.88). There were no significant differences observed in the efficacy and tolerability between the test and reference formulations of atorvastatin in these Korean adult patients with primary hypercholesterolemia. Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.

  8. A 36 months, Danish multicenter, open-label, study to investigate adherence, treatment satisfaction, motivation and quality of life in RRMS patients treated with fingolimod

    DEFF Research Database (Denmark)

    Schreiber, Karen; Kant, Matthias; Pfleger, Claudia

    of patient dissatisfaction with the treatment or low motivation to treatment. The unpredictable nature of relapses in RRMS may also lead to perceived lack of efficacy and decreased adherence. Objectives The objective of this study was to investigate adherence to fingolimod therapy and to evaluate to what...... dissatisfaction with the treatment or low motivation to treatment. The unpredictable nature of relapses in RRMS may also lead to perceived lack of efficacy and decreased adherence. Objectives The objective of this study was to investigate adherence to fingolimod therapy and to evaluate to what extend treatment...... to treatment in Multiple Sclerosis has shown to lead to poor health outcomes (ref. 1). Patients outcome could be greatly improved by the introduction of new orally administered agents, which may promote better adherence by avoiding injection- related problems (ref. 2) however few studies investigate adherence...

  9. Multicenter, open-label, non-comparative study of a combination of polytar and zinc pyrithione shampoo in the management of dandruff

    Directory of Open Access Journals (Sweden)

    Sawleshwarkar Shailendra

    2004-01-01

    Full Text Available Background: Dandruff is a common condition in clinical practice. We undertook a study to evaluate the efficacy and safety of a combination of zinc pyrithione and polytar in a shampoo base for the treatment of dandruff. Methods: A combination of polytar (1% and zinc pyrithione (1% was used for 4 weeks to treat 954 patients suffering from mild to severe dandruff. Scoring of dandruff was done on a 0-10 scale for each of the 6 regions of scalp at weeks 0, 2, 4 and 6. Follow up was for 2 weeks. Results: There was consistent improvement in dandruff scores over the treatment and the follow up period. There was significant improvement in signs and symptoms such as erythema and itching, with a negligible adverse event profile. The global assessment by investigators showed good-excellent results in the majority of patients and there was high acceptability for the treatment among the patients. Conclusion: A combination shampoo of polytar (1% and zinc pyrithione (1% offers a safe and effective option in the treatment of dandruff and its associated symptoms.

  10. Two-year outcomes in thoracic transplant recipients after conversion to everolimus with reduced calcineurin inhibitor within a multicenter, open-label, randomized trial

    DEFF Research Database (Denmark)

    Gullestad, Lars; Mortensen, Svend-Aage; Eiskjær, Hans

    2010-01-01

    Use of the mammalian target of rapamycin inhibitor everolimus with an accompanying reduction in calcineurin inhibitor (CNI) exposure has shown promise in preserving renal function in maintenance thoracic transplant patients, but robust, long-term data are required....

  11. Tacrolimus versus intravenous pulse cyclophosphamide therapy in Chinese adults with steroid-resistant idiopathic minimal change nephropathy: a multicenter, open-label, nonrandomized cohort trial.

    Science.gov (United States)

    Li, Heng; Shi, Xiangdong; Shen, Hong; Li, Xiayu; Wang, Huiping; Li, Hongmei; Xu, Guangbiao; Chen, Jianghua

    2012-05-01

    The treatment of steroid-resistant minimal change nephropathy (SR-MCN) in adults remains a challenge to nephrologists. Although immunosuppressants such as cyclophosphamide (CTX), chlorambucil, and cyclosporin A have been used in these patients, their use has been limited by low remission rates and severe adverse effects. Alternative immunosuppressive treatments for SR-MCN are therefore needed. The aim of this study was to compare the efficacy of tacrolimus (TAC) with that of intravenous (IV) pulse CTX therapy in the management of SR-MCN and to assess the tolerability of those treatments. This was a nonrandomized, case-matched trial in Chinese adults with SR-MCN. Patients were self-assigned to either: (1) combination therapy with prednisone and oral TAC; or (2) combination therapy with prednisone and IV CTX. TAC was initiated at 0.05 mg/kg/d and was adjusted to maintain a trough blood level of 5 to 10 ng/mL for 1 year. CTX was initiated at 1 g/1.73 m(2) for a total dosage of 10 g/1.73 m(2) over 1 year. In both groups, oral prednisone was initiated at 0.5 mg/kg/d for 3 months but was tapered off to complete cessation by 6 months. A total of 37 patients were enrolled (21 in the TAC group; 16 in the CTX group), of whom 33 (19 in the TAC group; 14 in the CTX group) completed the study. There were no significant difference in baseline demographic characteristics between the two treatment groups (The TAC group-mean age at onset, 28.8 [11.3]; mean age at trial, 29.6 [11.0]; male, 63.16%; The CTX group-mean age at onset, 34.4 [12.7]; mean age at trial, 35.9 [12.7]; male, 57.14%). The remission rates were 57.9%, 73.7%, and 78.9% in the TAC group and 14.3%, 42.9%, and 50.0% in the CTX group after 2, 4, and 6 months, respectively. The remission rate at 2 months was significantly higher in the TAC group than in the CTX group (P therapy and the 1-year follow-up were higher in the TAC group than in the CTX group (Kaplan-Meier curve, log-rank test, P therapy and 1-year follow-up periods, 6 of the 15 TAC-treated patients and 1 of the 7 CTX-treated patients relapsed (P = 0.35). These findings suggest that TAC therapy was effective compared with IV pulse CTX therapy in treating this select group of Chinese adults with SR-MCN. Both agents were well tolerated although TAC seemed to induce remission more rapidly than IV pulse CTX therapy. Australian New Zealand Clinical Trials Registry: study number ACTR 00362050. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

  12. A prospective, open-label, multicenter, observational, postmarket study of the use of a 15 mg/mL hyaluronic acid dermal filler in the lips.

    Science.gov (United States)

    Philipp-Dormston, Wolfgang G; Hilton, Said; Nathan, Myooran

    2014-06-01

    Hyaluronic acid (HA)-based injectable fillers three-dimensionally restore the natural contours of the lips and perioral area, thereby reducing some signs of aging lips. To evaluate the short-term aesthetic impact of treatment with the HA dermal filler Juvéderm(®) VOLBELLA(®) with Lidocaine, formulated utilizing VYCROSS(™) technology, for enhancement or correction of asymmetry of the lips, evaluated using a patient-centric approach. Sixty-two subjects were enrolled in this study, conducted at two sites in Germany. Primary endpoints were satisfaction with improvement, look and feel of the lips, assessed by subject and physician at first visit and 4 weeks post-treatment. Immediately after injection at first visit, 83.6% of subjects were Extremely Satisfied, Very Satisfied or Satisfied with improvement in the lips, which increased to 94.1% and 93.0% of subjects with/without top-up treatment at follow-up, respectively. After injection at first visit, 61.7% of subjects rated the look and feel of their lips as Extremely Natural or Very Natural, which increased to 75.0% and 93.0% of subjects with/without top-up treatment, respectively. The HA dermal filler was associated with minimal discomfort, bruising or swelling of the lips; almost two-thirds of subjects (62%) returned to social engagements on the same day. The high degree of subject satisfaction with aesthetic improvement in the lips, as well as the natural look and feel, indicates that this HA dermal filler represents an effective treatment option for patients requiring lip enhancement.

  13. Safety and performance of cohesive polydensified matrix hyaluronic acid fillers with lidocaine in the clinical setting – an open-label, multicenter study

    OpenAIRE

    Kühne U; Esmann J; von Heimburg D; Imhof M; Weissenberger P; Sattler G

    2016-01-01

    Ulrich Kühne,1 Jørgen Esmann,2 Dennis von Heimburg,3 Matthias Imhof,1 Petra Weissenberger,4 Gerhard Sattler,5 On behalf of the BALIA Study Group 1Aesthetische Dermatologie im Medico Palais, Bad Soden, Germany; 2Jørgen Esmann Aps, Hellerup, Denmark; 3Praxisklinik Kaiserplatz, Frankfurt am Main, Germany; 4Corporate Clinical Research, Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany; 5Rosenparkklinik GmbH, Darmstadt, Germany Abstract: Cohesive polydensified ma...

  14. Amisulpride plus valproate vs haloperidol plus valproate in the treatment of acute mania of bipolar I patients: a multicenter, open-label, randomized, comparative trial

    Directory of Open Access Journals (Sweden)

    Pierre Thomas

    2008-06-01

    Full Text Available Pierre Thomas1, Eduard Vieta2 for the SOLMANIA study group1Department of Psychiatry, Fontan Hospital CHRU Lille, University of Lille 2, France; 2Bipolar Disorders Program, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, SpainAbstract: The primary objective of this study was to compare the effectiveness of combination treatment of valproate and amisulpride with that of valproate and haloperidol in bipolar I disorder. Adult inpatients with a current manic episode fulfilling DSM-IV-TR diagnostic criteria for bipolar type I disorder were included. Patients were randomized to amisulpride (400–800 mg/day or haloperidol (5–15 mg/day for 3 months and all received valproate. The primary effectiveness criterion was the percentage of responders (defined by a decrease of ≥50% of the Y-MRS in patients completing the study. Safety was evaluated by adverse event reporting, determination of extrapyramidal function and clinical examination. Sixty-two patients were randomized to receive valproate-amisulpride, and 61 to receive valproate-haloperidol. At study end, responder rates were 72.6% in the amisulpride group and 65.5% in the haloperidol group. Remission rates were 83.9% and 89.7%, respectively. At study end, neither response rates nor remission rates differed significantly between groups. Treatment-emergent adverse events occurred significantly (p = 0.009 more frequently in the haloperidol group (86.4% than in the amisulpride group (66.1%. In conclusion, the valproate–amisulpride combination was as effective as the valproate – haloperidol combination in bipolar I patients, with a better safety profile.Keywords: amisulpride, valproate, haloperidol, clinical trial, mania, bipolar disorder

  15. Lanreotide Autogel in the Treatment of Idiopathic Refractory Diarrhea: Results of an Exploratory, Controlled, Before and After, Open-label, Multicenter, Prospective Clinical Trial.

    Science.gov (United States)

    Bisschops, Raf; De Ruyter, Vincent; Demolin, Gauthier; Baert, Didier; Moreels, Tom; Pattyn, Piet; Verhelst, Hans; Lepoutre, Luc; Arts, Joris; Caenepeel, Philip; Ooghe, Patrick; Codden, Thierry; Maisonobe, Pascal; Petrens, Elke; Tack, Jan

    2016-08-01

    Chronic idiopathic diarrhea is the passage of loose stools >3 times daily, or a stool weight >200 g/d, persisting for >4 weeks without clear clinical cause. Patients refractory to standard anti-diarrhetics have limited treatment options. Somatostatin analogues have the ability to reduce gastrointestinal secretions and motility. This study evaluated the efficacy and safety of lanreotide Autogel(*) 120 mg in chronic idiopathic diarrhea. Other anti-diarrhetics were not allowed during the study and were stopped at screening. Patients received lanreotide Autogel 120 mg at baseline and day 28. Stool frequency and consistency (Bristol Stool Scale) were recorded; quality of life (QoL) was assessed using the 36-item Short Form Health Survey and irritable bowel syndrome QoL questionnaires; adverse events were monitored. The primary outcome was the proportion of patients with a reduction of ≥50% or normalization to a mean of ≤3 stools/d at day 28. Thirty-three patients with >3 stools/d at baseline were included; mean (SD) age was 55.2 (16.4) years. Fourteen patients (42.4%) had a response to lanreotide Autogel at day 28 and 17 (51.5%) at day 56. Mean (SD) number of stools decreased significantly from 5.7 (2.2) at baseline to 3.7 (2.2) at day 56 overall (n = 32; P < 0.001). Significant and clinically meaningful improvements in disease-specific QoL were found in the overall populations. No new safety signals emerged. Lanreotide Autogel 120 mg decreased symptoms in these patients with chronic idiopathic refractory diarrhea, and meaningfully improved QoL. These finding have to be confirmed in further clinical trials. ClinicalTrials.gov NCT00891371; Eudract CT 2009-009356-20. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  16. A Multicenter, Randomized, Open-Labeled, Parallel Group Trial of Sildenafil in Alcohol-Associated Erectile Dysfunction: The Impact on Psychosocial Outcomes

    Directory of Open Access Journals (Sweden)

    Alexander Grinshpoon

    2009-09-01

    Full Text Available To examine the effect of sildenafil on erectile dysfunction (ED and psychosocial outcomes in alcohol-dependent (AD men, 108 men with these diagnoses were randomly assigned to either take sildenafil (50 mg as add-on to standard treatment for AD, or the same treatment without sildenafil, for 12 weeks. Only 50 patients in sildenafil group and 51 in control group twice completed the International Index of Erectile Function (IIEF and a battery of self-report questionnaires. IIEF scores and psychosocial functioning, self-esteem and support from friends improved only for sildenafil-treated patients (P < 0.001. The high effect sizes suggest that the observed benefits are unlikely to be a placebo effect, although their unspecific nature could not be ruled out. In men with ED associated with AD, sildenafil improves both ED and psychosocial outcomes. Further placebo-controlled clinical trial is warranted.

  17. Efficacy and safety of alternating norfloxacin and rifaximin as primary prophylaxis for spontaneous bacterial peritonitis in cirrhotic ascites: a prospective randomized open-label comparative multicenter study.

    Science.gov (United States)

    Assem, M; Elsabaawy, M; Abdelrashed, M; Elemam, S; Khodeer, S; Hamed, W; Abdelaziz, A; El-Azab, G

    2016-03-01

    Primary prevention of spontaneous bacterial peritonitis (SBP) is an important strategy to reduce morbidity and mortality in cirrhotic patients with ascites. Efficacy and safety of alternating rifaximin and norfloxacin as primary prophylaxis is questionable. Three hundred thirty-four cirrhotic patients with high SAAG (≥1.1) ascites, protein level in ascitic fluid less than 1.5 g/dL with advanced liver disease (Child-Pugh score >9 points with serum bilirubin level >3 mg/dL) or renal impairment (serum creatinine level >1.2 mg/dL, blood urea nitrogen level >25 mg/dL, or serum sodium level norfloxacin and rifaximin vs. norfloxacin or rifaximin alone as primary prophylaxis for SBP. Both intention-to-treat and per-protocol efficacy analyses were done after 6 months of treatment by assessment of ascitic fluid neutrophil count. Safety analysis was done for all intention-to-treat populations. Alternating norfloxacin and rifaximin showed superior prophylaxis by intention-to-treat (74.7 vs. 56.4% vs. 68.3%, p norfloxacin-based regimen in intention-to-treat (p = 0.016) and per protocol analysis (p = 0.039). There was no difference among the studied groups regarding the incidence and severity of adverse events reported. Alternating norfloxacin- and rifaximin-based primary prophylaxis for SBP showed higher efficacy with the same safety profile when compared with monotherapy of norfloxacin.

  18. A multicenter, open-label study of repeat courses of intramuscular alefacept in combination with other psoriasis therapies in patients with chronic plaque psoriasis.

    NARCIS (Netherlands)

    Krueger, G.G.; Gottlieb, A.B.; Sterry, W.; Korman, N.; Kerkhof, P Van De

    2008-01-01

    OBJECTIVE: To evaluate the safety and efficacy of multiple courses of alefacept in combination with traditional psoriasis therapy for the treatment of chronic plaque psoriasis (CPP). METHODS: Patients with CPP requiring systemic therapy were eligible for this study. Patients received up to three cou

  19. Phase IV open-label study of the efficacy and safety of deferasirox after allogeneic stem cell transplantation.

    Science.gov (United States)

    Vallejo, Carlos; Batlle, Montserrat; Vázquez, Lourdes; Solano, Carlos; Sampol, Antonia; Duarte, Rafael; Hernández, Dolores; López, Javier; Rovira, Montserrat; Jiménez, Santiago; Valcárcel, David; Belloch, Vicente; Jiménez, Mónica; Jarque, Isidro

    2014-10-01

    This is the first prospective study of deferasirox in adult allogeneic hematopoietic stem cell transplant recipients with transfusional iron overload in hematologic malignancies. Patients at least six months post transplant were treated with deferasirox at a starting dose of 10 mg/kg/day for 52 weeks or until serum ferritin was less than 400 ng/mL on two consecutive occasions. Thirty patients were enrolled and 22 completed the study. A significant reduction from baseline in median serum ferritin and in liver iron concentration at 52 weeks was observed in the overall population: from 1440 to 755.5 ng/mL (P=0.002) and from 14.5 to 4.6 mg Fe/g dw (P=0.0007), respectively. Reduction in serum ferritin in patients who did not discontinue deferasirox therapy was significantly greater than that found in those who prematurely discontinued the treatment (from 1541 to 581 ng/mL vs. from 1416 to 1486 ng/mL; P=0.008). Drug-related adverse events, reported in 17 patients (56.7%), were mostly mild to moderate in severity. There were no drug-related serious adverse events. Twelve patients (40.0%) showed an increase of over 33% in serum creatinine compared to baseline and greater than the upper limit of normal on two consecutive visits. Two patients (6.7%) with active graft-versus-host disease showed an increase in alanine aminotransferase exceeding 10 times upper limit of normal; both resolved. In this prospective study, deferasirox provided a significant reduction in serum ferritin and liver iron concentration over one year of treatment in allogeneic hematopoietic stem cell transplant recipients with iron overload. In addition, the majority of adverse events related to deferasirox were mild or moderate in severity. (clinicaltrials.gov identifier:01335035).

  20. Treatment with pentosan polysulphate in patients with MPS I: results from an open label, randomized, monocentric phase II study.

    Science.gov (United States)

    Hennermann, Julia B; Gökce, Seyfullah; Solyom, Alexander; Mengel, Eugen; Schuchman, Edward H; Simonaro, Calogera M

    2016-11-01

    Current treatment options for MPS I have limited effects on some organs, including the skeletal system. In MPS animal models pentosan polysulphate (PPS) reduces the concentrations of glycosaminoglycans (GAGs) in tissues and body fluids and improves cartilaginous and osseous pathologies. The goals of this study were to investigate primarily the safety and secondary the clinical effects, concerning mobility and pain, of PPS treatment in MPS I patients. Four MPS I-Hurler-Scheie/-Scheie patients aged 35.6 ± 6.4 years with one male were included in the study. All patients were on enzyme replacement therapy since 9.45 ± 3.75 years. PPS was applied subcutaneously in two patients with 1 mg/kg and in two patients with 2 mg/kg, weekly for 12 weeks and then biweekly for 12 weeks. The 24-week treatment with PPS was well tolerated by all patients. Urinary GAG concentrations were reduced from 4.13 ± 1.17 at baseline to 2.69 ± 0.36 mg/mmol creatinine after 24-week treatment with 1 mg/kg PPS, and from 6.71 ± 0.62 to 2.65 ± 0.09 mg/mmol creatinine with 2 mg/kg PPS. An improvement in range of motion was noted in three out of four patients. The pain intensity score was reduced from 4.5 ± 1.77 at baseline to 1.8 ± 0.47 after 24-week treatment with 1 mg/kg PPS; patients with 2 mg/kg PPS already had minimal pain at the start of the study. In conclusion, PPS treatment in a small number of adult MPS I patients was well tolerated and resulted in a significant reduction of urinary GAG excretion and in an improvement of joint mobility and pain.

  1. Intensified regimen containing rifampicin and moxifloxacin for tuberculous meningitis: an open-label, randomised controlled phase 2 trial.

    NARCIS (Netherlands)

    Ruslami, R.; Ganiem, A.R.; Dian, S.; Apriani, L.; Achmad, T.H.; Ven, A.J.A.M. van der; Borm, G.F.; Aarnoutse, R.E.; Crevel, R. van

    2013-01-01

    BACKGROUND: Intensified antibiotic treatment might improve the outcome of tuberculous meningitis. We assessed pharmacokinetics, safety, and survival benefit of several treatment regimens containing high-dose rifampicin and moxifloxacin in patients with tuberculous meningitis in a hospital setting. M

  2. Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia: 2-year interim results of an open-label extension.

    Science.gov (United States)

    Santos, Raul D; Duell, P Barton; East, Cara; Guyton, John R; Moriarty, Patrick M; Chin, Wai; Mittleman, Robert S

    2015-03-01

    To evaluate the efficacy and safety of extended dosing with mipomersen in patients with familial hypercholesterolaemia (HC) taking maximally tolerated lipid-lowering therapy. A planned interim analysis of an ongoing, open-label extension trial in patients (n = 141) with familial HC receiving a subcutaneous injection of 200 mg mipomersen weekly plus maximally tolerated lipid-lowering therapy for up to 104 weeks. The mean changes in low-density lipoprotein cholesterol (LDL-C) from baseline to weeks 26 (n = 130), 52 (n = 111), 76 (n = 66), and 104 (n = 53) were -28, -27, -27, and -28%; and in apolipoprotein B -29, -28, -30, and -31%, respectively. Reductions in total cholesterol, non-high-density lipoprotein-cholesterol, and lipoprotein(a) were comparable with decreases in LDL-C and apolipoprotein B levels. Mean high-density lipoprotein cholesterol increased from baseline by 7 and 6% at weeks 26 and 52, respectively. The long-term safety profile of mipomersen was similar to that reported in the associated randomized placebo-controlled Phase 3 trials. Adverse events included injection site reactions and flu-like symptoms. There was an incremental increase in the median liver fat during the initial 6-12 months that appeared to diminish with continued mipomersen exposure beyond 1 year and returned towards baseline 24 weeks after last drug dose suggestive of adaptation. The median alanine aminotransferase level showed a similar trend over time. Long-term treatment with mipomersen for up to 104 weeks provided sustained reductions in all atherosclerotic lipoproteins measured and a safety profile consistent with prior controlled trials in these high-risk patient populations. CLINICALTRIALS.GOV: NCT00694109. © The Author 2013. Published by Oxford University Press on behalf of the European Society of Cardiology.

  3. Open-label study of the short-term effects of memantine on FDG-PET in frontotemporal dementia

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    Chow TW

    2011-07-01

    Full Text Available Tiffany W Chow1–6, Ariel Graff-Guerrero4,6, Nicolaas PLG Verhoeff2–4,7, Malcolm A Binns3,8, David F Tang-Wai5,9, Morris Freedman1,3,5, Mario Masellis5,10, Sandra E Black3,5,10, Alan A Wilson4,6, Sylvain Houle4,6, Bruce G Pollock4,61Division of Neurology, 2Department of Psychiatry, 3Rotman Research Institute, Baycrest; 4Departments of Psychiatry, 5Medicine, Division of Neurology, University of Toronto; 6Centre for Addiction and Mental Health PET Centre; 7Kunin-Lunenfeld Applied Research Unit, Baycrest; 8Dalla Lana School of Public Health, University of Toronto; 9University Health Network Memory Clinic; 10LC Campbell Cognitive Neurology Research Unit, Department of Medicine (Neurology, Sunnybrook Health Sciences Centre, Toronto, ON, CanadaBackground: Memantine has shown effects on cortical metabolism in Alzheimer's disease (AD, and the mechanism of action may not be specific to AD alone. We hypothesized that participants with frontotemporal dementia taking memantine would show an increased cortical metabolic activity in frontal regions, temporal regions, or in salience network hubs.Methods: Sixteen participants with behavioral or language variant frontotemporal dementia syndromes (FTD were recruited from tertiary FTD clinics and treated with memantine hydrochloride 10 mg twice daily in this fixed-dose, open-label pilot study. The primary endpoint was enhancement of cortical metabolic activity after 7–8 weeks of treatment. Secondary endpoints were measures of mood and behavior disturbance, frontal executive function, and motor disturbance.Results: Voxel-wise parametric image analysis of positron emission tomography (PET data from seven behavioral variant FTD patients, eight semantic dementia patients, and one progressive nonfluent aphasia patient, of mean age 64.3 years, mean duration of illness 4.25 years, and baseline mean sum of boxes Clinical Dementia Rating score 6.59, revealed an increase in [18F]-fluorodeoxyglucose (FDG normalized

  4. Acceptability of an open-label wait-listed trial design: Experiences from the PROUD PrEP study

    Science.gov (United States)

    Brodnicki, Elizabeth; Desai, Monica; McCormack, Sheena; Nutland, Will; Wayal, Sonali; White, Ellen; Wood, Gemma; Barber, Tristan; Bell, Gill; Clarke, Amanda; Dolling, David; Dunn, David; Fox, Julie; Haddow, Lewis; Lacey, Charles; Nardone, Anthony; Quinn, Killian; Rae, Caroline; Reeves, Iain; Rayment, Michael; White, David; Apea, Vanessa; Ayap, Wilbert; Dewsnap, Claire; Collaco-Moraes, Yolanda; Schembri, Gabriel; Sowunmi, Yinka; Horne, Rob

    2017-01-01

    Background PROUD participants were randomly assigned to receive pre-exposure prophylaxis (PrEP) immediately or after a deferred period of one-year. We report on the acceptability of this open-label wait-listed trial design. Methods Participants completed an acceptability questionnaire, which included categorical study acceptability data and free-text data on most and least liked aspects of the study. We also conducted in-depth interviews (IDI) with a purposely selected sub-sample of participants. Results Acceptability questionnaires were completed by 76% (415/544) of participants. After controlling for age, immediate-group participants were almost twice as likely as deferred-group participants to complete the questionnaire (AOR:1.86;95%CI:1.24,2.81). In quantitative data, the majority of participants in both groups found the wait-listed design acceptable when measured by satisfaction of joining the study, intention to remain in the study, and interest in joining a subsequent study. However, three-quarters thought that the chance of being in the deferred-group might put other volunteers off joining the study. In free-text responses, data collection tools were the most frequently reported least liked aspect of the study. A fifth of deferred participants reported ‘being deferred’ as the thing they least liked about the study. However, more deferred participants disliked the data collection tools than the fact that they had to wait a year to access PrEP. Participants in the IDIs had a good understanding of the rationale for the open-label wait-listed study design. Most accepted the design but acknowledged they were, or would have been, disappointed to be randomised to the deferred group. Five of the 25 participants interviewed reported some objection to the wait-listed design. Conclusion The quantitative and qualitative findings suggest that in an environment where PrEP was not available, the rationale for the wait-listed trial design was well understood and

  5. An open-label pilot study of quetiapine plus mirtazapine for heavy drinkers with alcohol use disorder.

    Science.gov (United States)

    Brunette, Mary F; Akerman, Sarah C; Dawson, Ree; O'Keefe, Christopher D; Green, Alan I

    2016-06-01

    Animal research suggests that medications that produce a weak dopamine D2 receptor blockade and potentiate noradrenergic activity may decrease alcohol drinking. In an open-label pilot study of subjects with alcohol dependence, we tested whether the combination of quetiapine, a weak dopamine D2 receptor antagonist, whose primary metabolite, desalkylquetiapine, is a norepinephrine reuptake inhibitor, and mirtazapine, a potent α2 norepinephrine receptor antagonist, would decrease alcohol drinking and craving. Twenty very heavy drinkers with alcohol dependence entered a trial of 8 weeks of treatment with quetiapine followed by 8 weeks of treatment with a combination of quetiapine plus mirtazapine. Alcohol use was assessed weekly with a Timeline Follow-Back interview and craving with the Penn Alcohol Craving Scale. Among the 11 completers, subjects reported improved outcomes in the quetiapine plus mirtazapine period compared to the quetiapine alone period: fewer very heavy drinking days per week (1.3 [SD = 2.4] vs. 2.1 [SD = 2.8]; t = 2.3, df = 10, p = 0.04); fewer total number of drinks per week (39.7 [SD = 61.6] vs. 53.4 [SD = 65.0]; t = 2.8, df = 10, p = 0.02); and lower craving scores (2.5 [SD = 1.4] vs. 3.2 [SD = 1.2]; t = 2.4, df = 10, p = 0.04). All subjects reported at least one adverse event; 72.7% reported somnolence. In this open-label pilot study, treatment with quetiapine plus mirtazapine was associated with a decrease in alcohol drinking and craving. These findings are consistent with our previous work in animal models of alcohol use disorders and suggest that further study of medications or combinations of medications with this pharmacologic profile is warranted.

  6. Tipepidine in children with attention deficit/hyperactivity disorder: a 4-week, open-label, preliminary study

    Directory of Open Access Journals (Sweden)

    Sasaki T

    2014-01-01

    Full Text Available Tsuyoshi Sasaki,1,2 Kenji Hashimoto,3 Masumi Tachibana,1 Tsutomu Kurata,1 Keiko Okawada,1 Maki Ishikawa,1 Hiroshi Kimura,2 Hideki Komatsu,2 Masatomo Ishikawa,2 Tadashi Hasegawa,2 Akihiro Shiina,1 Tasuku Hashimoto,2 Nobuhisa Kanahara,3 Tetsuya Shiraishi,2 Masaomi Iyo1–31Department of Child Psychiatry, Chiba University Hospital, 2Department of Psychiatry, Chiba University Graduate School of Medicine, 3Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, JapanBackground: Tipepidine (3-[di-2-thienylmethylene]-1-methylpiperidine has been used solely as a nonnarcotic antitussive in Japan since 1959. The safety of tipepidine in children and adults has already been established. It is reported that tipepidine inhibits G-protein-coupled inwardly rectifying potassium (GIRK-channel currents. The inhibition of GIRK channels by tipepidine is expected to modulate the level of monoamines in the brain. We put forward the hypothesis that tipepidine can improve attention deficit/hyperactivity disorder (ADHD symptoms by modulating monoaminergic neurotransmission through the inhibition of GIRK channels. The purpose of this open-label trial was to confirm whether treatment with tipepidine can improve symptoms in pediatric patients with ADHD.Subjects and methods: This was a 4-week, open-label, proof-of-efficacy pilot study for pediatric subjects with ADHD. Ten pediatric ADHD subjects (70% male; mean age, 9.9 years; combined [inattentive and hyperactive/impulsive] subtype, n=7; inattentive subtype, n=3; hyperimpulsive subtype, n=0 received tipepidine hibenzate taken orally at 30 mg/day for 4 weeks. All subjects were assessed using the ADHD Rating Scale IV (ADHD-RS, Japanese version, and the Das–Naglieri Cognitive Assessment System (DN-CAS, Japanese version.Results: A comparison of baseline scores and 4-week end-point scores showed that all the ADHD-RS scores (total scores, hyperimpulsive subscores, and inattentive subscores

  7. Effect of open-label infusion of an apoA-I-containing particle (CER-001) on RCT and artery wall thickness in patients with FHA

    NARCIS (Netherlands)

    Kootte, Ruud S.; Smits, Loek P.; van der Valk, Fleur M.; Dasseux, Jean-Louis; Keyserling, Constance H.; Barbaras, Ronald; Paolini, John F.; Santos, Raul D.; van Dijk, Theo H.; Dallinga-van Thie, Geesje M.; Nederveen, Aart J.; Mulder, Willem J. M.; Hovingh, G. Kees; Kastelein, John J. P.; Groen, Albert K.; Stroes, Erik S.

    2015-01-01

    Reverse cholesterol transport (RCT) contributes to the anti-atherogenic effects of HDL. Patients with the orphan disease, familial hypoalphalipoproteinemia (FHA), are characterized by decreased tissue cholesterol removal and an increased atherogenic burden. We performed an open-label uncontrolled pr

  8. Effect of Micronutrients on Behavior and Mood in Adults with ADHD: Evidence from an 8-Week Open Label Trial with Natural Extension

    Science.gov (United States)

    Rucklidge, Julia; Taylor, Mairin; Whitehead, Kathryn

    2011-01-01

    Objective: To investigate the effect of a 36-ingredient micronutrient formula consisting mainly of minerals and vitamins in the treatment of adults with both ADHD and severe mood dysregulation (SMD). Method: 14 medication-free adults (9 men, 5 women; 18-55 years) with ADHD and SMD completed an 8-week open-label trial. Results: A minority reported…

  9. Sustained improvement in patient-reported outcomes during long-term fesoterodine treatment for overactive bladder symptoms: pooled analysis of two open-label extension studies.

    Science.gov (United States)

    Kelleher, Con J; Dmochowski, Roger R; Berriman, Sandra; Kopp, Zoe S; Carlsson, Martin

    2012-08-01

    • To evaluate the effects of long-term fesoterodine treatment on health-related quality of life (HRQL) and treatment satisfaction in subjects with overactive bladder (OAB) symptoms. • To determine the impact of gender and age on these effects. • This is a post hoc analysis of data pooled from identically designed open-label extensions of two randomized, double-blind, 12-week fesoterodine studies. • Initial treatment was once-daily fesoterodine 8 mg; subjects had the opportunity to receive open-label fesoterodine for ≥24 months. • After 1 month, subjects could elect dose reduction to 4 mg and subsequent re-escalation to 8 mg; dose reduction and re-escalation were each allowed once annually. • Changes in scores on the King's Health Questionnaire (KHQ), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and a Likert scale evaluating severity of bladder-related problems were assessed at open-label baseline and months 12 and 24; treatment satisfaction was assessed at open-label baseline and at months 4, 12 and 24. • A total of 864 enrolled subjects were included (men, n= 182; women, n= 682; aged fesoterodine treatment was associated with sustained improvement in measures of health-related quality of life and bladder-related problems and with high treatment satisfaction in subjects with overactive bladder symptoms. • Effects of gender and age were minimal. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

  10. Efficacy of Atomoxetine for the Treatment of ADHD Symptoms in Patients with Pervasive Developmental Disorders: A Prospective, Open-Label Study

    Science.gov (United States)

    Fernandez-Jaen, Alberto; Fernandez-Mayoralas, Daniel Martin; Calleja-Perez, Beatriz; Munoz-Jareno, Nuria; Campos Diaz, Maria del Rosario; Lopez-Arribas, Sonia

    2013-01-01

    Objective: Atomoxetine's tolerance and efficacy were studied in 24 patients with pervasive developmental disorder and symptoms of ADHD. Method: Prospective, open-label, 16-week study was performed, using the variables of the Clinical Global Impression Scale and the Conners' Scale, among others. Results: A significant difference was found between…

  11. Efficacy of Atomoxetine for the Treatment of ADHD Symptoms in Patients with Pervasive Developmental Disorders: A Prospective, Open-Label Study

    Science.gov (United States)

    Fernandez-Jaen, Alberto; Fernandez-Mayoralas, Daniel Martin; Calleja-Perez, Beatriz; Munoz-Jareno, Nuria; Campos Diaz, Maria del Rosario; Lopez-Arribas, Sonia

    2013-01-01

    Objective: Atomoxetine's tolerance and efficacy were studied in 24 patients with pervasive developmental disorder and symptoms of ADHD. Method: Prospective, open-label, 16-week study was performed, using the variables of the Clinical Global Impression Scale and the Conners' Scale, among others. Results: A significant difference was found between…

  12. Effect of enzyme therapy and prognostic factors in 69 adults with Pompe disease : an open-label single-center study

    NARCIS (Netherlands)

    de Vries, Juna M.; van der Beek, Nadine A. M. E.; Hop, Wim C. J.; Karstens, Francois P. J.; Wokke, John H.; de Visser, Marianne; van Engelen, Baziel G. M.; Kuks, Jan B. M.; van der Kooi, Anneke J.; Notermans, Nicolette C.; Faber, Catharina G.; Verschuuren, Jan J. G. M.; Kruijshaar, Michelle E.; Reuser, Arnold J. J.; van Doorn, Pieter A.; van der Ploeg, Ans T.

    2012-01-01

    Background: Enzyme replacement therapy (ERT) in adults with Pompe disease, a progressive neuromuscular disorder, is of promising but variable efficacy. We investigated whether it alters the course of disease, and also identified potential prognostic factors. Methods: Patients in this open-label

  13. Effect of Micronutrients on Behavior and Mood in Adults with ADHD: Evidence from an 8-Week Open Label Trial with Natural Extension

    Science.gov (United States)

    Rucklidge, Julia; Taylor, Mairin; Whitehead, Kathryn

    2011-01-01

    Objective: To investigate the effect of a 36-ingredient micronutrient formula consisting mainly of minerals and vitamins in the treatment of adults with both ADHD and severe mood dysregulation (SMD). Method: 14 medication-free adults (9 men, 5 women; 18-55 years) with ADHD and SMD completed an 8-week open-label trial. Results: A minority reported…

  14. Efficacy of Folic Acid Supplementation in Autistic Children Participating in Structured Teaching: An Open-Label Trial

    Directory of Open Access Journals (Sweden)

    Caihong Sun

    2016-06-01

    Full Text Available Autism spectrum disorders (ASD are recognized as a major public health issue. Here, we evaluated the effects of folic acid intervention on methylation cycles and oxidative stress in autistic children enrolled in structured teaching. Sixty-six autistic children enrolled in this open-label trial and participated in three months of structured teaching. Forty-four children were treated with 400 μg folic acid (two times/daily for a period of three months during their structured teaching (intervention group, while the remaining 22 children were not given any supplement for the duration of the study (control group. The Autism Treatment Evaluation Checklist (ATEC and Psychoeducational Profile-third edition (PEP-3 were measured at the beginning and end of the treatment period. Folic acid, homocysteine, and glutathione metabolism in plasma were measured before and after treatment in 29 autistic children randomly selected from the intervention group and were compared with 29 age-matched unaffected children (typical developmental group. The results illustrated folic acid intervention improved autism symptoms towards sociability, cognitive verbal/preverbal, receptive language, and affective expression and communication. Furthermore, this treatment also improved the concentrations of folic acid, homocysteine, and normalized glutathione redox metabolism. Folic acid supplementation may have a certain role in the treatment of children with autism.

  15. Effects of risperidone on core symptoms of autistic disorder based on childhood autism rating scale: An open label study

    Directory of Open Access Journals (Sweden)

    Padideh Ghaeli

    2014-01-01

    Full Text Available Background: The aim of the present study was to evaluate the effect of risperidone in patients afflicted by autistic disorder especially with regards to its three core symptoms, including "relating to others", "communication skills", and "stereotyped behaviors" based on Childhood Autism Rating Scale (CARS. Materials and Methods: An 8-week open-label study of risperidone for treatment of autistic disorder in children 4-17 years old was designed. Risperidone dose titration was as follow: 0.02 mg/kg/day at the first week, 0.04 mg/kg/day at the second week, and 0.06 mg/kg/day at the third week and thereafter. The outcome measures were scores obtained by CARS, Aberrant Behavior Checklist (ABC, and Clinical Global Impression-Improvement (CGI-I scale. Results: Fifteen patients completed this study. After 8 weeks, CARS total score decreased significantly, (P=0.001. At the end of the study, social interactions and verbal communication skills of the patients were significantly improved (P<0.001, P=0.03, respectively. However, stereotypic behaviors did not show any significant change in this study. Increase in appetite and somnolence were the most reported side effects. Conclusion: This study suggests that risperidone may be an effective treatment for the management of core symptoms of autistic disorder.

  16. Reduction of tinnitus severity by the centrally acting muscle relaxant cyclobenzaprine: an open-label pilot study.

    Science.gov (United States)

    Coelho, Claudia; Figueiredo, Ricardo; Frank, Elmar; Burger, Julia; Schecklmann, Martin; Landgrebe, Michael; Langguth, Berthold; Elgoyhen, Ana Belen

    2012-01-01

    Tinnitus, the phantom perception of sounds, is a highly prevalent disorder. Although a wide variety of drugs have been investigated off label for the treatment of tinnitus, there is no approved pharmacotherapy. We report an open-label exploratory pilot study to assess the effect of muscle relaxants acting on the central nervous system on tinnitus patients. Cyclobenzaprine at high (30 mg) and low doses (10 mg), orphenadrine (100 mg), tizanidine (24 mg) and eperisone (50 mg) were administered to a maximum of 20 patients per group over a 12-week period. High-dose cyclobenzaprine resulted in a significant reduction in the Tinnitus Handicap Inventory (THI) score between baseline and week 12 in the intention-to-treat sample. On the other hand, other treatments were not effective. These results were confirmed in an explorative analysis where baseline corrected THI and Clinical Global Impression scores at week 12 were compared between groups. The present open trial presents a new promising pharmacotherapy for tinnitus that should be validated in placebo-controlled double-blind trials.

  17. Efficacy of Folic Acid Supplementation in Autistic Children Participating in Structured Teaching: An Open-Label Trial.

    Science.gov (United States)

    Sun, Caihong; Zou, Mingyang; Zhao, Dong; Xia, Wei; Wu, Lijie

    2016-06-07

    Autism spectrum disorders (ASD) are recognized as a major public health issue. Here, we evaluated the effects of folic acid intervention on methylation cycles and oxidative stress in autistic children enrolled in structured teaching. Sixty-six autistic children enrolled in this open-label trial and participated in three months of structured teaching. Forty-four children were treated with 400 μg folic acid (two times/daily) for a period of three months during their structured teaching (intervention group), while the remaining 22 children were not given any supplement for the duration of the study (control group). The Autism Treatment Evaluation Checklist (ATEC) and Psychoeducational Profile-third edition (PEP-3) were measured at the beginning and end of the treatment period. Folic acid, homocysteine, and glutathione metabolism in plasma were measured before and after treatment in 29 autistic children randomly selected from the intervention group and were compared with 29 age-matched unaffected children (typical developmental group). The results illustrated folic acid intervention improved autism symptoms towards sociability, cognitive verbal/preverbal, receptive language, and affective expression and communication. Furthermore, this treatment also improved the concentrations of folic acid, homocysteine, and normalized glutathione redox metabolism. Folic acid supplementation may have a certain role in the treatment of children with autism.

  18. Onabotulinumtoxin A Treatment of Drooling in Children with Cerebral Palsy: A Prospective, Longitudinal Open-Label Study

    DEFF Research Database (Denmark)

    Møller, Eigild; Pedersen, Søren Anker; Vinicoff, Pablo Gustavo;

    2015-01-01

    The aim of this prospective open-label study was to treat disabling drooling in children with cerebral palsy (CP) with onabotulinumtoxin A (A/Ona, Botox®) into submandibular and parotid glands and find the lowest effective dosage and least invasive method. A/Ona was injected in 14 children, Mean...... age 9 years, SD 3 years, under ultrasonic guidance in six successive Series, with at least six months between injections. Doses and gland involvement increased from Series A to F (units (U) per submandibular/parotid gland: A, 10/0; B, 15/0; C, 20/0; D, 20/20; E, 30/20; and F, 30/30). The effect...... in E and F, but with swallowing problems ≤5 weeks in 3 of 28 treatments. F had largest VAS and UWS reduction (64% and 49%). We recommend: Start with dose D A/Ona (both submandibular and parotid glands and a total of 80 U) and increase to E and eventually F (total 120 U) without sufficient response....

  19. Effect of Repeated Anthelminthic Treatment on Malaria in School Children in Kenya: A Randomized, Open-Label, Equivalence Trial.

    Science.gov (United States)

    Kepha, Stella; Nuwaha, Fred; Nikolay, Birgit; Gichuki, Paul; Mwandawiro, Charles S; Mwinzi, Pauline N; Odiere, Maurice R; Edwards, Tansy; Allen, Elizabeth; Brooker, Simon J

    2016-01-15

    School children living in the tropics are often concurrently infected with plasmodium and helminth parasites. It has been hypothesized that immune responses evoked by helminths may modify malaria-specific immune responses and increase the risk of malaria. We performed a randomized, open-label, equivalence trial among 2436 school children in western Kenya. Eligible children were randomized to receive either 4 repeated doses or a single dose of albendazole and were followed up during 13 months to assess the incidence of clinical malaria. Secondary outcomes were Plasmodium prevalence and density, assessed by repeat cross-sectional surveys over 15 months. Analysis was conducted on an intention-to-treat basis with a prespecified equivalence range of 20%. During 13 months of follow-up, the incidence rate of malaria was 0.27 episodes/person-year in the repeated treatment group and 0.26 episodes/person-year in the annual treatment group (incidence difference, 0.01; 95% confidence interval, -.03 to .06). The prevalence and density of malaria parasitemia did not differ by treatment group at any of the cross-sectional surveys. Our findings suggest that repeated deworming does not alter risks of clinical malaria or malaria parasitemia among school children and that school-based deworming in Africa may have no adverse consequences for malaria. NCT01658774. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

  20. Adalimumab induction therapy for ulcerative colitis with intolerance or lost response to infliximab: An open-label study

    Institute of Scientific and Technical Information of China (English)

    Laurent Peyrin-Biroulet; Cécils Laclotte; Xavier Roblin; Marc-André Bigard

    2007-01-01

    AIM: To evaluate the efficacy of adalimumab induction therapy in patients with ulcerative colitis who previously responded to infliximab and then lost response or became intolerant.METHODS: Ten patients with ulcerative colitis were enrolled in a 4-wk open-label trial. The patients received a loading dose of 160 mg adalimumab at wk 0 followed by 80 mg at wk 2. The primary efficacy measure was clinical improvement at wk 4, as defined by a decrease in clinical activity index (CAI) of more than 4.RESULTS: Four of 10 patients (40%) benefited from subsequent adalimumab therapy; one patient achieved remission (CAI < 4) and 3 had clinical improvement at wk 4. 6 patients had no response (60%); 2 of 6 (33.3%) subsequently underwent colectomy. This was accompanied by a decrease in median CRP concentration from 16.8 mg/mL at baseline to 3.85 mg/mL at wk 4, excluding two patients who underwent colectomy after two infusions of adalimumab. Among the 6 patients with severe colitis (CAI > 12) at baseline, none achieved remission and only one patient had clinical improvement at wk 4.CONCLUSION: The small advantage of adalimumab in patients with mild to moderate ulcerative colitis and lost response or intolerance to infliximab needs to be confirmed in randomised, double-blind, placebocontrolled trials.

  1. An Open-Label Pilot Study to Assess the Efficacy and Safety of Virgin Coconut Oil in Reducing Visceral Adiposity

    Science.gov (United States)

    Liau, Kai Ming; Lee, Yeong Yeh; Chen, Chee Keong; Rasool, Aida Hanum G.

    2011-01-01

    Introduction. This is an open-label pilot study on four weeks of virgin coconut oil (VCO) to investigate its efficacy in weight reduction and its safety of use in 20 obese but healthy Malay volunteers. Methodology. Efficacy was assessed by measuring weight and associated anthropometric parameters and lipid profile one week before and one week after VCO intake. Safety was assessed by comparing organ function tests one week before and one week after intake of VCO. Paired t-test was used to analyse any differences in all the measurable variables. Results. Only waist circumference (WC) was significantly reduced with a mean reduction of 2.86 cm or 0.97% from initial measurement (P = .02). WC reduction was only seen in males (P < .05). There was no change in the lipid profile. There was a small reduction in creatinine and alanine transferase levels. Conclusion. VCO is efficacious for WC reduction especially in males and it is safe for use in humans. PMID:22164340

  2. Effects of flexible-dose fesoterodine on overactive bladder symptoms and treatment satisfaction: an open-label study

    Science.gov (United States)

    Wyndaele, J-J; Goldfischer, E R; Morrow, J D; Gong, J; Tseng, L-J; Guan, Z; Choo, M-S

    2009-01-01

    Aims: To evaluate the efficacy and tolerability of flexible-dose fesoterodine in subjects with overactive bladder (OAB) who were dissatisfied with previous tolterodine treatment. Methods: This was a 12-week, open-label, flexible-dose study of adults with OAB (≥ 8 micturitions and ≥ 3 urgency episodes per 24 h) who had been treated with tolterodine (immediate- or extended-release) for OAB within 2 years of screening and reported dissatisfaction with tolterodine treatment. Subjects received fesoterodine 4 mg once daily for 4 weeks; thereafter, daily dosage was maintained at 4 mg or increased to 8 mg based on the subject’s and physician’s subjective assessment of efficacy and tolerability. Subjects completed 5-day diaries, the Patient Perception of Bladder Condition (PPBC) and the Overactive Bladder Questionnaire (OAB-q) at baseline and week 12 and rated treatment satisfaction at week 12 using the Treatment Satisfaction Question (TSQ). Safety and tolerability were assessed. Results: Among 516 subjects treated, approximately 50% opted for dose escalation to 8 mg at week 4. Significant improvements from baseline to week 12 were observed in micturitions, urgency urinary incontinence episodes, micturition-related urgency episodes and severe micturition-related urgency episodes per 24 h (all pfesoterodine significantly improved OAB symptoms, HRQL, and rates of treatment satisfaction and was well tolerated in subjects with OAB who were dissatisfied with prior tolterodine therapy. PMID:19348029

  3. Effect of high-dose phenobarbital on oxidative stress in perinatal asphyxia: an open label randomized controlled trial.

    Science.gov (United States)

    Gathwala, Geeta; Marwah, Ashish; Gahlaut, Veena; Marwah, Poonam

    2011-08-01

    To evaluate the effect of high dose phenobarbital on lipid peroxidation and antioxidant enzymes in perinatal asphyxia. Open label, Randomized controlled trial. Neonatal intensive care unit of a tertiary care teaching hospital. 72 full term inborn neonates with severe birth asphyxia. Neonates were randomized to Study (phenobarbital) group and Control group. The infants in the study group received phenobarbital infusion (40 mg/kg) within first two hours of life while babies in the control group did not receive any phenobarbital. Rest of the management in both the groups was as per the unit protocol for the management of hypoxic ischemic encephalopathy. A cerebrospinal fluid examination was done at 12 ± 2 hours of life to determine the levels of superoxide dismutase, glutathione peroxidise and malonyldialdehyde. 60 neonates were followed up at 1 month of age when a detailed neurological examination was done. Four neonates in the study group and six neonates in the control group died during the study. Two neonates in the study group were lost to follow up. The cerebrospinal fluid lipid peroxides and antioxidant enzymes were significantly lower in the phenobarbital group as compared to the control group. The neurological outcome at one month follow up was found to be comparable between the two groups. Phenobarbital (40 mg/kg) given in the first two hours of life in term neonates with perinatal asphyxia led to a decrease in CSF levels of lipid peroxides and antioxidant enzymes at 12 ± 2 hours of life.

  4. Micronutrients supplementation and nutritional status in cognitively impaired elderly persons: a two-month open label pilot study.

    Science.gov (United States)

    von Arnim, Christine A F; Dismar, Stephanie; Ott-Renzer, Cornelia S; Noeth, Nathalie; Ludolph, Albert C; Biesalski, Hans K

    2013-11-15

    Malnutrition is a widespread problem in elderly people and is associated with cognitive decline. However, interventional studies have produced ambiguous results. For this reason, we wanted to determine the effect of micronutrient supplementation on blood and tissue levels and on general nutritional status in persons with mild or moderate cognitive impairment. We performed a 2-month, open-label trial, administering a daily micronutrient supplement to 42 memory clinic patients with mild cognitive deficits. Blood levels of antioxidants, zinc, and B vitamins were determined before and after supplementation. In addition, we assessed metabolic markers for B vitamins and intracellular (buccal mucosa cell [BMC]) antioxidant levels. Nutritional status was assessed by using the Mini Nutritional Assessment (MNA). Blood levels of B vitamins, folic acid, lutein, β-carotene, α-carotene, and α-tocopherol increased significantly. Decreases in homocysteine levels and the thiamine pyrophosphate effect and an increase in holotranscobalamin were observed. We found no increase in intracellular antioxidant levels of BMC. The MNA score in subjects at risk for malnutrition increased significantly, mainly owing to better perception of nutritional and overall health status. Micronutrient supplementation improved serum micronutrient status, with improved metabolic markers for B vitamins but not for intracellular antioxidant status, and was associated with improved self-perception of general health status. Our data underline the necessity of determining micronutrient status and support the use of additional assessments for general health and quality of life in nutritional supplementation trials.

  5. Effect of topical vitamin D on chronic kidney disease-associated pruritus: An open-label pilot study.

    Science.gov (United States)

    Jung, Kyung Eun; Woo, Yu Ri; Lee, Joong Sun; Shin, Jong Ho; Jeong, Jin Uk; Koo, Dae Won; Bang, Ki Tae

    2015-08-01

    Chronic kidney disease-associated pruritus (CKD-aP) is a troublesome symptom in patients with end-stage renal disease (ESRD). Recently, vitamin D deficiency has been known to be one of the possible etiologic factors in CKD-aP. However, limited data is available on whether topical vitamin D treatment is effective for relieving CKD-aP. Therefore, the purpose of this study is to evaluate the effectiveness of topically vitamin D for CKD-aP. Twenty-three patients with CKD-aP were enrolled in a single center, open-label study. Patients were instructed to apply a topical vitamin D (calcipotriol) agent (Daivonex solution; LEO Pharma) or vehicle solution twice daily for a month. We assessed the efficacy and safety of topical vitamin D on CKD-aP using clinical and dermoscopic photographs, and questionnaires including the validated modified pruritus assessment score (VMPAS) and visual analog scale (VAS) every 2 weeks. Dry dermoscopic findings showed significant improvement of scale (dryness) on the skin of topical vitamin D-treated patients compared with those of the vehicle group. Both VMPAS and VAS were significantly decreased after 2 and 4 weeks of the topical vitamin D treatment compared with the vehicle, respectively (P < 0.05). No significant side-effects were observed. Topical vitamin D may be one of the safe and effective therapeutic candidates for CKD-aP.

  6. Treprostinil sodium (Remodulin), a prostacyclin analog, in the treatment of critical limb ischemia: open-label study.

    Science.gov (United States)

    Berman, Scott; Quick, Rhonda; Yoder, Pam; Voigt, Sonia; Strootman, Deborah; Wade, Michael

    2006-01-01

    The purpose of this study was to assess the safety of continuous subcutaneous therapy with treprostinil sodium (Remodulin), a prostacyclin analog, and its effect on ischemic rest pain and ischemic wound healing in subjects with critical limb ischemia (CLI) and no planned revascularization procedure. This was a 12-week, open-label, single-center pilot study enrolling 10 subjects (mean age 82.4 years) with Fontaine stage III to IV (Rutherford class 4-6) peripheral arterial disease and ankle brachial indices less than 0.55. The primary end point was safety, and the secondary end points were the effects of treatment on ischemic rest pain, limb salvage, and wound healing. There was a 62% reduction in mean worst rest pain and a 57% reduction in mean average rest pain at week 12, with most subjects using less pain medication. Three subjects experienced complete healing of their wounds. No subject developed a new wound during the trial. Treprostinil was generally well tolerated. Subcutaneous infusion-site pain was the most frequently reported side effect, with one subject withdrawing from the study as a result. Jaw pain was reported by two subjects. One subject experienced two serious adverse events considered unrelated to treprostinil (cholecystitis and congestive heart failure). This study demonstrates that chronic, continuous subcutaneous treprostinil is safe and can be useful in the treatment of ischemic pain and wounds in subjects with CLI. Future controlled studies are needed to evaluate these effects and determine appropriate patient selection.

  7. Pharmacokinetics, safety, and tolerability of a depot formulation of naltrexone in alcoholics: an open-label trial

    Directory of Open Access Journals (Sweden)

    Koch Monika

    2005-04-01

    Full Text Available Abstract Background Naltrexone is an effective medication for treatment of alcohol dependence, but its efficacy is limited by lack of adherence to the oral dosage form. A long-acting depot formulation of naltrexone may increase adherence. Methods A single site, 6-week open label study was conducted with 16 alcohol dependent subjects each receiving 300 mg of Naltrexone Depot by intramuscular injection. The main outcomes were safety and tolerability of the Naltrexone Depot formulation, blood levels of naltrexone and its main metabolite 6-beta naltrexol, and self-reported alcohol use. All subjects received weekly individual counseling sessions. Results The medication was well tolerated with 88% of subjects completing the 6-week trial. The most common side effect experienced was injection site complications. There were no serious adverse events. Subjects had naltrexone and 6-beta-naltrexol concentrations throughout the trial with mean values ranging from 0.58 ng/mL to 2.04 ng/mL and 1.51 ng/mL to 5.52 ng/mL, respectively, at each sampling time following administration. Compared to baseline, subjects had significantly reduced number of drinks per day, heavy drinking days and proportion of drinking days. Conclusion Naltrexone Depot is safe and well tolerated in alcoholics and these findings support the further investigation of its utility in larger double-blind placebo controlled trials.

  8. 4-WEEK OPEN-LABEL CONTROLLED RANDOMIZED COMPARATIVE STUDY OF THE INJECTABLE AND TABLETTED FORMULATIONS OF METHOTREXATE IN RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    Yu. V. Muravyev

    2011-01-01

    Full Text Available Objective: to estimate the advantages and disadvantages of using the injectable formulation of methotrexate (MT (Methoject (MTJ in rheumatoid arthritis (RA in clinical practice. Subjects and methods. A 24-week open-label controlled randomized comparative study evaluated the therapeutic and side effects of MTJ and methotrexate tablets in RA and clarified whether MTJ treatment might be continued if its tabletted formulation was discontinued because of adverse reactions. Results and discussion. MTJ was found to be more effective than the tabletted formulation of MT and as a whole; and following 3-month therapy, more patients receiving MTJ achieved an ACR20 response. The advantage of MTJ was also retained 6 months after therapy. Higher transaminase levels were noted in 2 patients, one in each group. Switching from MT to MTJ noticeably reduced the number of adverse reactions in the majority of patients from an additional group. Conclusion. As compared to MT, MTJ used in RA patients is more effective when given in an equivalent dose, exerts a therapeutic effect more rapidly, and induces adverse gastrointestinal reactions less frequently. 

  9. A multi-center, comparative, phase 3 study to determine the efficacy of gadofosveset-enhanced magnetic resonance angiography for evaluation of renal artery disease

    Energy Technology Data Exchange (ETDEWEB)

    McGregor, Robert [St. Boniface General Hospital, Winnipeg, Manitoba (Canada); Vymazal, Josef [Hospital Na Homolce, Prague (Czech Republic); Martinez-Lopez, Manuel [Hospital Medica Sur, Mexico City (Mexico); Neuwirth, Jiri [Faculty Hospital Motol, Prague (Czech Republic); Salgado, Perla [American British Cowdray Medical Center, Mexico City (Mexico); Beregi, Jean-Paul [Hopital Cardiologique, Lille (France); Peduto, Anthony [Westmead Hospital, Westmead New South Wales (Australia); Pena-Almaguer, Erasmo de la [Christus-Muguerza Medical Center, Monterrey, Nuevo Leon (Mexico); Slater, Greg J. [Greenslopes Private Hospital, Greenslopes, Queensland (Australia); Shamsi, Kohkan [Berlex Laboratories, Montville, NJ (United States); Parsons, Edward C. [EPIX Pharmaceuticals, Inc., Lexington, MA (United States)], E-mail: eparsons@epixpharma.com

    2008-02-15

    Purpose: To determine prospectively the safety and efficacy of the blood-pool contrast agent gadofosveset trisodium in renal artery magnetic resonance angiography (MRA). Materials and methods: Gadofosveset (0.03 mmol/kg) was administered to adult patients with known or suspected renal arterial disease in a multi-center phase 3 single dose study. The drug binds reversibly to albumin, prolonging the blood residence time, and allowing collection of images in the first-pass and steady-state phases. The combination of these images was compared to non-contrast MRA, using catheter X-ray angiography (XRA) as the standard of reference (SOR). All MRA images were collected at 1.5 T in one imaging session for direct comparison, and XRA within 30 days. Sensitivity, specificity, and accuracy for diagnosing significant disease (stenosis {>=}50%) were calculated for MRA using three independent blinded readers. Patient safety was monitored for 72-96 h. Results: A total of 145 patients at 18 centers were enrolled and received gadofosveset; the 127 with complete efficacy data entered the primary efficacy analysis. Gadofosveset-enhanced MRA led to significant improvement (p < 0.01) in sensitivity (+25%, +26%, +42%), specificity (+23%, +25%, +29%), and accuracy (+23%, +28%, +29%) over non-enhanced MRA for the three readers. The rate of uninterpretable examinations decreased from 30% to less than 2%. There were no serious adverse events, and the most common adverse events were nausea, pruritis, and headache (8% each). No significant trends in clinical chemistry parameters, nor significant changes in serum creatinine, were found following administration of gadofosveset. Conclusion: In patients with known or suspected renal arterial disease, multi-phase gadofosveset-enhanced MRA significantly improves sensitivity, specificity, and accuracy versus non-enhanced MRA. Gadofosveset was safe and well tolerated in this patient population.

  10. An open-label study of algorithm-based treatment versus treatment-as-usual for patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Hirano J

    2013-10-01

    Full Text Available Jinichi Hirano,1,2 Koichiro Watanabe,3 Takefumi Suzuki,1,4 Hiroyuki Uchida,1 Ryosuke Den,5 Taishiro Kishimoto,1 Takashi Nagasawa,5 Yusuke Tomita,4 Koichiro Hara,6 Hiromi Ochi,7 Yoshimi Kobayashi,1 Mutsuko Ishii,1 Akane Fujita,1 Yoshihiko Kanai,1 Megumi Goto,1 Hiromi Hayashi,1 Kanako Inamura,1 Fumiko Ooshima,1 Mariko Sumida,1 Tomoko Ozawa,1 Kayoko Sekigawa,1 Maki Nagaoka,1 Kae Yoshimura,1 Mika Konishi,1 Ataru Inagaki,1 Takuya Saito,8 Nobutaka Motohashi,9 Masaru Mimura,1 Yoshiro Okubo,8 Motoichiro Kato,11Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; 2Ohizumi Hospital, Tokyo, Japan; 3Department of Psychiatry School of Medicine, Kyorin University, Tokyo, Japan; 4Inokashira Hospital, Tokyo, Japan; 5Komagino Hospital, Tokyo, Japan; 6Asai Hospital, Chiba, Japan; 7Kurumegaoka Hospital, Tokyo, Japan; 8Department of Psychiatry School of Medicine, Nippon Medical School, Tokyo, Japan; 9Department of Psychiatry, School of Medicine, University of Yamanashi, Yamanashi, JapanObjective: The use of an algorithm may facilitate measurement-based treatment and result in more rational therapy. We conducted a 1-year, open-label study to compare various outcomes of algorithm-based treatment (ALGO for schizophrenia versus treatment-as-usual (TAU, for which evidence has been very scarce.Methods: In ALGO, patients with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, fourth edition were treated with an algorithm consisting of a series of antipsychotic monotherapies that was guided by the total scores in the positive and negative syndrome scale (PANSS. When posttreatment PANSS total scores were above 70% of those at baseline in the first and second stages, or above 80% in the 3rd stage, patients proceeded to the next treatment stage with different antipsychotics. In contrast, TAU represented the best clinical judgment by treating psychiatrists.Results: Forty-two patients (21 females, 39.0 ± 10.9 years

  11. A Phase IIIb, randomized, double-blind, placebo-controlled, multicenter study evaluating the safety and efficacy of dexmedetomidine for sedation during awake fiberoptic intubation.

    Science.gov (United States)

    Bergese, Sergio D; Candiotti, Keith A; Bokesch, Paula M; Zura, Andrew; Wisemandle, Wayne; Bekker, Alex Y

    2010-01-01

    GABA-mediated sedatives have respiratory depressant properties that may be detrimental in patients with difficult airways. In this randomized, double-blind, multicenter, Phase IIIb Food and Drug Administration study, safety and efficacy of dexmedetomidine compared with placebo were evaluated as the primary sedative for awake fiberoptic intubation (AFOI). Patients were randomized to receive dexmedetomidine or saline. Patients were sedated with dexmedetomidine or rescue midazolam to achieve targeted sedation (Ramsay Sedation Scale ≥ 2) before topicalization and throughout AFOI. Primary efficacy endpoint was percentage of patients requiring rescue midazolam; secondary efficacy endpoints were total dose of rescue midazolam, percentage requiring additional rescue nonmidazolam medications, anesthesiologist's assessment of ease of subject care, and patient recall and satisfaction 24 hours postoperatively. Less rescue midazolam was required to maintain Ramsay Sedation Scale ≥2 (47.3% vs. 86.0%, P sedated with midazolam. Patients and anesthesiologists showed favorable satisfaction responses in both groups. Adverse events and patient recall were similar in both groups. Dexmedetomidine is effective as the primary sedative in patients undergoing AFOI. Some patients may require small supplemental doses of midazolam, in addition to dexmedetomidine, to achieve sufficient sedation for AFOI. Dexmedetomidine provides another AFOI option for sedation of patients with difficult airways.

  12. [Multicenter trial for optimization of bolus tracking settings and contrast material injection protocol in arterial dominant phase of dynamic computed tomography for diagnosis of hepatocellular carcinoma].

    Science.gov (United States)

    Yoshikawa, Shushi; Okada, Masahiro; Kondo, Hiroshi; Sou, Hironobu; Murakami, Takamichi; Kanematsu, Masayuki; Ichikawa, Tomoaki; Hayakawa, Akiko; Shiosakai, Kazuhito; Awai, Kazuo; Yoshimitsu, Kengo; Yamashita, Yasuyuki

    2014-08-01

    Alongside current improvements in the performance of computer tomography (CT) systems, there has been an increase in the use of bolus tracking (BT) to acquire arterial dominant phase images for dynamic CT at optimal timing for characterization of liver focal lesions. However, optimal BT settings have not been established. In the present study, methods of contrast enhancement and BT setting values were evaluated using a multicenter post-marketing surveillance study on contrast media used in patients with chronic hepatitis and/or cirrhosis who had undergone liver dynamic CT for diagnosis of hepatocellular carcinoma, conducted by Daiichi Sankyo Co., Ltd. The results suggested the contrast injection method to be clinically useful if the amount of iodine per kilogram of body weight is set at 600 mg/kg and the injection duration at 30 s. To achieve a good arterial dominant scan under conditions where the injection duration is fixed at 30 s or the average injection duration is 34 s using the fixed injection rate method, the scan delay time should ideally to be set to longer than 13 s. If using the BT method, we recommend that the BT settings should be revalidated in reference to our results.

  13. Immunogenicity and safety of trivalent inactivated influenza vaccine: a randomized, double-blind, multi-center, phase 3 clinical trial in a vaccine-limited country.

    Science.gov (United States)

    Song, Joon Young; Cheong, Hee Jin; Woo, Heung Jeong; Wie, Seong-Heon; Lee, Jin-Soo; Chung, Moon-Hyun; Kim, Yang Ree; Jung, Sook In; Park, Kyung-Hwa; Kim, Tae Hyong; Uh, Soo-Taek; Kim, Woo Joo

    2011-02-01

    Influenza vaccines are the primary method for controlling influenza and its complications. This study was conducted as a phase 3, randomized, double-blind, controlled, multi-center trial at seven university hospitals to evaluate the immunogenicity and safety of an inactivated, split, trivalent influenza vaccine (GC501, Green Cross Corporation, Yongin, Korea), which was newly manufactured in Korea in 2008. Between September 21 and 26, a total of 329 healthy subjects were recruited for the immunogenicity analysis, while 976 subjects were enrolled for the safety analysis. The GC501 vaccine met both FDA and EMEA criteria with ≥ 80% of subjects achieving post-vaccination titers ≥ 40 for all three subtypes, even in the elderly. The vaccine was well tolerated with only mild systemic and local adverse events. In summary, GC501 showed excellent immunogenicity and a good safety profile in both young adults and the elderly. The licensure of GC501 might be an important basis in preparation for the future influenza pandemic.

  14. A multicenter, randomized, double-blind, controlled phase 3 trial of fixed-dose brexpiprazole for the treatment of adults with acute schizophrenia.

    Science.gov (United States)

    Kane, John M; Skuban, Aleksandar; Ouyang, John; Hobart, Mary; Pfister, Stephanie; McQuade, Robert D; Nyilas, Margaretta; Carson, William H; Sanchez, Raymond; Eriksson, Hans

    2015-05-01

    The objective of this study was to evaluate the efficacy, safety and tolerability of brexpiprazole versus placebo in adults with acute schizophrenia. This was a 6-week, multicenter, placebo-controlled double-blind phase 3 study. Patients with acute schizophrenia were randomized to brexpiprazole 1, 2 or 4 mg, or placebo (2:3:3:3) once daily. The primary endpoint was changed from baseline at week 6 in Positive and Negative Syndrome Scale (PANSS) total score; the key secondary endpoint was Clinical Global Impressions-Severity (CGI-S) at week 6. Brexpiprazole 4 mg showed statistically significant improvement versus placebo (treatment difference: -6.47, p=0.0022) for the primary endpoint. Improvement compared with placebo was also seen for the key secondary endpoint (treatment difference: -0.38, p=0.0015), and on multiple secondary efficacy outcomes. Brexpiprazole 1 and 2mg also showed numerical improvements versus placebo, although p>0.05. The most common treatment-emergent adverse events were headache, insomnia and agitation; incidences of akathisia were lower in the brexpiprazole treatment groups (4.2%-6.5%) versus placebo (7.1%). Brexpiprazole treatment was associated with moderate weight gain at week 6 (1.23-1.89 kg versus 0.35 kg for placebo); there were no clinically relevant changes in laboratory parameters and vital signs. In conclusion, brexpiprazole 4 mg is an efficacious and well-tolerated treatment for acute schizophrenia in adults. Clinical Trials.gov NCT01393613; BEACON trial.

  15. A randomised, open-label, comparative study of tranexamic acid microinjections and tranexamic acid with microneedling in patients with melasma

    Directory of Open Access Journals (Sweden)

    Leelavathy Budamakuntla

    2013-01-01

    Full Text Available Background: Melasma is a common cause of facial hyperpigmentation with significant cosmetic deformity. Although several treatment modalities are available, none is satisfactory. Aim: To compare the therapeutic efficacy and safety of tranexamic acid (TA microinjections versus tranexamic acid with microneedling in melasma. Materials and Methods: This is a prospective, randomised, open-label study with a sample size of 60; 30 in each treatment arms. Thirty patients were administered with localised microinjections of TA in one arm, and other 30 with TA with microneedling. The procedure was done at monthly intervals (0, 4 and 8 weeks and followed up for three consecutive months. Clinical images were taken at each visit including modified Melasma Area Severity Index MASI scoring, patient global assessment and physician global assessment to assess the clinical response. Results: In the microinjection group, there was 35.72% improvement in the MASI score compared to 44.41% in the microneedling group, at the end of third follow-up visit. Six patients (26.09% in the microinjections group, as compared to 12 patients (41.38% in the microneedling group, showed more than 50% improvement. However, there were no major adverse events observed in both the treatment groups. Conclusions: On the basis of these results, TA can be used as potentially a new, effective, safe and promising therapeutic agent in melasma. The medication is easily available and affordable. Better therapeutic response to treatment in the microneedling group could be attributed to the deeper and uniform delivery of the medication through microchannels created by microneedling.

  16. A Randomised, Open-label, Comparative Study of Tranexamic Acid Microinjections and Tranexamic Acid with Microneedling in Patients with Melasma

    Science.gov (United States)

    Budamakuntla, Leelavathy; Loganathan, Eswari; Suresh, Deepak Hurkudli; Shanmugam, Sharavana; Suryanarayan, Shwetha; Dongare, Aparna; Venkataramiah, Lakshmi Dammaningala; Prabhu, Namitha

    2013-01-01

    Background: Melasma is a common cause of facial hyperpigmentation with significant cosmetic deformity. Although several treatment modalities are available, none is satisfactory. Aim: To compare the therapeutic efficacy and safety of tranexamic acid (TA) microinjections versus tranexamic acid with microneedling in melasma. Materials and Methods: This is a prospective, randomised, open-label study with a sample size of 60; 30 in each treatment arms. Thirty patients were administered with localised microinjections of TA in one arm, and other 30 with TA with microneedling. The procedure was done at monthly intervals (0, 4 and 8 weeks) and followed up for three consecutive months. Clinical images were taken at each visit including modified Melasma Area Severity Index MASI scoring, patient global assessment and physician global assessment to assess the clinical response. Results: In the microinjection group, there was 35.72% improvement in the MASI score compared to 44.41% in the microneedling group, at the end of third follow-up visit. Six patients (26.09%) in the microinjections group, as compared to 12 patients (41.38%) in the microneedling group, showed more than 50% improvement. However, there were no major adverse events observed in both the treatment groups. Conclusions: On the basis of these results, TA can be used as potentially a new, effective, safe and promising therapeutic agent in melasma. The medication is easily available and affordable. Better therapeutic response to treatment in the microneedling group could be attributed to the deeper and uniform delivery of the medication through microchannels created by microneedling. PMID:24163529

  17. Open-label atomoxetine for attention-deficit/ hyperactivity disorder symptoms associated with high-functioning pervasive developmental disorders.

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    Posey, David J; Wiegand, Ryan E; Wilkerson, Jennifer; Maynard, Melissa; Stigler, Kimberly A; McDougle, Christopher J

    2006-10-01

    The aim of this study was to conduct an initial evaluation of the efficacy of atomoxetine for attention-deficit/hyperactivity disorder (ADHD) symptoms in children with pervasive developmental disorders (PDDs). Children with PDDs and a nonverbal IQ of >or=70 received atomoxetine (target dose 1.2-1.4 mg/kg/day) during the course of an 8-week, open-label, prospective study. Standardized assessments of efficacy and tolerability were collected at regular intervals during the trial. Sixteen children and adolescents (mean age 7.7 +/- 2.2 years, age range 6-14 years) with autistic disorder (n = 7), Asperger's disorder (n = 7), or PDD not otherwise specified (n = 2) received atomoxetine (mean dose 1.2 +/- 0.3 mg/kg/day). Twelve participants (75%) were rated as "much" or "very much improved" on the Clinical Global Impressions-Improvement scale. The most significant improvement was seen in the area of ADHD symptoms as measured by the SNAP-IV and Aberrant Behavior Checklist (effect size = 1.0-1.9). Improvements of lesser magnitude (effect size = 0.4-1.1) were seen in irritability, social withdrawal, stereotypy, and repetitive speech. There were no significant changes on the Conners' Continuous Performance Test. Atomoxetine was well tolerated with the exception of 2 participants (13 %) who stopped medication due to irritability. Weight decreased by a mean of 0.8 kg during the 8-week trial. Placebo-controlled studies are indicated to determine atomoxetine's efficacy for ADHD symptoms in PDDs.

  18. Single-center open-label randomized study of anemia management improvement in ESRD patients with secondary hyperparathyroidism

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    Bellasi Antonio

    2016-04-01

    Full Text Available Whether anemia and mineral bone abnormalities (chronic kidney disease–mineral bone disorder [CKD-MBD] are associated still remains to be elucidated. Both anemia and CKD-MBD have been associated with adverse cardiovascular outcome and poor quality of life. However, recent evidence suggests that use of large doses of erythropoietin-stimulating agents (ESAs to correct hemoglobin (Hb may be detrimental in CKD. The Optimal Anemia Treatment in End Stage Renal Disease (ESRD (Optimal ESRD Treatment study will assess whether lowering of parathyroid hormone (PTH is associated with a reduction in ESA consumption. The Optimal ESRD Treatment study is a pilot single-center open-label study with blinded end point (a prospective randomized open blinded end-point [PROBE] design enrolling 50 patients on maintenance dialysis. Eligible patients with intact PTH (iPTH 300-540 pg/mL and Hb 10-11.5 g/dL will be randomized 1:1 to strict PTH control (150-300 pg/mL versus standard care (PTH range 300-540 pg/mL. Available drugs for CKD-MBD and anemia treatment will be managed by the attending physician to maintain the desired levels of PTH (according to study arm allocation and Hb (10-11.5 g/dL. Echocardiographic data for cardiac structure and function as well as arterial stiffness will be assessed at study inception and completion. The Optimal ESRD Treatment study should shed light on the complicated interplay of anemia and CKD-MBD and on the feasibility of clinical trials in this domain. The study results are expected in the spring of 2017.

  19. Treatment of asymptomatic vaginal candidiasis in pregnancy to prevent preterm birth: an open-label pilot randomized controlled trial

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    Rickard Kristen

    2011-03-01

    Full Text Available Abstract Background Although the connection between ascending infection and preterm birth is undisputed, research focused on finding effective treatments has been disappointing. However evidence that eradication of Candida in pregnancy may reduce the risk of preterm birth is emerging. We conducted a pilot study to assess the feasibility of conducting a large randomized controlled trial to determine whether treatment of asymptomatic candidiasis in early pregnancy reduces the incidence of preterm birth. Methods We used a prospective, randomized, open-label, blinded-endpoint (PROBE study design. Pregnant women presenting at Candida were randomized to 6-days of clotrimazole vaginal pessaries (100mg or usual care (screening result is not revealed, no treatment. The primary outcomes were the rate of asymptomatic vaginal candidiasis, participation and follow-up. The proposed primary trial outcome of spontaneous preterm birth Results Of 779 women approached, 500 (64% participated in candidiasis screening, and 98 (19.6% had asymptomatic vaginal candidiasis and were randomized to clotrimazole or usual care. Women were not inconvenienced by participation in the study, laboratory testing and medication dispensing were problem-free, and the follow-up rate was 99%. There was a tendency towards a reduction in spontaneous preterm birth among women with asymptomatic candidiasis who were treated with clotrimazole RR = 0.33, 95%CI 0.04-3.03. Conclusions A large, adequately powered, randomized trial of clotrimazole to prevent preterm birth in women with asymptomatic candidiasis is both feasible and warranted. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR: ACTRN12609001052224

  20. Gatifloxacin versus ofloxacin for the treatment of uncomplicated enteric fever in Nepal: an open-label, randomized, controlled trial.

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    Samir Koirala

    Full Text Available BACKGROUND: Fluoroquinolones are the most commonly used group of antimicrobials for the treatment of enteric fever, but no direct comparison between two fluoroquinolones has been performed in a large randomised trial. An open-label randomized trial was conducted to investigate whether gatifloxacin is more effective than ofloxacin in the treatment of uncomplicated enteric fever caused by nalidixic acid-resistant Salmonella enterica serovars Typhi and Paratyphi A. METHODOLOGY AND PRINCIPAL FINDINGS: Adults and children clinically diagnosed with uncomplicated enteric fever were enrolled in the study to receive gatifloxacin (10 mg/kg/day in a single dose or ofloxacin (20 mg/kg/day in two divided doses for 7 days. Patients were followed for six months. The primary outcome was treatment failure in patients infected with nalidixic acid resistant isolates. 627 patients with a median age of 17 (IQR 9-23 years were randomised. Of the 218 patients with culture confirmed enteric fever, 170 patients were infected with nalidixic acid-resistant isolates. In the ofloxacin group, 6 out of 83 patients had treatment failure compared to 5 out of 87 in the gatifloxacin group (hazard ratio [HR] of time to failure 0.81, 95% CI 0.25 to 2.65, p = 0.73. The median time to fever clearance was 4.70 days (IQR 2.98-5.90 in the ofloxacin group versus 3.31 days (IQR 2.29-4.75 in the gatifloxacin group (HR = 1.59, 95% CI 1.16 to 2.18, p = 0.004. The results in all blood culture-confirmed patients and all randomized patients were comparable. CONCLUSION: Gatifloxacin was not superior to ofloxacin in preventing failure, but use of gatifloxacin did result in more prompt fever clearance time compared to ofloxacin. TRIAL REGISTRATION: ISRCTN 63006567 (www.controlled-trials.com.

  1. Combined gemcitabine and S-1 chemotherapy for treating unresectable hilar cholangiocarcinoma: a randomized open-label clinical trial.

    Science.gov (United States)

    Li, Hao; Zhang, Zheng-Yun; Zhou, Zun-Qiang; Guan, Jiao; Tong, Da-Nian; Zhou, Guang-Wen

    2016-05-03

    Although the combination of cisplatin and gemcitabine (GEM) is considered the standard first-line chemotherapy against unresectable hilar cholangiocarcinoma (HC), its efficacy is discouraging. The present randomized open-label clinical trial aimed to evaluate the efficacy and safety of the GEM plus S-1 (GEM-S-1) combination against unresectable HC. Twenty-five patients per group were randomly assigned to receive GEM, S-1 or GEM-S-1. Neutropenia (56%) and leukopenia (40%) were the most common chemotherapy-related toxicities in the GEM-S-1 group. Median overall survival (OS) in the GEM-S-1, GEM and S-1 groups was 11, 10 and 6 months, respectively. GEM plus S-1 significantly improved OS compared to S-1 monotherapy (OR=0.68; 95%CI, 0.50-0.90; P=0.008). Median progression-free survival (PFS) times in the GEM-S-1, GEM and S-1 groups were 4.90, 3.70 and 1.60 months, respectively. GEM plus S-1 significantly improved PFS compared to S-1 monotherapy (OR=0.50; 95%CI, 0.27-0.91; P=0.024). Response rates were 36%, 24% and 8% in the GEM-S-1, GEM and S-1 groups, respectively. A statistically significant difference was found in response rates between the gemcitabine-S-1 and S-1 groups (36% vs 8%, P=0.017). Patients with CA19-9S-1 provides a better OS, PFS and response rate than S-1 monotherapy, but it did not significantly differ from GEM monotherapy. (ChiCTR-TRC-14004733).

  2. An open-label study of anidulafungin for the treatment of candidaemia/invasive candidiasis in Latin America.

    Science.gov (United States)

    Nucci, Marcio; Colombo, Arnaldo L; Petti, Marco; Magana, Martin; Abreu, Paula; Schlamm, Haran T; Sanchez, Sonia P

    2014-01-01

    Incidence and mortality of candidaemia/invasive candidiasis (C/IC) is relatively high in Latin America versus North America and Europe. To assess efficacy and safety of intravenous (IV) anidulafungin in Latin American adults with documented C/IC. All patients in this open-label study received initial IV anidulafungin with optional step-down to oral voriconazole after 5 days; total treatment duration was 14-42 days. The primary endpoint was global response (clinical + microbiological response) at end of treatment (EOT); missing/indeterminate responses were failures. The study enrolled 54 patients; 44 had confirmed C/IC within 96 h before study entry and comprised the modified intent-to-treat population. Global response at EOT was 59.1% (95% CI: 44.6, 73.6), with 13 missing/indeterminate assessments. Thirty-day all-cause mortality was 43.1%. Fourteen patients (31.8%) were able to step-down to oral voriconazole; these patients had lower baseline acute physiological assessment and chronic health evaluation (APACHE) II scores and were less likely to have solid tumours or previous abdominal surgery. Anidulafungin was generally well tolerated with few treatment-related adverse events. Anidulafungin was associated with relatively low response rates influenced by a high rate of missing/indeterminate assessments and mortality comparable to other recent candidaemia studies in Latin America. In a subset of patients with lower APACHE II scores, short-course anidulafungin followed by oral voriconazole was successful.

  3. Effects of quetiapine and olanzapine in patients with psychosis and violent behavior: a pilot randomized, open-label, comparative study

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    Gobbi G

    2014-05-01

    Full Text Available Gabriella Gobbi,1,2 Stefano Comai,1 Guy Debonnel1,2,† 1Neurobiological Psychiatric Unit, Department of Psychiatry, McGill University and McGill University Health Center, 2Institut Philippe Pinel, Department of Psychiatry, Université de Montréal, Montréal, QC, Canada †Guy Debonnel passed away on November 4, 2006 Objective: Patients suffering from psychosis are more likely than the general population to commit aggressive acts, but the therapeutics of aggressive behavior are still a matter of debate. Methods: This pilot randomized, open-label study compared the efficacy of quetiapine versus olanzapine in reducing impulsive and aggressive behaviors (primary endpoints and psychotic symptoms (secondary endpoints from baseline to days 1, 7, 14, 28, 42, 56, and 70, in 15 violent schizophrenic patients hospitalized in a maximum-security psychiatric hospital. Results: Quetiapine (525±45 mg and olanzapine (18.5±4.8 mg were both efficacious in reducing Impulsivity Rating Scale from baseline to day 70. In addition, both treatments reduced the Brief Psychiatric Rating Scale, Positive and Negative Syndrome Scale, and Clinical Global Impression Scale scores at day 70 compared to baseline, and no differences were observed between treatments. Moreover, quetiapine, but not olanzapine, yielded an improvement of depressive symptoms in the items “depression” in Brief Psychiatric Rating Scale and “blunted affect” in Positive and Negative Syndrome Scale. Modified Overt Aggression Scale scores were also decreased from baseline to the endpoint, but due to the limited number of patients, it was not possible to detect a significant difference. Conclusion: In this pilot study, quetiapine and olanzapine equally decreased impulsive and psychotic symptoms after 8 weeks of treatment. Double-blind, large studies are needed to confirm the validity of these two treatments in highly aggressive and violent schizophrenic patients. Keywords: schizophrenia, aggression

  4. The efficacy of the modified Atkins diet in North Sea Progressive Myoclonus Epilepsy: an observational prospective open-label study.

    Science.gov (United States)

    van Egmond, Martje E; Weijenberg, Amerins; van Rijn, Margreet E; Elting, Jan Willem J; Gelauff, Jeannette M; Zutt, Rodi; Sival, Deborah A; Lambrechts, Roald A; Tijssen, Marina A J; Brouwer, Oebele F; de Koning, Tom J

    2017-03-07

    North Sea Progressive Myoclonus Epilepsy is a rare and severe disorder caused by mutations in the GOSR2 gene. It is clinically characterized by progressive myoclonus, seizures, early-onset ataxia and areflexia. As in other progressive myoclonus epilepsies, the efficacy of antiepileptic drugs is disappointingly limited in North Sea Progressive Myoclonus Epilepsy. The ketogenic diet and the less restrictive modified Atkins diet have been proven to be effective in other drug-resistant epilepsy syndromes, including those with myoclonic seizures. Our aim was to evaluate the efficacy of the modified Atkins diet in patients with North Sea Progressive Myoclonus Epilepsy. Four North Sea Progressive Myoclonus Epilepsy patients (aged 7-20 years) participated in an observational, prospective, open-label study on the efficacy of the modified Atkins diet. Several clinical parameters were assessed at baseline and again after participants had been on the diet for 3 months. The primary outcome measure was health-related quality of life, with seizure frequency and blinded rated myoclonus severity as secondary outcome measures. Ketosis was achieved within 2 weeks and all patients completed the 3 months on the modified Atkins diet. The diet was well tolerated by all four patients. Health-related quality of life improved considerably in one patient and showed sustained improvement during long-term follow-up, despite the progressive nature of the disorder. Health-related quality of life remained broadly unchanged in the other three patients and they did not continue the diet. Seizure frequency remained stable and blinded rating of their myoclonus showed improvement, albeit modest, in all patients. This observational, prospective study shows that some North Sea Progressive Myoclonus Epilepsy patients may benefit from the modified Atkins diet with sustained health-related quality of life improvement. Not all our patients continued on the diet, but nonetheless we show that the modified

  5. Sertraline and rapid eye movement sleep without atonia: an 8-week, open-label study of depressed patients.

    Science.gov (United States)

    Zhang, Bin; Hao, Yanli; Jia, Fujun; Tang, Yi; Li, Xueli; Liu, Wuhan; Arnulf, Isabelle

    2013-12-02

    Previous studies have reported that selective serotonin reuptake inhibitors (SSRIs) may induce or exacerbate rapid eye movement (REM) sleep without atonia (RSWA) and increase the risk of developing REM sleep behavior disorder (RBD). However, most of these studies are retrospective and cross-sectional and employed small sample sizes and a mixture of SSRIs. In this 8-week open-label trial of sertraline in depressed patients (n = 31), depressed patients were administered 50mg sertraline at 8 am on the 1st day and subsequently titrated up to a maximum of 200mg/day. All patients underwent repeated video-polysomnography (vPSG) (baseline, 1st day, 14th day, 28th day, and 56th day). Both tonic (submental) and phasic (submental and anterior tibialis) RSWA events were visually counted. Tonic RSWA increased from 3.2 ± 1.8% at baseline to 5.1 ± 2.3% on the 1st day and 10.4 ± 2.7% on the 14th day; after that, measurements were stable until the 56th day. A similar profile was observed for phasic RSWA. The increases in tonic RSWA (r = 0.56, P = 0.004) and phasic RSWA (submental: r = -0.51, P = 0.02; anterior tibialis: r = 0.41, P = 0.04) were correlated with the degree of the prolonging of REM latency. All of RSWAs were not correlated with patients' demographic and clinical characteristics. Sertraline may induce or exacerbate RSWA. In contrast to idiopathic RBD, sertraline-related RSWA had the specific characteristics of being correlated with the degree of the prolonging of REM latency and no predominance of male sex and elder age, suggesting different pathophysiological mechanisms. The antidepressant-related RSWA should be a potential public health problem in the depressed patients.

  6. Eldecalcitol improves muscle strength and dynamic balance in postmenopausal women with osteoporosis: an open-label randomized controlled study.

    Science.gov (United States)

    Saito, Kimio; Miyakoshi, Naohisa; Matsunaga, Toshiki; Hongo, Michio; Kasukawa, Yuji; Shimada, Yoichi

    2016-09-01

    The antifracture efficacy of vitamin D in osteoporosis is due to its direct action on bones and indirect extraskeletal effects to prevent falls. Eldecalcitol is an analog of active vitamin D3 that improves bone mineral density and reduces the risk of osteoporotic fractures. However, the effects of eldecalcitol on muscle strength and static and dynamic postural balance are unclear. In this open-label randomized controlled study, we assessed the effects of eldecalcitol on muscle strength and static and dynamic postural balance in 50 postmenopausal women (mean age 74 years) with osteoporosis treated with bisphosphonate. Participants were randomly divided into a bisphosphonate group (alendronate at 35 mg/week; n = 25) or an eldecalcitol group (eldecalcitol at 0.75 μg/day and alendronate at 35 mg/week; n = 25) and were followed up for 6 months. Trunk muscle strength, including back extensor strength and iliopsoas muscle strength, was measured. Static standing balance was evaluated and the one leg standing test was performed to assess static postural balance. Dynamic sitting balance was evaluated and the 10-m walk test, functional reach test, and timed up and go test were performed to assess dynamic postural balance. At 6 months, there were no significant changes in any measure of muscle strength or balance in the bisphosphonate group, whereas eldecalcitol significantly increased back extensor strength (p = 0.012) and iliopsoas muscle strength (p = 0.035). Eldecalcitol also significantly improved findings on the timed up and go test (p = 0.001) and dynamic sitting balance (p = 0.015) at 6 months. These results with eldecalcitol may have an impact on prevention of falls.

  7. Agomelatine versus Sertraline: An Observational, Open-labeled and 12 Weeks Follow-up Study on Efficacy and Tolerability

    Science.gov (United States)

    Akpınar, Esma; Cerit, Cem; Talas, Anıl; Tural, Ümit

    2016-01-01

    Objective In this open-labeled, 12 weeks follow-up study, we aimed to compare the efficacy and tolerability of agomelatine with sertraline Methods The outpatients of adult psychiatry clinic who have a new onset of depression and diagnosed as ‘major depressive episode’ by clinician according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition and prescribed agomelatine (25 mg/day) or sertraline (50 mg/day) were included in the study. Results The decline of mean Montgomery-Asberg Depression Rating Scale (MADRS) scores of agomelatine group was significantly higher than the sertraline group at the end of 2nd week; however, the difference was not significant at the end of 3 months. Mean Clinical Global Impression-Improvement scale (CGI-I) scores of agomelatine group was lower than sertraline group at first week. Mean CGI-Severity scale and CGI-I scores were favour to sertraline group at the end of the study. Remission rates were 46.7% for sertraline group and 33.3% for agomelatine group while response rates were 76.7% for both groups. Any patient from agomelatine group dropped-out due to adverse effects. The amount of side effects was also less with agomelatine. Conclusion Agomelatine has a rapid onset efficacy on depressive symptoms and this can be beneficial for some critical cases. Considering MADRS scores, agomelatine seems to have similar efficacy with sertraline but we also point the need for long term studies since CGI scores were favour to sertraline group at the end of the study. Agomelatine has a favourable tolerability profile both in terms of discontinuation and the amount of side effects compared to sertraline. PMID:27776387

  8. An open label follow-up study on amisulpride in the add-on treatment of bipolar I patients

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    Hardoy Maria

    2006-08-01

    Full Text Available Abstract Background Atypical antipsychotics are widely used in the treatment of bipolar disorders. Amisulpride is an atypical antipsychotic that has been proven to be effective in treatment of schizophrenia, major depressive disorder and, more recently, acute mania. At the moment, however, no study has assessed the effectiveness of this compound in maintenance therapy of bipolar disorders. The purpose of this study was to assess the long-term effectiveness of amisulpride in combination with standard treatments in patients with bipolar I disorder who have shown inadequate responses to ongoing standard therapies. Methods The study enrolled fourteen bipolar I outpatients, not responding to ongoing standard therapy. Three patients discontinued treatment but 11 were followed-up for 11.7 ± 8.2 months before (range 3–24 months and 5.2 ± 2.7 months after the introduction of amisulpride (range 3–9 months. Relapse rates before and during treatment with amisulpride were calculated in accordance to an increase of 1 or more in Clinical Global Impressions Scale-Bipolar Version (CGI-BP score that was accompanied by a change in therapy or to an exacerbation of the symptoms that required hospitalization. Results A statistically significant decrease in overall relapse rate was observed during the period of amisulpride therapy compared with months previous to the introduction of amisulpride. The relative risk of relapse in the absence of amisulpride therapy was 3.1 (χ2 = 4.2, P Discussion and conclusion This open-label study suggests that long-term therapy with amisulpride may benefit patients by improving global symptoms of bipolar disorder and reducing the rate of manic/mixed relapses. Large, randomized, double-blind, placebo-controlled studies are needed to explore the benefits of adding long-term amisulpride to standard therapies for bipolar disorder.

  9. Anti-tumour effects of lanreotide for pancreatic and intestinal neuroendocrine tumours: the CLARINET open-label extension study.

    Science.gov (United States)

    Caplin, Martyn E; Pavel, Marianne; Ćwikła, Jarosław B; Phan, Alexandria T; Raderer, Markus; Sedláčková, Eva; Cadiot, Guillaume; Wolin, Edward M; Capdevila, Jaume; Wall, Lucy; Rindi, Guido; Langley, Alison; Martinez, Séverine; Gomez-Panzani, Edda; Ruszniewski, Philippe

    2016-03-01

    In the CLARINET study, lanreotide Autogel (depot in USA) significantly prolonged progression-free survival (PFS) in patients with metastatic pancreatic/intestinal neuroendocrine tumours (NETs). We report long-term safety and additional efficacy data from the open-label extension (OLE). Patients with metastatic grade 1/2 (Ki-67 ≤ 10%) non-functioning NET and documented baseline tumour-progression status received lanreotide Autogel 120 mg (n = 101) or placebo (n = 103) for 96 weeks or until death/progressive disease (PD) in CLARINET study. Patients with stable disease (SD) at core study end (lanreotide/placebo) or PD (placebo only) continued or switched to lanreotide in the OLE. In total, 88 patients (previously: lanreotide, n = 41; placebo, n = 47) participated: 38% had pancreatic, 39% midgut and 23% other/unknown primary tumours. Patients continuing lanreotide reported fewer adverse events (AEs) (all and treatment-related) during OLE than core study. Placebo-to-lanreotide switch patients reported similar AE rates in OLE and core studies, except more diarrhoea was considered treatment-related in OLE (overall diarrhoea unchanged). Median lanreotide PFS (core study randomisation to PD in core/OLE; n=101) was 32.8 months (95% CI: 30.9, 68.0). A sensitivity analysis, addressing potential selection bias by assuming that patients with SD on lanreotide in the core study and not entering the OLE (n=13) had PD 24 weeks after last core assessment, found median PFS remaining consistent: 30.8 months (95% CI: 30.0, 31.3). Median time to further PD after placebo-to-lanreotide switch (n=32) was 14.0 months (10.1; not reached). This OLE study suggests long-term treatment with lanreotide Autogel 120 mg maintained favourable safety/tolerability. CLARINET OLE data also provide new evidence of lanreotide anti-tumour benefits in indolent and progressive pancreatic/intestinal NETs. © 2016 The authors.

  10. A randomized, open-label study of sirolimus versus cyclosporine in primary de novo renal allograft recipients.

    Science.gov (United States)

    Flechner, Stuart M; Gurkan, Alihan; Hartmann, Anders; Legendre, Christophe M; Russ, Graeme R; Campistol, Josep M; Schena, Francesco P; Hahn, Carolyn M; Li, Huihua; Korth-Bradley, Joan M; Tai, Sandi See; Schulman, Seth L

    2013-05-27

    Despite a decreased incidence of acute rejection and early renal allograft loss due to calcineurin inhibitors (CNIs) in transplant recipients, nephrotoxicity associated with long-term CNI use remains an important issue. This study evaluated whether a CNI-free regimen, including sirolimus, mycophenolate mofetil, corticosteroids, and anti-interleukin-2 receptor antibody induction, results in improved long-term renal function. This open-label, randomized, parallel group, comparative study in primary de novo renal transplant recipients was planned for 48 months but terminated early because of high acute rejection rates in the sirolimus arm. Enrollment was stopped after ≈12 months, with 475 transplanted patients randomized (2:1) to sirolimus (n=314) or cyclosporine A (CsA) treatment (n=161). Mean length of follow-up after transplantation was 190 days; this article focuses on available data through 6 months. Mean±SD on-therapy Nankivell-calculated glomerular filtration rate was not significantly different between the sirolimus (69.1±18.7 mL/min) and CsA (66.0±15.2 mL/min) treatment groups. Occurrence and length of delayed graft function was not significantly different between groups. Patients in the sirolimus group experienced numerically lower survival rates (96.9% vs. 99.4%; P=0.14), with nine deaths reported with sirolimus and one with CsA; higher rates of biopsy-confirmed acute rejection (21.4% vs. 6.1%; P<0.001); and higher rates of discontinuations due to adverse events (17.4% vs. 6.8%; P=0.001). A sirolimus-based, CNI-free immunosuppressive regimen, when used with mycophenolate mofetil, corticosteroids, and anti-interleukin-2 receptor antibody induction, was associated with high rates of biopsy-confirmed acute rejection compared with CsA-based immunosuppression and is not recommended.

  11. Preliminary open-label clinical evaluation of the soothing and reepithelialization properties of a novel topical formulation for rosacea

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    Sparavigna A

    2014-10-01

    Full Text Available Adele Sparavigna, Beatrice Tenconi, Ileana De Ponti Derming Srl, Monza, Italy Background: Rosacea is a common, incurable skin barrier disorder characterized by relapses and remissions. Purpose: To evaluate the efficacy of Farmaka Rosacea Cream (FRC, a novel topical formulation for rosacea. Methods: This single-center, open-label pilot study comprised a single-dose substudy in 20 healthy subjects and a long-term, repeat-dose substudy in 22 subjects with rosacea. The 2-hour, controlled, single-dose substudy assessed the soothing and reepithelialization properties of FRC after stripping-induced erythema based on the erythema index, transepidermal water loss, skin hydration, and clinical assessments of erythema. In the long-term substudy, subjects applied FRC twice daily for 8 weeks. Clinical assessments included vascular and pigmentary homogeneity and erythema and hemoglobin indices. Subjects completed questionnaires to assess FRC efficacy and cosmetic acceptability. Results: Greater reductions were seen in FRC-treated areas compared with untreated areas for the erythema index (-16% versus -8%; P<0.001 and mean transepidermal water loss (-35.8% versus -10.1%; P<0.001 30 minutes after stripping. Significant improvements over untreated areas were maintained 2 hours after stripping. Skin hydration and clinical erythema assessments also indicated that FRC soothed rosacea symptoms and promoted skin reepithelialization. Erythema and hemoglobin indices were significantly reduced from baseline after 4 and 8 weeks of treatment. Clinically assessed parameters were significantly improved following FRC application. Subjects assessed FRC positively. Conclusion: Improvement of rosacea symptoms was noted with FRC application. The main film-forming ingredients of FRC (trehalose, cholesterol, ceramide, and fatty acids, combined with other soothing and calming ingredients and ultraviolet filters, could explain its efficacy. Keywords: rosacea, erythema, skin

  12. Safety and efficacy of an olive oil-based triple-chamber bag for parenteral nutrition: a prospective, randomized, multi-center clinical trial in China

    OpenAIRE

    Jia, Zhen-Yi; Yang, Jun; XIA, Yang; Tong, Da-Nian; Gary P. Zaloga; Qin, Huan-Long; ,

    2015-01-01

    Background Small studies suggest differences in efficacy and safety exist between olive oil-based (OLIVE) and soybean oil-based (SOYBEAN) parenteral nutrition regimens in hospitalized adult patients. This large, prospective, randomized (1:1), open-label, multi-center, noninferiority study compared the delivery, efficacy, and safety of OLIVE (N = 226) with SOYBEAN (N = 232) in Chinese adults (≥18 years) admitted to a surgical service for whom parenteral nutrition was required. Methods Treatmen...

  13. Stereotactic Body Radiation Therapy for Prostate Cancer: Review of Experience of a Multicenter Phase I/II Dose Escalation Study

    Directory of Open Access Journals (Sweden)

    D. Nathan W. Kim

    2014-11-01

    Full Text Available Introduction: Stereotactic body radiation therapy (SBRT is an area of active investigation for treatment of prostate cancer. In our phase I dose escalation study maximum tolerated dose was not reached, and subsequently phase II study has been completed. The purpose of this article is to review our experiences of dose escalated SBRT for localized prostate cancer. Methods and Materials: Patients enrolled to phase I/II study from 2006-2011 were reviewed. Prescription dose groups were 45, 47.5 and 50 Gray (Gy in 5 fractions over 2.5 weeks. Toxicity and quality of life questionnaire data were collected and analyzed. Descriptive statistics were obtained in the form of means, medians, and ranges for the continuous variables, and frequencies and percentages for the categoric variables. Results: 91 patients were enrolled from five institutions. Median follow up for PSA evaluation was 42 months. PSA control remains at 99%. While the maximum tolerated dose was not reached in the phase I study, excess high grade rectal toxicity (10.6% was noted in the phase II study. The 13 patients treated to 50 Gy in the phase I study that did not have high grade rectal toxicity, in retrospect met these parameters and have not had further events on longer follow up. Conclusion: PSA control rate, even for patients with intermediate risk, is thus far excellent at these dose levels. This study provides a platform for exploration of SBRT based clinical trials aimed at optimizing outcome for intermediate and high risk patients. High grade toxicities specifically related to the rectum were observed in a small but meaningful minority at the highest dose level. Dose constraints based on physiologic parameters have been defined to mitigate this risk, and strategies to minimize rectal exposure to such doses are being explored.

  14. A Nutritional Formulation for Cognitive Performance in Mild Cognitive Impairment: A Placebo-Controlled Trial with an Open-Label Extension.

    Science.gov (United States)

    Remington, Ruth; Lortie, Jevin J; Hoffmann, Heather; Page, Robert; Morrell, Christopher; Shea, Thomas B

    2015-01-01

    Thirty-four individuals with mild cognitive impairment were randomized for 6 months to a nutraceutical formulation (NF: folate, alpha-tocopherol, B12, S-adenosyl methioinine, N-acetyl cysteine, acetyl-L-carnitine) or indistinguishable placebo, followed by a 6-month open-label extension in which all individuals received NF. The NF cohort improved in the Dementia Rating Scale (DRS; effect size >0.7) and maintained baseline performance in CLOX-1. The placebo cohort did not improve in DRS and declined in CLOX-1, but during the open-label extension improved in DRS and ceased declining in CLOX-1. These findings extend prior studies of NF efficacy for individuals without cognitive impairment and with Alzheimer's disease.

  15. A Randomized, Double-Blind, Single-Dose, Placebo-Controlled, Multicenter, Polysomnographic Study of Gabapentin in Transient Insomnia Induced by Sleep Phase Advance

    Science.gov (United States)

    Rosenberg, Russell P.; Hull, Steven G.; Lankford, D. Alan; Mayleben, David W.; Seiden, David J.; Furey, Sandy A.; Jayawardena, Shyamalie; Roth, Thomas

    2014-01-01

    Study Objectives: To evaluate the effects of single doses of gabapentin 250 and 500 mg on polysomnographic (PSG) and participant-reported sleep measures in a 5-h phase advance insomnia model. Methods: Adults reporting occasional disturbed sleep received gabapentin 500 mg (n = 125), 250 mg (n = 125), or placebo (n = 127) 30 min prior to bedtime and were in bed from 17:00 to 01:00, ∼5 h before their habitual bedtime. Sleep was assessed by PSG, post-sleep questionnaire, and the Karolinska Sleep Diary (KSD). Next-day residual effects (Digit Symbol Substitution Test [DSST] and Stanford Sleepiness Scale [SSS]) and tolerability were assessed. Results: Demographics were comparable among groups. Among PSG endpoints, wake after sleep onset (primary endpoint) (135.7 [placebo], 100.7 [250 mg], and 73.2 [500 mg] min) was significantly lower and total sleep time (TST) (311.4, 356.5, and 378.7 min) significantly greater in both gabapentin groups versus placebo. Latency to persistent sleep was not significantly different among groups. Percent slow wave sleep (12.6%, 15.4%, and 17.0%, respectively) was significantly greater and percent stage 1 (15.1%, 11.8%, and 10.8%, respectively) significantly lower relative to placebo. Gabapentin was associated with significantly higher values of KSD Sleep Quality Index and reported TST versus placebo; no other reported outcomes were significant. Neither gabapentin dose produced evidence of next-day residual effects as measured by DSST and SSS. Adverse events were infrequent (Rosenberg RP, Hull SG, Lankford DA, Mayleben DW, Seiden DJ, Furey SA, Jayawardena S, Roth T. A randomized, double-blind, single-dose, placebo-controlled, multicenter, polysomnographic study of gabapentin in transient insomnia induced by sleep phase advance. J Clin Sleep Med 2014;10(10):1093-1100. PMID:25317090

  16. Sustained effects of once-daily memantine treatment on cognition and functional communication skills in patients with moderate to severe Alzheimer's disease: results of a 16-week open-label trial.

    Science.gov (United States)

    Schulz, Jörg B; Rainer, Michael; Klünemann, Hans-Hermann; Kurz, Alexander; Wolf, Stefanie; Sternberg, Kati; Tennigkeit, Frank

    2011-01-01

    The present study evaluated the effects of once-daily memantine (20 mg) treatment on cognition and communication in patients with moderate to severe Alzheimer's disease (AD). In a multicenter, single-arm open-label study, outpatients diagnosed with AD (MMSE < 20; n = 97) were titrated from 5 mg to 20 mg once-daily memantine over 4 weeks. Once-daily memantine treatment (20 mg) was then continued for 8 weeks, followed by a 4-week wash-out period. The primary efficacy endpoint was the change from baseline in the Consortium to Establish a Registry for Alzheimer's Disease -Neuropsychological Battery (CERAD-NP) total score. Secondary efficacy endpoints included change from baseline in Functional Communication Language Inventory (FLCI) and ADCS-ADL19 total score, and the response from baseline in Clinical Global Impression of Change (CGI-C). The CERAD-NP total score improved significantly after 12 weeks of once-daily memantine treatment compared with baseline (5.9 ± 8.8; p < 0.0001). The FLCI total score improved significantly after 12 weeks compared with baseline (4.4 ± 6.8; p < 0.0001). These significant improvements were already observed after 4 and 8 weeks of once-daily memantine treatment and persisted after a 4-week wash-out period. ADCS-ADL19 total scores showed only slight increases from baseline, and CGI-C indicated that the majority of patients experienced an improvement or stabilization of the disease after 12 weeks. At least one Treatment-Emergent Adverse Event was reported by 38 (39.2%) patients. In patients with moderate to severe AD, once-daily memantine (20 mg) treatment significantly improved cognition and functional communication and was found to have a favorable safety and tolerability profile.

  17. A Prospective, Open Label, Observational Study to Assess the Safety and Efficacy of Herbal Cough Syrup Mykoff® in Patients Suffering from Cough of Varied Aetiologies

    OpenAIRE

    Mangesh Bhalerao; Pradip Awale; Abhijeet Sawle; Dhananjay Sangle; Devendra B Sonawane; Vilas Chavan

    2013-01-01

    A prospective, open label, observational study was conducted at general outpatient clinic to assess the safety and efficacy of herbal cough syrup Mykoff® in patients suffering from cough of varied aetiologies. The patients of either sex, age > 3yrs, suffering from cough due to common cold, mild to moderate upper respiratory tract infections, allergic cough and smoker’s cough were enrolled. The safety was evaluated by means of an analysis of adverse events. In addition, efficacy and tolerabili...

  18. A randomized, open-label trial of iron isomaltoside 1000 (Monofer®) compared with iron sucrose (Venofer®) as maintenance therapy in haemodialysis patients

    OpenAIRE

    Bhandari, Sunil; Kalra, Philip A.; Kothari, Jatin; Ambühl, Patrice M.; Christensen, Jeppe H.; Essaian, Ashot M.; Thomsen, Lars L.; Macdougall, Iain C.; Coyne, Daniel W.

    2015-01-01

    Background Iron deficiency anaemia is common in patients with chronic kidney disease, and intravenous iron is the preferred treatment for those on haemodialysis. The aim of this trial was to compare the efficacy and safety of iron isomaltoside 1000 (Monofer®) with iron sucrose (Venofer®) in haemodialysis patients. Methods This was an open-label, randomized, multicentre, non-inferiority trial conducted in 351 haemodialysis subjects randomized 2 : 1 to either iron isomaltoside 1000 (Group A) or...

  19. Ringer’s lactate, but not hydroxyethyl starch, prolongs the food intolerance time after major abdominal surgery; an open-labelled clinical trial

    OpenAIRE

    Li, Yuhong; He, Rui; Ying, Xiaojiang; Hahn, Robert

    2015-01-01

    Background: The infusion of large amounts of Ringers lactate prolongs the functional gastrointestinal recovery time and increases the number of complications after open abdominal surgery. We performed an open-labelled clinical trial to determine whether hydroxyethyl starch or Ringers lactate exerts these adverse effects when the surgery is performed by laparoscopy. Methods: Eighty-eight patients scheduled for major abdominal cancer surgery (83% by laparoscopy) received a first-line fluid trea...

  20. Metformin Treatment in Type 2 Diabetes in Pregnancy: An Active Controlled, Parallel-Group, Randomized, Open Label Study in Patients with Type 2 Diabetes in Pregnancy

    OpenAIRE

    2015-01-01

    Aims. To assess the effect of metformin and to compare it with insulin treatment in patients with type 2 diabetes in pregnancy in terms of perinatal outcome, maternal complications, additional insulin requirement, and treatment acceptability. Methods. In this randomized, open label study, 206 patients with type 2 diabetes in pregnancy who met the eligibility criteria were selected from the antenatal clinics. Insulin was added to metformin treatment when required, to maintain the target glycem...

  1. Evaluation of efficacy and tolerability of eperisone and thiocolchicoside in treatment of low back pain associated with muscle spasm: An open label, prospective, randomized controlled trial

    OpenAIRE

    Syed H. Maaz; Prakash N. Khandelwal; Shiraz M. Baig; Sudhakar M. Doifode; Ulhas M. Ghotkar

    2016-01-01

    Background: Low back pain has a high prevalence in adult population. Because of reflex muscle spasm, muscle relaxants are frequently used either alone or in combination with analgesics. Eperisone inhibits voltage gated sodium channels in brain stem and Thiocolchicoside acts via GABA-mediated mechanism to relax muscle spasm and relieves pain. Methods: This was a prospective; open labeled, randomized, two-arm, parallel group, controlled, clinical trial. 113 patients were randomised to two gr...

  2. 5% lidocaine medicated plaster versus pregabalin in post-herpetic neuralgia and diabetic polyneuropathy: an open-label, non-inferiority two-stage RCT study.

    Science.gov (United States)

    Baron, Ralf; Mayoral, Victor; Leijon, Göran; Binder, Andreas; Steigerwald, Ilona; Serpell, Michael

    2009-07-01

    To compare efficacy and safety of 5% lidocaine medicated plaster with pregabalin in patients with post-herpetic neuralgia (PHN) or painful diabetic polyneuropathy (DPN). This was a two-stage adaptive, randomized, open-label, multicentre, non-inferiority study. Data are reported from the initial 4-week comparative phase, in which adults with PHN or painful DPN received either topical 5% lidocaine medicated plaster applied to the most painful skin area or twice-daily pregabalin capsules titrated to effect according to the Summary of Product Characteristics. The primary endpoint was response rate at 4 weeks, defined as reduction averaged over the last three days from baseline of > or = 2 points or an absolute value of plaster and 61.5% receiving pregabalin were considered responders (corresponding numbers for the per protocol set, PPS: 65.3% vs. 62.0%). In PHN more patients responded to 5% lidocaine medicated plaster treatment than to pregabalin (PPS: 62.2% vs. 46.5%), while response was comparable for patients with painful DPN (PPS: 66.7% vs 69.1%). 30% and 50% reductions in NRS-3 scores were greater with 5% lidocaine medicated plaster than with pregabalin. Both treatments reduced allodynia severity. 5% lidocaine medicated plaster showed greater improvements in QoL based on EQ-5D in both PHN and DPN. PGIC and CGIC scores indicated greater improvement for 5% lidocaine medicated plaster treated patients with PHN. Improvements were comparable between treatments in painful DPN. Fewer patients administering 5% lidocaine medicated plaster experienced AEs (safety set, SAF: 18.7% vs. 46.4%), DRAEs (5.8% vs. 41.2%) and related discontinuations compared to patients taking pregabalin. 5% lidocaine medicated plaster showed better efficacy compared with pregabalin in patients with PHN. Within DPN, efficacy was comparable for both treatments. 5% lidocaine medicated plaster showed a favourable efficacy/safety profile with greater improvements in patient satisfaction and Qo

  3. Comparison of Doxycycline, Minocycline, Doxycycline plus Albendazole and Albendazole Alone in Their Efficacy against Onchocerciasis in a Randomized, Open-Label, Pilot Trial

    Science.gov (United States)

    Batsa, Linda; Ayisi-Boateng, Nana Kwame; Osei-Mensah, Jubin; Mubarik, Yusif; Konadu, Peter; Ricchiuto, Arcangelo; Fimmers, Rolf; Arriens, Sandra; Dubben, Bettina; Ford, Louise; Taylor, Mark; Hoerauf, Achim

    2017-01-01

    The search for new macrofilaricidal drugs against onchocerciasis that can be administered in shorter regimens than required for doxycycline (DOX, 200mg/d given for 4–6 weeks), identified minocycline (MIN) with superior efficacy to DOX. Further reduction in the treatment regimen may be achieved with co-administration with standard anti-filarial drugs. Therefore a randomized, open-label, pilot trial was carried out in an area in Ghana endemic for onchocerciasis, comprising 5 different regimens: the standard regimen DOX 200mg/d for 4 weeks (DOX 4w, N = 33), the experimental regimens MIN 200mg/d for 3 weeks (MIN 3w; N = 30), DOX 200mg/d for 3 weeks plus albendazole (ALB) 800mg/d for 3 days (DOX 3w + ALB 3d, N = 32), DOX 200mg/d for 3 weeks (DOX 3w, N = 31) and ALB 800mg for 3 days (ALB 3d, N = 30). Out of 158 randomized participants, 116 (74.4%) were present for the follow-up at 6 months of whom 99 participants (63.5%) followed the treatment per protocol and underwent surgery. Histological analysis of the adult worms in the extirpated nodules revealed absence of Wolbachia in 98.8% (DOX 4w), 81.4% (DOX 3w + ALB 3d), 72.7% (MIN 3w), 64.1% (DOX 3w) and 35.2% (ALB 3d) of the female worms. All 4 treatment regimens showed superiority to ALB 3d (p < 0.001, p < 0.001, p = 0.002, p = 0.008, respectively), which was confirmed by real-time PCR. Additionally, DOX 4w showed superiority to all other treatment arms. Furthermore DOX 4w and DOX 3w + ALB 3d showed a higher amount of female worms with degenerated embryogenesis compared to ALB 3d (p = 0.028, p = 0.042, respectively). These results confirm earlier studies that DOX 4w is sufficient for Wolbachia depletion and the desired parasitological effects. The data further suggest that there is an additive effect of ALB (3 days) on top of that of DOX alone, and that MIN shows a trend for stronger potency than DOX. These latter two results are preliminary and need confirmation in a fully randomized controlled phase 2 trial. Trial

  4. A Prospective, Multicentre, Open-Label Single-Arm Exploratory Study to Evaluate Efficacy and Safety of Saroglitazar on Hypertriglyceridemia in HIV Associated Lipodystrophy.

    Directory of Open Access Journals (Sweden)

    Alka Deshpande

    Full Text Available This study was designed to explore the efficacy and safety of saroglitazar 4 mg on hypertriglyceridemia in patients with HIV associated lipodystrophy.During this 12-week prospective, multi-centric, open-label, single arm exploratory study, 50 patients were enrolled to receive saroglitazar 4 mg orally once daily in the morning before breakfast. The primary efficacy endpoint was the percent change in triglyceride (TG levels from baseline to Week 6 and Week 12. The secondary efficacy endpoints were assessment of low-density-lipoprotein (LDL, very-low-density-lipoprotein (VLDL, high-density-lipoprotein (HDL, non-HDL cholesterol, total cholesterol, apo-lipoprotein (Apo A1, Apo B, and C-peptide and fasting insulin for HOMA beta and HOMA IR. Safety assessment was performed during the study.Saroglitazar 4 mg significantly decreased the serum TG levels from baseline at Week 6 (percent change: -40.98; 95% CI: -50.82, -31.15 and Week 12 (percent change -45.11; 95% CI: -52.37, -37.86. Reduction in VLDL cholesterol (percent change: -46.33; 95% CI: -52.89, -39.76 and total cholesterol (percent change: 7.37; 95% CI: 1.96, 12.78 was observed at week 12 from baseline. Saroglitazar increased HDL cholesterol (percent change: 34.56, 95% CI: 22.22, 46.90, Apo A1 (percent change: 33.16; 95% CI: 18.69, 47.63 and Apo B (percent change: 10.55, 95% CI: 2.86, 18.25 levels at week 12 from baseline. Saroglitazar treatment led to increase in the C-peptide (percent change: 59.42, 95% CI: 48.78, 70.06, fasting insulin levels (percent change: 47.10; 95% CI: 38.63, 55.57, HOMA of beta cell function for C-peptide (percent change: 71.67; 95% CI: 39.09, 104.26 and HOMA of insulin resistance for C-peptide (percent change: 58.29, 95% CI: 46.74, 69.83 at week 12 from baseline. Saroglitazar treatment was safe and well tolerated in this study.Overall, the observed changes in lipid profile after 12 weeks of saroglitazar treatment were in the direction of improvement in patients with HIV

  5. An Open-Label Study of an Herbal Topical Medication (QoolSkin for Patients with Chronic Plaque Psoriasis

    Directory of Open Access Journals (Sweden)

    Arnon D. Cohen

    2007-01-01

    Full Text Available QoolSkin is novel herbal topical medication indicated for the treatment of patients with psoriasis and we endeavored to determine the efficacy of QoolSkin in patients with chronic plaque psoriasis. In an open-label, parallel-group study conducted at four sites in Israel, patients with chronic plaque psoriasis were treated by application of QoolSkin two to three times per day, for a period of 16 weeks. Clinical assessment was performed using the Psoriasis Area and Severity Index (PASI and the Beer-Sheva Psoriasis Severity Score (BPSS. The study included 100 patients (48 men, 52 women; age 18–65 years. QoolSkin was well tolerated and there were no local or systemic side effects. There was a 19% reduction in PASI, from a mean of 9.8 ± 9.5 before treatment to 8.0 ± 9.6 after treatment (p = 0.09. There was a 20% reduction in BPSS, from a mean of 16.1 ± 9.8 before treatment to 12.8 ± 10.6 after treatment (p = 0.01. The reduction in PASI and BPSS was pronounced in women (32 and 31%, respectively as compared to men (9 and 11%, respectively. The reduction in PASI and BPSS was parallel to the length of time the patients were treated by QoolSkin. In patients treated by one of the investigators, who applied QoolSkin three times per day and for a long period of time (mean 101.1 days, the reduction in PASI was 32.0% and the reduction in BPSS was 37.8%. In patients with chronic plaque psoriasis, QoolSkin treatment was well tolerated. Application of QoolSkin was associated with a decrease in disease severity, as assessed by the patients and physicians. Application of QoolSkin three times per day for long period is associated with a better response to treatment.

  6. Patient-optimized doses of fesoterodine improve bladder symptoms in an open-label, flexible-dose study.

    Science.gov (United States)

    Wyndaele, Jean-Jacques; Goldfischer, Evan R; Morrow, Jon D; Gong, Jason; Tseng, Li-Jung; Choo, Myung-Soo

    2011-02-01

    To assess changes in overactive bladder (OAB) symptoms and patient-reported outcomes in a post hoc analysis in which subjects from a 12-week, open-label, flexible-dose fesoterodine study were stratified according to whether they opted for dose escalation. Subjects with OAB (eight or more micturitions and three or more urgency episodes per 24 h) who reported dissatisfaction with tolterodine within 2 years of screening received fesoterodine 4 mg once daily for 4 weeks, with an optional dose increase to 8 mg after week 4 based on discussion of efficacy and tolerability between the subject and investigator. Subjects completed 5-day diaries, the Patient Perception of Bladder Condition (PPBC) and Urgency Perception Scale (UPS) at baseline and weeks 4 and 12, and the Overactive Bladder Questionnaire (OAB-q) at baseline and week 12. Subjects rated treatment satisfaction at week 12. Dose escalation to 8 mg at week 4 was chosen by 255 (50%) of 513 subjects. At baseline, subjects who opted for dose escalation at week 4 (escalators) had significantly higher means for all diary variables except urgency urinary incontinence (UUI) episodes, significantly greater OAB-q Symptom Bother scores and significantly lower OAB-q health-related quality of life (HRQL) scores (all P fesoterodine significantly improved OAB symptoms and patient-reported outcomes in subjects who chose to remain on the initial 4-mg dose, as well as in the 50% of subjects who escalated to the 8-mg dose after 4 weeks. Non-escalators had significantly fewer OAB symptoms at baseline and significantly greater improvements than escalators before dose escalation. Escalators showed increased symptom relief after dose escalation; improvements in most outcomes were similar among non-escalators and escalators by week 12. Flexible-dose fesoterodine was well tolerated, with similar adverse-event profiles observed in the escalator and non-escalator groups. These results may help clinicians to identify patients more likely to

  7. A multicentre, randomised, open-label, controlled trial evaluating equivalence of inhalational and intravenous anaesthesia during elective craniotomy.

    Science.gov (United States)

    Citerio, Giuseppe; Pesenti, Antonio; Latini, Roberto; Masson, Serge; Barlera, Simona; Gaspari, Flavio; Franzosi, Maria G

    2012-08-01

    A clear preference for intravenous or inhalational anaesthesia has not been established for craniotomy in patients without signs of cerebral hypertension. The NeuroMorfeo trial was designed to test equivalence of inhalational and intravenous anaesthesia maintenance techniques in the postoperative recovery of patients undergoing elective supratentorial surgery. This trial is a multicentre, randomised, open-label, equivalence design. A balanced stratified randomisation scheme was maintained using a centralised randomisation service. Equivalence was tested using the two one-sided tests procedure. Fourteen Italian neuroanaesthesia centres participated in the study from December 2007 to March 2009. Adults, 18 to 75 years old, scheduled for elective supratentorial intracranial surgery under general anaesthesia were eligible for enrolment if they had a normal preoperative level of consciousness and no clinical signs of intracranial hypertension. Patients were randomised to one of three anaesthesia maintenance protocols to determine if sevoflurane-remifentanil or sevoflurane-fentanyl were equivalent to propofol-remifentanil. The primary outcome was the time to achieve an Aldrete postanaesthesia score of at least 9 after tracheal extubation. Secondary endpoints included haemodynamic parameters, quality of the surgical field, perioperative neuroendocrine stress responses and routine postoperative assessments. Four hundred and eleven patients [51% men, mean age 54.8 (SD 13.3) years] were enrolled. Primary outcome data were available for 380. Median (interquartiles) times to reach an Aldrete score of at least 9 were 3.48 (2.02 to 7.56), 3.25 (1.21 to 6.45) and 3.32  min (1.40 to 8.33) for sevoflurane-fentanyl, sevoflurane-remifentanil and propofol-remifentanil anaesthesia respectively, which confirmed equivalence using the two one-sided tests approach. Between-treatment differences in haemodynamic variables were small and not clinically relevant. Urinary catecholamine and

  8. Dexmedetomidine versus midazolam for conscious sedation in endoscopic retrograde cholangiopancreatography: An open-label randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Priyanka Sethi

    2014-01-01

    Full Text Available Background: Traditionally, midazolam has been used for providing conscious sedation in endoscopic retrograde cholangiopancreatography (ERCP. Recently, dexmedetomidine has been tried, but very little evidence exists to support its use. Objective: The primary objective was to compare haemodynamic, respiratory and recovery profile of both drugs. Secondary objective was to compare the degree of comfort experienced by patients and the usefulness of the drug to endoscopist. Study Design: Open-label Randomised Controlled Trial. Methods: Subjects between 18 and 60 years of age with American Society of Anaesthesiologist Grade I-II requiring ERCP were enrolled in two groups (30 each. Both groups received fentanyl 1 μg/kg IV at the beginning of ERCP. Group M received IV midazolam (0.04 mg/kg and additional 0.5 mg doses until Ramsay Sedation Scale (RSS score reached 3-4. Group D received dexmedetomidine at loading dose of 1 μg/kg over 10 min followed by 0.5 μg/kg/h infusion until RSS reached 3-4. The vital parameters (heart rate (HR, blood pressure (BP, respiration rate, SpO 2 , time to achieve RSS 3-4 and facial pain score (FPS were compared during and after the procedure. In the recovery room, time to reach modified Aldrete score (MAS 9-10 and patient and surgeon′s satisfaction scores was also recorded and compared. Any complication during or after the procedure were also noted. Results: In Group D, patients had lower HR and FPS at 5, 10 and 15 min following the initiation of sedation (P<0.05. There was no statistically significant difference in BP and respiratory rate. The procedure elicited a gag response in 29 (97% and 7 (23% subjects in Group M and Group D respectively (P<0.05. MAS of 9-10 at 5 min during recovery was achieved in 27 (90% subjects in Group D in contrast to 5 (17% in Group M (P<0.05. Dexmedetomidine showed higher patient and surgeon satisfaction scores (P<0.05. Conclusion: Dexmedetomidine can be a superior alternative to midazolam

  9. Prolonged-release melatonin for insomnia – an open-label long-term study of efficacy, safety, and withdrawal

    Directory of Open Access Journals (Sweden)

    Lemoine P

    2011-07-01

    Full Text Available Patrick Lemoine1, Doron Garfinkel2, Moshe Laudon3, Tali Nir3, Nava Zisapel3,41The Clinique Lyon-Lumière, Meyzieu, France; 2Geriatric-Palliative Department, Shoham Geriatric Medical Center, Pardes Hanna, Israel; 3Neurim Pharmaceuticals Ltd, Tel-Aviv, Israel; 4Department of Neurobiology Faculty of Life Sciences, Tel Aviv University, Tel Aviv, IsraelBackground: Prolonged-release melatonin (PRM 2 mg is indicated for insomnia in patients aged 55 years and older. A recent double-blind placebo-controlled study demonstrated 6-month efficacy and safety of PRM in insomnia patients aged 18–80 and lack of withdrawal and rebound symptoms upon discontinuation.Objective: To investigate the efficacy, safety, and withdrawal phenomena associated with 6–12 months PRM treatment.Methods: Data from a prospective 6–12-month open-label study of 244 community dwelling adults with primary insomnia, who had participated in a placebo-controlled, double-blind dose-ranging trial of PRM. Patients received PRM nightly, followed by a 2-week withdrawal period. Main outcome measures were patient-reported sleep quality ratings (diary, adverse events, vital signs, and laboratory tests recorded at each visit, and withdrawal symptoms (CHESS-84 [Check-list Evaluation of Somatic Symptoms]. Nocturnal urinary 6-sulfatoxymelatonin excretion, a measure of the endogenous melatonin production, was assessed upon discontinuing long-term PRM.Results: Of the 244 patients, 36 dropped out, 112 completed 6 months of treatment, and the other 96 completed 12 months of treatment. The mean number of nights by which patients reported sleep quality as "good" or "very good" was significantly higher during PRM than before treatment. There was no evidence of tolerance to PRM. Discontinuation of PRM was not associated with rebound insomnia or withdrawal symptoms; on the contrary, residual benefit was observed. PRM was well tolerated, and there was no suppression of endogenous melatonin production

  10. An Open-Label, Randomized Trial of Methylphenidate and Atomoxetine Treatment in Children with Attention-Deficit/Hyperactivity Disorder.

    Science.gov (United States)

    Shang, Chi-Yung; Pan, Yi-Lei; Lin, Hsiang-Yuan; Huang, Lin-Wan; Gau, Susan Shur-Fen

    2015-09-01

    The efficacy of both methylphenidate and atomoxetine has been established in placebo-controlled trials. The present study aimed to directly compare the efficacy of methylphenidate and atomoxetine in improving symptoms among children with attention-deficit/hyperactivity disorder (ADHD). The study sample included 160 drug-naïve children and adolescents 7-16 years of age, with DSM-IV-defined ADHD, randomly assigned to osmotic-release oral system methylphenidate (OROS-methylphenidate) (n=80) and atomoxetine (n=80) in a 24 week, open-label, head-to-head clinical trial. The primary efficacy measure was the score of the ADHD Rating Scale-IV Parents Version: Investigator Administered and Scored (ADHD-RS-IV). The secondary efficacy measures included the Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) and Chinese Swanson, Nolan, and Pelham IV scale (SNAP-IV), based on the ratings of investigators, parents, teachers, and subjects. At week 24, mean changes in ADHD-RS-IV Inattention scores were 13.58 points (Cohen's d, -3.08) for OROS-methylphenidate and 12.65 points (Cohen's d, -3.05) for atomoxetine; and mean changes in ADHD-RS-IV Hyperactivity-Impulsivity scores were 10.16 points (Cohen's d, -1.75) for OROS-methylphenidate and 10.68 points (Cohen's d, -1.87) for atomoxetine. In terms of parent-, teacher-, and self-ratings on behavioral symptoms, both of the two treatment groups significantly decreased on the SNAP-IV scores at the end-point, with effect sizes ranging from 0.9 to 0.96 on the Inattention subscale and from 0.61 to 0.8 on the Hyperactivity/Impulsivity subscale for OROS-methylphenidate; and from 0.51 to 0.88 on the Inattention subscale and from 0.29 to 0.57 on the Hyperactivity/Impulsivity subscale for atomoxetine. No statistically significant differences between treatment groups were observed on the outcome measures. Vomiting, somnolence, and dizziness were reported more often for atomoxetine than for OROS-methylphenidate, whereas insomnia was reported

  11. Pharmacokinetic interaction between udenafil and dapoxetine: a randomized, open-labeled crossover study in healthy male volunteers

    Directory of Open Access Journals (Sweden)

    Kim YH

    2015-02-01

    Full Text Available Yo Han Kim,1 Hee Youn Choi,1 Shi Hyang Lee,1 Hae Sun Jeon,1 Hyeong-Seok Lim,1 Mi Young Bahng,2 Kyun-Seop Bae1 1Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, College of Medicine, University of Ulsan, 2Clinical Development Department, Dong-A ST Co, Ltd, Seoul, Republic of Korea Background: “Udenafil” is a phosphodiesterase-5 inhibitor indicated for erectile dysfunction. “Dapoxetine” is a serotonin transport inhibitor indicated for premature ejaculation. The aim of the study reported here was to investigate the pharmacokinetic drug interaction between udenafil and dapoxetine in healthy male subjects. Methods: An open-label, three-treatment, six-sequence, three-period crossover study was performed in healthy male subjects. In varying sequences, each subjects received single oral doses of udenafil 200 mg, dapoxetine 60 mg, and both treatments. The periods were separated by a washout period of 7 days. Serial blood samples were collected up to 48 hours after dosing. The plasma concentrations of udenafil and dapoxetine were determined using a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were obtained by non-compartmental analysis. Tolerability was assessed throughout the study. Results: Twenty-three healthy subjects completed the study. The geometric mean ratios of the area under the plasma concentration–time curve from time 0 to last measurable time point and measured peak plasma concentration for udenafil were 0.923 (90% confidence interval [CI]: 0.863–0.987 and 0.864 (90% CI: 0.789–0.947, respectively. The geometric mean ratios of the area under the plasma concentration–time curve from time 0 to last measurable time point and measured peak plasma concentration for dapoxetine were 1.125 (90% CI: 1.044–1.213 and 0.837 (90% CI: 0.758–0.925, respectively. There were no serious adverse events reported, and none of the subjects dropped out due to adverse events

  12. Holter-electrocardiogram-monitoring in patients with acute ischaemic stroke (Find-AFRANDOMISED): an open-label randomised controlled trial.

    Science.gov (United States)

    Wachter, Rolf; Gröschel, Klaus; Gelbrich, Götz; Hamann, Gerhard F; Kermer, Pawel; Liman, Jan; Seegers, Joachim; Wasser, Katrin; Schulte, Anna; Jürries, Falko; Messerschmid, Anna; Behnke, Nico; Gröschel, Sonja; Uphaus, Timo; Grings, Anne; Ibis, Tugba; Klimpe, Sven; Wagner-Heck, Michaela; Arnold, Magdalena; Protsenko, Evgeny; Heuschmann, Peter U; Conen, David; Weber-Krüger, Mark

    2017-04-01

    Atrial fibrillation is a major risk factor for recurrent ischaemic stroke, but often remains undiagnosed in patients who have had an acute ischaemic stroke. Enhanced and prolonged Holter-electrocardiogram-monitoring might increase detection of atrial fibrillation. We therefore investigated whether enhanced and prolonged rhythm monitoring was better for detection of atrial fibrillation than standard care procedures in patients with acute ischaemic stroke. Find-AFrandomised is an open-label randomised study done at four centres in Germany. We recruited patients with acute ischaemic stroke (symptoms for 7 days or less) aged 60 years or older presenting with sinus rhythm and without history of atrial fibrillation. Patients were included irrespective of the suspected cause of stroke, unless they had a severe ipsilateral carotid or intracranial artery stenosis, which were the exclusion criteria. We used a computer-generated allocation sequence to randomly assign patients in a 1:1 ratio with permuted block sizes of 2, 4, 6, and 8, stratified by centre, to enhanced and prolonged monitoring (ie, 10-day Holter-electrocardiogram [ECG]-monitoring at baseline, and at 3 months and 6 months of follow-up) or standard care procedures (ie, at least 24 h of rhythm monitoring). Participants and study physicians were not masked to group assignment, but the expert committees that adjudicated endpoints were. The primary endpoint was the occurrence of atrial fibrillation or atrial flutter (30 sec or longer) within 6 months after randomisation and before stroke recurrence. Because Holter ECG is a widely used procedure and not known to harm patients, we chose not to assess safety in detail. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01855035. Between May 8, 2013, and Aug 31, 2014, we recruited 398 patients. 200 patients were randomly assigned to the enhanced and prolonged monitoring group and 198 to the standard care group. After 6 months

  13. Oral versus intramuscular cobalamin treatment in megaloblastic anemia: a single-center, prospective, randomized, open-label study.

    Science.gov (United States)

    Bolaman, Zahit; Kadikoylu, Gurhan; Yukselen, Vahit; Yavasoglu, Irfan; Barutca, Sabri; Senturk, Taskin

    2003-12-01

    Cobalamin (vitamin B12) deficiency, the most common cause of megaloblastic anemia, is treated with intramuscular (IM) cobalamin. It has been suggested by some investigators that oral (p.o.) cobalamin treatment may be as effective in the treatment of this condition, with the advantages of ease of administration and lower cost. This study assessed the effects and cost of p.o. versus i.m. cobalamin treatment in patients with megaloblastic anemia due to cobalamin deficiency. This was a 90-day, prospective, randomized, open-label study conducted at the Division of Hematology, Department of Internal Medicine, Adnan Menderes University Research and Practice Hospital (Aydin, Turkey). Patients aged > or =16 years with megaloblastic anemia due to cobalamin deficiency were randomized to receive 1000-microg cobalamin p.o. once daily for 10 days (p.o. group) or 1000-microg cobalamin i.m. once daily for 10 days (i.m. group). After 10 days, both treatments were administered once a week for 4 weeks, and after that, once a month for life. Patients were assessed for the presence of reticulocytosis between treatment days 5 and 10 until it was detected. Therapeutic effectiveness was assessed by measuring hematologic parameters on days 0, 10, 30, and 90 and serum vitamin B12 concentration on days 0 and 90. The Mini-Mental State Examination was used before and after the B12 therapy for cognitive function assessment and 125-Hz diapozone was used for vibration threshold testing. Neurologic sensory assessment, including soft-touch and pinprick examinations, was used to identify neuropathy at baseline and study end. Tolerability was assessed using laboratory tests and patient interview. Cost was assessed using the cost of the study drug and of the injection. Sixty patients completed the study 26 in the p.o. group (16 men, 10 women; mean [SD] age, 60 [15] years) and 34 in the i.m. group (17 men, 17 women; mean [SD] age, 64 [10] years). Reticulocytosis was observed in all patients. In the p

  14. Prospective, open-label study to validate proper use of the Versacloz™ (clozapine oral suspension kit by people with schizophrenia

    Directory of Open Access Journals (Sweden)

    Andre AD

    2015-05-01

    Full Text Available Anthony D Andre Interface Analysis Associates, Saratoga, CA, USA Purpose: This study was designed to validate that people with schizophrenia can correctly, safely, and effectively prepare doses of Versacloz™ using the Versacloz oral suspension kit and instructions for use (IFU.Materials and methods: This was a prospective, open-label, simulated-use validation study of 61 people with schizophrenia who were stabilized on clozapine or were clozapine-naive and stabilized on another antipsychotic treatment. Participants were randomized to one of two groups: untrained (n=46 and trained (n=15. Participants were asked to select the proper syringe and prepare two test doses of 1, 3.5, or 5 mL, as randomly assigned. Participants in the untrained group did not receive any training on using the kit, but had access to kit materials, including packaging and the IFU; both test dose preparations were unaided. Participants in the trained group received brief training from the moderator, and then prepared one test dose during training and one unaided test dose during the study period. Prepared placebo doses were not ingested. Performance and behavior were assessed in 14 critical tasks identified in the user failure mode and effects analysis. Test dose failures or dose errors (threshold ±0.1 mL were assessed. Subjective participant assessments of usability were captured in interviews and IFU comprehension was probed.Results: A total of 107 test doses were prepared: 92 and 15 by the untrained and trained groups, respectively. Overall success for unassisted dose preparation was 87.9%; all test failures (failure to shake the bottle or failure to obtain the correct test dose occurred in the untrained group. All participants selected the correct syringe for their assigned dose.Conclusion: This study shows that the Versacloz oral suspension kit and IFU can be correctly, safely, and effectively used to prepare doses by people with schizophrenia, with few instances of

  15. A multicenter phase II study of TAS-102 monotherapy in patients with pre-treated advanced gastric cancer (EPOC1201).

    Science.gov (United States)

    Bando, Hideaki; Doi, Toshihiko; Muro, Kei; Yasui, Hirofumi; Nishina, Tomohiro; Yamaguchi, Kensei; Takahashi, Shunji; Nomura, Shogo; Kuno, Hirofumi; Shitara, Kohei; Sato, Akihiro; Ohtsu, Atsushi

    2016-07-01

    American phase I studies have reported that the recommended dose of TAS-102 (trifluridine/tipiracil) was 25 mg/m(2) twice a day (b.i.d.), although this schedule did not provide clinically relevant improvements in a phase II study of advanced gastric cancer (AGC). However, a pivotal phase III study revealed that TAS-102 at 35 mg/m(2) b.i.d. provided a clinically relevant improvement in overall survival (OS) among patients with metastatic colorectal cancer. Therefore, we re-evaluated the efficacy, safety, and pharmacokinetic parameters of TAS-102 at 35 mg/m(2) b.i.d among Japanese patients with AGC. All patients had undergone one or two previous chemotherapy regimens that contained fluoropyrimidine, platinum agents, and taxanes or irinotecan. The primary end-point target was a disease control rate (DCR) of ≥50% after 8 weeks of the 35 mg/m(2) b.i.d. schedule. Twenty-nine patients were assessable after completing the 35 mg/m(2) b.i.d. schedule. The investigator-determined DCR was 65.5% (95% confidence interval [CI], 45.7-82.1%) and the independent central review's DCR was 51.9% (95% CI, 31.9-71.3%); both results exceeded the primary end-point target. The median progression-free survival and OS were 2.9 months (95% CI, 1.1-5.3 months) and 8.7 months (95% CI, 5.7-14.9 months), respectively. The grade III/IV adverse events included neutropenia (69.0%), leucopaenia (41.4%), anaemia (20.7%), and anorexia (10.3%). No AGC-specific toxicities were detected. The 35 mg/m(2) b.i.d. dose of TAS-102 provided positive efficacy and an acceptable toxicity profile in patients with AGC. A randomised, double-blind, placebo-controlled, phase III study is ongoing to validate these findings. UMIN000007421. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  16. Immunogenicity and safety of a cell culture-based quadrivalent influenza vaccine in adults: A Phase III, double-blind, multicenter, randomized, non-inferiority study

    Science.gov (United States)

    Bart, Stephan; Cannon, Kevin; Herrington, Darrell; Mills, Richard; Forleo-Neto, Eduardo; Lindert, Kelly; Abdul Mateen, Ahmed

    2016-01-01

    ABSTRACT Quadrivalent influenza vaccines (QIVs), which include both B lineage strains, are expected to provide broader protection than trivalent influenza vaccines (TIVs). The non-inferiority, immunogenicity, and safety of a cell culture-based investigational QIVc and 2 TIVs (TIV1c, TIV2c), in adults (≥18 y), were evaluated in this Phase III, double-blind, multicenter study. A total of 2680 age-stratified subjects were randomized (2:1:1) to receive 1 dose of QIVc (n = 1335), TIV1c (n = 676), or TIV2c (n = 669). TIV1c (B/Yamagata) and TIV2c (B/Victoria) differed only in B strain lineage. The primary objective was to demonstrate non-inferiority of the hemagglutinin-inhibition antibody responses of QIVc against TIVc, 22 d post-vaccination. Secondary objectives included the evaluation of immunogenicity of QIVc and TIVc in younger (≥18 – <65 y) and older (≥65 y) adults. Hemagglutinin inhibition assays were performed at days 1 and 22. Solicited local and systemic adverse events (AEs) were monitored for 7 d post-vaccination, and unsolicited AEs and serious AEs until day 181. QIVc met the non-inferiority criteria for all 4 vaccine strains and demonstrated superiority for both influenza B strains over the unmatched B strain included in the TIV1c and TIV2c, when geometric mean titers and seroconversion rates with TIVc were compared at day 22. Between 48%–52% of subjects experienced ≥1 solicited AE, the most common being injection-site pain and headache. Serious AEs were reported by ≤1% of subjects, none were vaccine-related. The results indicate that QIVc is immunogenic and well tolerated in both younger and older adults. The immunogenicity and safety profiles of QIVc and TIVc were comparable at all ages evaluated. PMID:27322354

  17. Results of a Multicenter Phase II Trial of Brentuximab Vedotin as Second-Line Therapy before Autologous Transplantation in Relapsed/Refractory Hodgkin Lymphoma.

    Science.gov (United States)

    Chen, Robert; Palmer, Joycelynne M; Martin, Peter; Tsai, Nicole; Kim, Young; Chen, Bihong T; Popplewell, Leslie; Siddiqi, Tanya; Thomas, Sandra H; Mott, Michelle; Sahebi, Firoozeh; Armenian, Saro; Leonard, John; Nademanee, Auayporn; Forman, Stephen J

    2015-12-01

    This multicenter prospective phase II study examines the activity and tolerability of brentuximab vedotin as second-line therapy in patients with Hodgkin lymphoma that was relapsed or refractory after induction therapy. Brentuximab vedotin (1.8 mg/kg) was administered i.v. on day 1 of a 21-day cycle for a total of 4 cycles. Patients then proceeded to autologous hematopoietic cell transplantation (AHCT), if eligible, with or without additional salvage therapy, based on remission status after brentuximab vedotin. The primary endpoint was overall response rate (ORR). Secondary endpoints were safety, stem cell mobilization/collection, AHCT outcomes, and association of CD68(+) with outcomes. Of 37 patients, the ORR was 68% (13 complete remission, 12 partial remission). The regimen was well tolerated with few grade 3/4 adverse events, including lymphopenia (1), neutropenia (3), rash (2), and hyperuricemia (1). Thirty-two patients (86%) were able to proceed to AHCT, with 24 patients (65%) in complete remission at time of AHCT. Thirteen patients in complete remission, 4 in partial remission, and 1 with stable disease (49%) received AHCT without salvage combination chemotherapy. CD68 expression did not correlate with response to brentuximab vedotin. The median number of stem cells mobilized was 6.0 × 10(6) (range, 2.6 to 34), and median number of days to obtain minimum collection (2 × 10(6)) was 2 (range, 1 to 6). Brentuximab vedotin as second-line therapy is active, well tolerated, and allows adequate stem cell collection and engraftment. For Hodgkin lymphoma patients with relapsed/refractory disease after induction therapy, second-line brentuximab vedotin, followed by combination chemotherapy for residual disease, can effectively bridge patients to AHCT.

  18. Preoperative Chemotherapy in Patients With Intermediate-Risk Rectal Adenocarcinoma Selected by High-Resolution Magnetic Resonance Imaging: The GEMCAD 0801 Phase II Multicenter Trial

    Science.gov (United States)

    Brown, Gina; Estevan, Rafael; Salud, Antonieta; Montagut, Clara; Maurel, Joan; Safont, Maria Jose; Aparicio, Jorge; Feliu, Jaime; Vera, Ruth; Alonso, Vicente; Gallego, Javier; Martin, Marta; Pera, Miguel; Sierra, Enrique; Serra, Javier; Delgado, Salvadora; Roig, Jose V.; Santos, Jesus; Pericay, Carles

    2014-01-01

    Background. The need for preoperative chemoradiation or short-course radiation in all T3 rectal tumors is a controversial issue. A multicenter phase II trial was undertaken to evaluate the efficacy and safety of neoadjuvant capecitabine and oxaliplatin combined with bevacizumab in patients with intermediate-risk rectal adenocarcinoma. Methods. We recruited 46 patients with T3 rectal adenocarcinoma selected by magnetic resonance imaging (MRI) who were candidates for (R0) resection located in the middle third with clear mesorectal fascia and who were selected by pelvic MRI. Patients received four cycles of neoadjuvant capecitabine and oxaliplatin combined with bevacizumab (final cycle without bevacizumab) before total mesorectal excision (TME). In case of progression, preoperative chemoradiation was planned. The primary endpoint was overall response rate (ORR). Results. On an intent-to-treat analysis, the ORR was 78% (n = 36; 95% confidence interval [CI]: 63%–89%) and no progression was detected. Pathologic complete response was observed in nine patients (20%; 95% CI: 9–33), and T downstaging was observed in 48%. Forty-four patients proceeded to TME, and all had R0 resection. During preoperative therapy, two deaths occurred as a result of pulmonary embolism and diarrhea, respectively, and one patient died after surgery as a result of peritonitis secondary to an anastomotic leak (AL). A 13% rate of AL was higher than expected. The 24-month disease-free survival rate was 75% (95% CI: 60%–85%), and the 2-year local relapse rate was 2% (95% CI: 0%–11%). Conclusion. In this selected population, initial chemotherapy results in promising activity, but the observed toxicity does not support further investigation of this specific regimen. Nevertheless, these early results warrant further testing of this strategy in an enriched population and in randomized trials. PMID:25209376

  19. A randomized, double blind, placebo-controlled, multicenter phase II trial of Allisartan Isoproxil in essential hypertensive population at low-medium risk.

    Science.gov (United States)

    Li, Ying; Li, Xiao-hui; Huang, Zhi-jun; Yang, Guo-ping; Zhang, Guo-gang; Zhao, Shui-ping; Guo, Ying; Lu, Shi-juan; Ma, Jian-lin; Meng, Fan-bo; Chen, Ping; Yuan, Hong

    2015-01-01

    Angiotensin II receptor blockers (ARBs) is a well-tolerated class of antihypertensive agents, exhibiting effective antihypertensive and cardiovascular protective function. The objective of the study was to examine the efficacy and safety of Allisartan Isoproxil, a newly developed, selective, nonpeptide blocker of the angiotensin II type 1 receptor (AT1R), in essential hypertensive patients at low-medium risk. A Phase II prospective, randomized, double-blind, placebo-controlled, multicenter trial comparing Allisartan Isoproxil 240mg versus placebo was conducted in essential hypertensive patients at low-medium risk at 8 sites in China. After a 2-week placebo baseline period, 275 patients received once-daily treatment with Allisartan Isoproxil 240mg or placebo randomly for 8 weeks. Systolic/diastolic blood pressure (SBP/DBP) was measured at week 2, 4 and 8. By the end of treatment, mean reductions from baseline of SBP and DBP in Allisartan Isoproxil and placebo groups were 14.5/10.4 and 8.3/7.7 mmHg, respectively (Psafety and tolerability, there were no report of death and serious adverse event (SAE) in all subjects. There was no difference of frequency between two groups in adverse event (AE) and adverse drug reaction (ADR) (P>0.05). No one withdraw because of an ADR in two groups. 124 patients received additional 56 weeks treatment with Allisartan Isoproxil and 84 of them completed the study. The rate of effective BP control kept up to 80% since week 24. No significant clinical change was observed and ADRs were generally mild or moderate during the long-term study. Allisartan Isoproxil 240mg was effective and safe for essential hypertension patients at low-medium risk. http://www.chictr.org/cn/ ChiCTR-TRC-10000886.

  20. Preoperative chemotherapy in patients with intermediate-risk rectal adenocarcinoma selected by high-resolution magnetic resonance imaging: the GEMCAD 0801 Phase II Multicenter Trial.

    Science.gov (United States)

    Fernandez-Martos, Carlos; Brown, Gina; Estevan, Rafael; Salud, Antonieta; Montagut, Clara; Maurel, Joan; Safont, Maria Jose; Aparicio, Jorge; Feliu, Jaime; Vera, Ruth; Alonso, Vicente; Gallego, Javier; Martin, Marta; Pera, Miguel; Sierra, Enrique; Serra, Javier; Delgado, Salvadora; Roig, Jose V; Santos, Jesus; Pericay, Carles

    2014-10-01

    The need for preoperative chemoradiation or short-course radiation in all T3 rectal tumors is a controversial issue. A multicenter phase II trial was undertaken to evaluate the efficacy and safety of neoadjuvant capecitabine and oxaliplatin combined with bevacizumab in patients with intermediate-risk rectal adenocarcinoma. We recruited 46 patients with T3 rectal adenocarcinoma selected by magnetic resonance imaging (MRI) who were candidates for (R0) resection located in the middle third with clear mesorectal fascia and who were selected by pelvic MRI. Patients received four cycles of neoadjuvant capecitabine and oxaliplatin combined with bevacizumab (final cycle without bevacizumab) before total mesorectal excision (TME). In case of progression, preoperative chemoradiation was planned. The primary endpoint was overall response rate (ORR). On an intent-to-treat analysis, the ORR was 78% (n = 36; 95% confidence interval [CI]: 63%-89%) and no progression was detected. Pathologic complete response was observed in nine patients (20%; 95% CI: 9-33), and T downstaging was observed in 48%. Forty-four patients proceeded to TME, and all had R0 resection. During preoperative therapy, two deaths occurred as a result of pulmonary embolism and diarrhea, respectively, and one patient died after surgery as a result of peritonitis secondary to an anastomotic leak (AL). A 13% rate of AL was higher than expected. The 24-month disease-free survival rate was 75% (95% CI: 60%-85%), and the 2-year local relapse rate was 2% (95% CI: 0%-11%). In this selected population, initial chemotherapy results in promising activity, but the observed toxicity does not support further investigation of this specific regimen. Nevertheless, these early results warrant further testing of this strategy in an enriched population and in randomized trials. ©AlphaMed Press; the data published online to support this summary is the property of the authors.

  1. A randomized, double blind, placebo-controlled, multicenter phase II trial of Allisartan Isoproxil in essential hypertensive population at low-medium risk.

    Directory of Open Access Journals (Sweden)

    Ying Li

    Full Text Available Angiotensin II receptor blockers (ARBs is a well-tolerated class of antihypertensive agents, exhibiting effective antihypertensive and cardiovascular protective function. The objective of the study was to examine the efficacy and safety of Allisartan Isoproxil, a newly developed, selective, nonpeptide blocker of the angiotensin II type 1 receptor (AT1R, in essential hypertensive patients at low-medium risk.A Phase II prospective, randomized, double-blind, placebo-controlled, multicenter trial comparing Allisartan Isoproxil 240mg versus placebo was conducted in essential hypertensive patients at low-medium risk at 8 sites in China. After a 2-week placebo baseline period, 275 patients received once-daily treatment with Allisartan Isoproxil 240mg or placebo randomly for 8 weeks. Systolic/diastolic blood pressure (SBP/DBP was measured at week 2, 4 and 8. By the end of treatment, mean reductions from baseline of SBP and DBP in Allisartan Isoproxil and placebo groups were 14.5/10.4 and 8.3/7.7 mmHg, respectively (P0.05. No one withdraw because of an ADR in two groups. 124 patients received additional 56 weeks treatment with Allisartan Isoproxil and 84 of them completed the study. The rate of effective BP control kept up to 80% since week 24. No significant clinical change was observed and ADRs were generally mild or moderate during the long-term study.Allisartan Isoproxil 240mg was effective and safe for essential hypertension patients at low-medium risk.http://www.chictr.org/cn/ ChiCTR-TRC-10000886.

  2. First line chemotherapy with planned sequential administration of gemcitabine followed by docetaxel in elderly advanced non-small-cell lung cancer patients: a multicenter phase II study

    Science.gov (United States)

    Tibaldi, C; Vasile, E; Antonuzzo, A; Di Marsico, R; Fabbri, A; Innocenti, F; Tartarelli, G; Amoroso, D; Andreuccetti, M; Dico, M Lo; Falcone, A

    2008-01-01

    This multicenter phase II study evaluated, in chemonaive patients with stage IIIB–IV NSCLC, age ⩾70 and with a performance status 0–2, the activity, efficacy and tolerability of planned sequential administration of gemcitabine 1200 mg m−2 on days 1 and 8 every 3 weeks for three courses followed by three cycles of docetaxel 37.5 mg m−2 on days 1 and 8 every 3 weeks, provided there was no evidence of disease progression. A total of 56 patients entered the study. According to intention-to-treat analysis, the objective response rate was 16.0% (95% CI 7.6–28.3%); 23 patients (41.0%) had stable disease and 24 patients (43%) had progressive disease. Five patients who had a stable disease after three courses of gemcitabine obtained a conversion to partial response by docetaxel. Median time to progression was 4.8 months (95% CI 3.6–6.0 months) and median duration of survival was 8.0 months (95% CI 5.6–10.5 months). The 1-year survival rate was 34%. No grade 4 haematological toxicity was observed and grade 3 neutropenia and thrombocytopenia were reported in 5.4 and 3.6% of the patients, respectively. Grade 3/4 mucositis and grade 3 diarrhoea, both occurred in 3.6% of the patients and grade 3 asthenia was observed in 9% of patients. One patient reported a grade 4 skin toxicity. No treatment-related deaths occurred. Sequential gemcitabine and docetaxel is a well-tolerated and effective regimen in elderly advanced NSCLC patients. PMID:18212755

  3. Adjuvant gemcitabine versus NEOadjuvant gemcitabine/oxaliplatin plus adjuvant gemcitabine in resectable pancreatic cancer: a randomized multicenter phase III study (NEOPAC study

    Directory of Open Access Journals (Sweden)

    Moehler Markus

    2011-08-01

    Full Text Available Abstract Background Despite major improvements in the perioperative outcome of pancreas surgery, the prognosis of pancreatic cancer after curative resection remains poor. Adjuvant chemotherapy increases disease-free and overall survival, but this treatment cannot be offered to a significant proportion of patients due to the surgical morbidity. In contrast, almost all patients can receive (neoadjuvant chemotherapy before surgery. This treatment is safe and effective, and has resulted in a median survival of 26.5 months in a recent phase II trial. Moreover, neoadjuvant chemotherapy improves the nutritional status of patients with pancreatic cancer. This multicenter phase III trial (NEOPAC has been designed to explore the efficacy of neoadjuvant chemotherapy. Methods/Design This is a prospective randomized phase III trial. Patients with resectable cytologically proven adenocarcinoma of the pancreatic head are eligible for this study. All patients must be at least 18 years old and must provide written informed consent. An infiltration of the superior mesenteric vein > 180° or major visceral arteries are considered exclusion criteria. Eligible patients will be randomized to surgery followed by adjuvant gemcitabine (1000 mg/m2 for 6 months or neoadju