WorldWideScience

Sample records for 24-week open-label phase

  1. Improvement in social and cognitive functioning associated with paliperidone extended-release treatment in patients with schizophrenia: a 24-week, single arm, open-label study

    Science.gov (United States)

    Shi, Chuan; Yao, Shu Qiao; Xu, Yi Feng; Shi, Jian Guo; Xu, Xiu Feng; Zhang, Cong Pei; Jin, Hua; Yu, Xin

    2016-01-01

    Purpose This single-arm, open-label study aimed to explore the effects of extended-release paliperidone on social and cognitive function in patients with schizophrenia. Methods Paliperidone extended-release (flexible dose ranging from 3 to 12 mg/day orally) was administered for 24 weeks in patients with schizophrenia. Patient function was assessed using the personal and social performance scale, measurement and treatment research to improve cognition in schizophrenia initiative-consensus cognitive battery, positive and negative syndrome scale, and clinical global impression-severity. Results Ninety patients were included in the full analysis set, while 72 patients were included in the per protocol set. The personal and social performance score was 54.3±14.3 at baseline, and significantly increased to 73.4±12.6 at week 24 (Pschizophrenia initiative-consensus cognitive battery assessment, six of the nine individual subtests, six of the seven cognitive domains, and total cognitive scores improved significantly (Pschizophrenia.

  2. Milnacipran treatment and potential biomarkers in depressed patients following an initial SSRI treatment failure: a prospective, open-label, 24-week study

    Directory of Open Access Journals (Sweden)

    Hashimoto T

    2015-12-01

    Full Text Available Tasuku Hashimoto,1,2 Daiji Sakurai,1 Yasunori Oda,1 Tadashi Hasegawa,3 Nobuhisa Kanahara,4 Tsuyoshi Sasaki,3 Hideki Komatsu,3,5 Junpei Takahashi,1,5 Takahiro Oiwa,6 Yoshimoto Sekine,4,5 Hiroyuki Watanabe,1 Masaomi Iyo1,3 1Department of Psychiatry, Chiba University Graduate School of Medicine, 2Sodegaura Satsukidai Hospital, 3Department of Psychiatry, Chiba University Hospital, 4Division of Medical Treatment and Rehabilitation, Centre for Forensic Mental Health, Chiba University, 5Choshi Kokoro Clinic, 6Mobara Shinkeika Hospital, Chiba, Japan Background: We assessed the effect of switching patients with major depressive disorder to milnacipran following an initial selective serotonin reuptake inhibitor treatment failure, and explored potential biomarkers in their blood.Methods: We conducted a prospective, open-label, 24-week trial. Depression was assessed with the 17-item Hamilton Depression Rating Scale. Patients showing a ≥50% reduction in Hamilton Depression Rating Scale scores from baseline to final visit were considered responders. Regarding adverse effects (AEs, moderate-to-severe AEs were specifically identified as effects that required any medical treatment or that induced treatment withdrawals. We also measured blood levels of various molecules including inflammatory cytokines.Results: Of the 30 participants who enrolled, 17 completed this study. The responder rate was 30% (n=10. Baseline serum levels of interleukin-6 (Z=-2.155; P=0.031 and interleukin-8 (Z=-2.616; P=0.009 were significantly higher when moderate-to-severe AEs were present (n=13 patients with moderate-to-severe AEs. Serum levels of macrophage inflammatory protein-1β showed a significant continuous decrease from the baseline level (Friedman’s test: χ2=23.9, df=4, P<0.001 only in non-responders.Conclusion: These results demonstrate that serum levels of interleukin-6, interleukin-8, and macrophage inflammatory protein-1β as potential blood biomarkers could be utilized

  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. Morning and evening behavior in children and adolescents treated with atomoxetine once daily for Attention-Deficit/Hyperactivity Disorder (ADHD: Findings from two 24-week, open-label studies

    Directory of Open Access Journals (Sweden)

    Schacht Alexander

    2009-02-01

    Full Text Available Abstract Background The impact of once daily atomoxetine treatment on symptoms in children and adolescents with ADHD may vary over the day. In order to capture such variations, two studies were undertaken in children and adolescents with ADHD using two instruments that capture morning and evening behavior and ADHD-related difficulties over the day. This secondary measure analysis builds on two primary analyses that were conducted separately for children and adolescents and also published separately. Methods In two open-label studies, ADHD patients aged 6–17 years (n = 421, received atomoxetine in the morning (target-dose 0.5–1.2 mg/kg/day for up to 24 weeks. Morning and evening behavior was assessed using the investigator-rated Weekly Rating of Evening and Morning Behavior (WREMB-R scale. ADHD-related difficulties at various times of the day (morning, during school, during homework, evening were assessed using the Global Impression of Perceived Difficulties (GIPD scale, rated by patients, parents and physicians. Data from both studies were combined for this secondary measure analysis. Results Both WREMB-R subscores decreased significantly over time, the evening subscore from 13.7 (95% CI 13.2;14.2 at baseline to 8.0 (7.4;8.5 at week 2, the morning subscore from 4.3 (4.0;4.5 to 2.4 (2.2;2.6. Scores then remained stable until week 24. All GIPD items improved correspondingly. At all times of the day, patients rated ADHD-related difficulties as less severe than parents and physicians. Conclusion These findings from two open-label studies suggest that morning and evening behavior and ADHD-related difficulties in the mornings and evenings improve over time with once daily atomoxetine treatment.

  5. Efficacy and safety of abatacept for patients with Sjögren's syndrome associated with rheumatoid arthritis: rheumatoid arthritis with orencia trial toward Sjögren's syndrome Endocrinopathy (ROSE) trial-an open-label, one-year, prospective study-Interim analysis of 32 patients for 24 weeks.

    Science.gov (United States)

    Tsuboi, Hiroto; Matsumoto, Isao; Hagiwara, Shinya; Hirota, Tomoya; Takahashi, Hiroyuki; Ebe, Hiroshi; Yokosawa, Masahiro; Hagiya, Chihiro; Asashima, Hiromitsu; Takai, Chinatsu; Miki, Haruka; Umeda, Naoto; Kondo, Yuya; Ogishima, Hiroshi; Suzuki, Takeshi; Hirata, Shintaro; Saito, Kazuyoshi; Tanaka, Yoshiya; Horai, Yoshiro; Nakamura, Hideki; Kawakami, Atsushi; Sumida, Takayuki

    2015-03-01

    Abstract Objective. To assess the efficacy and safety of abatacept for secondary Sjögren's syndrome (SS) associated with rheumatoid arthritis (RA). Methods. The primary endpoint of this 1-year, open-labeled, prospective, observational multicenter study of RA-associated secondary SS was the rate of SDAI remission at 52 weeks after initiation of abatacept therapy. The secondary endpoints included that of Saxson's test and Schirmer's test. Adverse events during the study period were also analyzed. Results. Thirty-two patients (all females) were enrolled in this study. Interim analysis at 24 weeks included assessment of efficacy (n = 31) and safety (n = 32). The mean SDAI decreased from 19.8 ± 11.0 (± SD) at baseline to 9.9 ± 9.9 at 24 weeks (P < 0.05). Patients with clinical remission, as assessed by SDAI, increased from 0 patient (0 week) to 8 patients (25.8%) at 24 weeks. Saliva volume (assessed by Saxson's test) increased slightly from 2232 ± 1908 (0 week) to 2424 ± 2004 (24 weeks) mg/2 min (n = 29). In 11 patients with Greenspan grading 1/2 of labial salivary glands biopsy, saliva volume increased from 2945 ± 2090 (0 week) to 3419 ± 2121 (24 weeks) mg/2 min (P < 0.05). Schirmer's test for tear volume showed increase from 3.6 ± 4.6 (0 week) to 5.5 ± 7.1 (24 weeks) mm/5 min (n = 25; P < 0.05). Five adverse events occurred in five of 32 patients (15.6%), and three of these events were infections. Conclusion. Abatacept seems to be effective for both RA and RA-related secondary SS.

  6. Efficacy and safety of abatacept for patients with Sjögren's syndrome associated with rheumatoid arthritis: Rheumatoid Arthritis with Orencia Trial toward Sjögren's syndrome Endocrinopathy (ROSE) trial—an open-label, one-year, prospective study—Interim analysis of 32 patients for 24 weeks

    Science.gov (United States)

    Tsuboi, Hiroto; Matsumoto, Isao; Hagiwara, Shinya; Hirota, Tomoya; Takahashi, Hiroyuki; Ebe, Hiroshi; Yokosawa, Masahiro; Hagiya, Chihiro; Asashima, Hiromitsu; Takai, Chinatsu; Miki, Haruka; Umeda, Naoto; Kondo, Yuya; Ogishima, Hiroshi; Suzuki, Takeshi; Hirata, Shintaro; Saito, Kazuyoshi; Tanaka, Yoshiya; Horai, Yoshiro; Nakamura, Hideki; Kawakami, Atsushi

    2015-01-01

    Objective To assess the efficacy and safety of abatacept for secondary Sjögren's syndrome (SS) associated with rheumatoid arthritis (RA). Methods The primary endpoint of this 1-year, open-labeled, prospective, observational multicenter study of RA-associated secondary SS was the rate of SDAI remission at 52 weeks after initiation of abatacept therapy. The secondary endpoints included that of Saxson's test and Schirmer's test. Adverse events during the study period were also analyzed. Results Thirty-two patients (all females) were enrolled in this study. Interim analysis at 24 weeks included assessment of efficacy (n = 31) and safety (n = 32). The mean SDAI decreased from 19.8 ± 11.0 (± SD) at baseline to 9.9 ± 9.9 at 24 weeks (P < 0.05). Patients with clinical remission, as assessed by SDAI, increased from 0 patient (0 week) to 8 patients (25.8%) at 24 weeks. Saliva volume (assessed by Saxson's test) increased slightly from 2232 ± 1908 (0 week) to 2424 ± 2004 (24 weeks) mg/2 min (n = 29). In 11 patients with Greenspan grading 1/2 of labial salivary glands biopsy, saliva volume increased from 2945 ± 2090 (0 week) to 3419 ± 2121 (24 weeks) mg/2 min (P < 0.05). Schirmer's test for tear volume showed increase from 3.6 ± 4.6 (0 week) to 5.5 ± 7.1 (24 weeks) mm/5 min (n = 25; P < 0.05). Five adverse events occurred in five of 32 patients (15.6%), and three of these events were infections. Conclusion Abatacept seems to be effective for both RA and RA-related secondary SS. PMID:25211401

  7. 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). PMID:26050104

  8. Dolutegravir in Antiretroviral-Experienced Patients With Raltegravir- and/or Elvitegravir-Resistant HIV-1: 24-Week Results of the Phase III VIKING-3 Study

    Science.gov (United States)

    Castagna, Antonella; Maggiolo, Franco; Penco, Giovanni; Wright, David; Mills, Anthony; Grossberg, Robert; Molina, Jean-Michel; Chas, Julie; Durant, Jacques; Moreno, Santiago; Doroana, Manuela; Ait-Khaled, Mounir; Huang, Jenny; Min, Sherene; Song, Ivy; Vavro, Cindy; Nichols, Garrett; Yeo, Jane M.; Aberg, J.; Akil, B.; Arribas, J. R.; Baril, J.-G.; Blanco Arévalo, J. L.; Blanco Quintana, F.; Blick, G.; Boix Martínez, V.; Bouchaud, O.; Branco, T.; Bredeek, U. F.; Castro Iglesias, M.; Clumeck, N.; Conway, B.; DeJesus, E.; Delassus, J.-L.; De Truchis, P.; Di Perri, G.; Di Pietro, M.; Duggan, J.; Duvivier, C.; Elion, R.; Eron, J.; Fish, D.; Gathe, J.; Haubrich, R.; Henderson, H.; Hicks, C.; Hocqueloux, L.; Hodder, S.; Hsiao, C.-B.; Katlama, C.; Kozal, M.; Kumar, P.; Lalla-Reddy, S.; Lazzarin, A.; Leoncini, F.; Llibre, J. M.; Mansinho, K.; Morlat, P.; Mounzer, K.; Murphy, M.; Newman, C.; Nguyen, T.; Nseir, B.; Philibert, P.; Pialoux, G.; Poizot-Martin, I.; Ramgopal, M.; Richmond, G.; Salmon Ceron, D.; Sax, P.; Scarsella, A.; Sension, M.; Shalit, P.; Sighinolfi, L.; Sloan, L.; Small, C.; Stein, D.; Tashima, K.; Tebas, P.; Torti, C.; Tribble, M.; Troisvallets, D.; Tsoukas, C.; Viciana Fernández, P.; Ward, D.; Wheeler, D.; Wilkin, T.; Yeni, G.-P.; Louise Martin-Carpenter, J.; Uhlenbrauck, Gina

    2014-01-01

    Background. The pilot phase IIb VIKING study suggested that dolutegravir (DTG), a human immunodeficiency virus (HIV) integrase inhibitor (INI), would be efficacious in INI-resistant patients at the 50 mg twice daily (BID) dose. Methods. VIKING-3 is a single-arm, open-label phase III study in which therapy-experienced adults with INI-resistant virus received DTG 50 mg BID while continuing their failing regimen (without raltegravir or elvitegravir) through day 7, after which the regimen was optimized with ≥1 fully active drug and DTG continued. The primary efficacy endpoints were the mean change from baseline in plasma HIV-1 RNA at day 8 and the proportion of subjects with HIV-1 RNA INI-naive subjects receiving DTG 50 mg once daily. Conclusions. DTG 50 mg BID–based therapy was effective in this highly treatment-experienced population with INI-resistant virus. Clinical Trials Registration. www.clinicaltrials.gov (NCT01328041) and http://www.gsk-clinicalstudywww.gsk-clinicalstudyregister.com (112574). PMID:24446523

  9. 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.

  10. Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase study

    OpenAIRE

    Dreyling, Martin; Jurczak, Wojciech; Jerkeman, Mats; Silva, Rodrigo Santucci; Rusconi, Chiara; Trneny, Marek; Offner, Fritz; Caballero, Dolores; Joao, Cristina; Witzens-Harig, Mathias; Hess, Georg; Bence-Bruckler, Isabelle; Cho, Seok-Goo; Bothos, John; Goldberg, Jenna D.

    2016-01-01

    Background: Mantle-cell lymphoma is an aggressive B-cell lymphoma with a poor prognosis. Both ibrutinib and temsirolimus have shown single-agent activity in patients with relapsed or refractory mantle-cell lymphoma. We undertook a phase 3 study to assess the efficacy and safety of ibrutinib versus temsirolimus in relapsed or refractory mantle-cell lymphoma. Methods: This randomised, open-label, multicentre, phase 3 clinical trial enrolled patients with relapsed or refractory mantle-cell l...

  11. Adjunctive lisdexamfetamine dimesylate therapy in adult outpatients with predominant negative symptoms of schizophrenia: open-label and randomized-withdrawal phases.

    Science.gov (United States)

    Lasser, Robert A; Dirks, Bryan; Nasrallah, Henry; Kirsch, Courtney; Gao, Joseph; Pucci, Michael L; Knesevich, Mary A; Lindenmayer, Jean-Pierre

    2013-10-01

    Negative symptoms of schizophrenia (NSS), related to hypodopaminergic activity in the mesocortical pathway and prefrontal cortex, are predictive of poor outcomes and have no effective treatment. Use of dopamine-enhancing drugs (eg, psychostimulants) has been limited by potential adverse effects. This multicenter study examined lisdexamfetamine dimesylate (LDX), a d-amphetamine prodrug, as adjunctive therapy to antipsychotics in adults with clinically stable schizophrenia and predominant NSS. Outpatients with stable schizophrenia, predominant NSS, limited positive symptoms, and maintained on stable atypical antipsychotic therapy underwent a 3-week screening, 10-week open-label adjunctive LDX (20-70 mg/day), and 4-week, double-blind, randomized, placebo-controlled withdrawal. Efficacy measures included a modified Scale for the Assessment of Negative Symptoms (SANS-18) and Positive and Negative Syndrome Scale (PANSS) total and subscale scores. Ninety-two participants received open-label LDX; 69 received double-blind therapy with placebo (n=35) or LDX (n=34). At week 10 (last observation carried forward; last open-label visit), mean (95% confidence interval) change in SANS-18 scores was -12.9 (-15.0, -10.8; P<0.0001). At week 10, 52.9% of participants demonstrated a minimum of 20% reduction from baseline in SANS-18 score. Open-label LDX was also associated with significant improvement in PANSS total and subscale scores. During the double-blind/randomized-withdrawal phase, no significant differences (change from randomization baseline) were found between placebo and LDX in SANS-18 or PANSS subscale scores. In adults with clinically stable schizophrenia, open-label LDX appeared to be associated with significant improvements in negative symptoms without positive symptom worsening. Abrupt LDX discontinuation was not associated with positive or negative symptom worsening. Confirmation with larger controlled trials is warranted. PMID:23756608

  12. 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

    2014-07-01

    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. PMID:24553755

  13. 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.

  14. Effect of renal impairment on the pharmacokinetics of prucalopride: a single- dose open-label Phase I study

    Directory of Open Access Journals (Sweden)

    Smith WB

    2012-12-01

    Full Text Available William B Smith,1 Erik Mannaert,2 Tom Verhaeghe,2 René Kerstens,3 Lieve Vandeplassche,3 Vera Van de Velde41Volunteer Research Group and New Orleans Center for Clinical Research, The University of Tennessee Medical Center, Knoxville, TN, USA; 2Janssen Research and Development, a division of Janssen Pharmaceutica NV, Beerse, Belgium; 3Shire-Movetis NV, Turnhout, Belgium; 4Independent Consultant Clinical Pharmacokinetics, Princeton, NJ, USAObjective: To evaluate the pharmacokinetics of prucalopride in individuals with renal impairment (RI.Methods: This open-label Phase I study (ClinicalTrials.gov identifier: NCT01674192 enrolled men and women aged 18–75 years who were classified by renal function: normal renal function (creatinine clearance ≥ 80 mL/min/1.73 m2, mild RI (50–79 mL/min/1.73 m2, moderate RI (25–49 mL/min/1.73 m2, and severe RI (≤24 mL/min/1.73 m2. All received a single oral dose of prucalopride 2 mg.Results: Thirty-four individuals (normal renal function: 10; mild RI: 8; moderate RI: 7; severe RI: 9 received prucalopride. In all groups, maximum plasma concentration was reached within 2–4 hours. There was no significant difference in exposure (area under the plasma concentration–time curve from time zero to infinity between participants with mild RI and those with normal renal function. However, area under the plasma concentration–time curve from time zero to infinity values were 1.5- and 2.3-fold higher (P = 0.002 and P < 0.001 in patients with moderate RI and severe RI, respectively, than in those with normal renal function. The proportion of total body clearance accounted for by renal clearance was significantly reduced in those with RI.Conclusion: Clinically meaningful reductions in renal clearance were seen in participants with severe RI, which supports a decrease from the standard dose of prucalopride 2 mg daily to 1 mg daily in these individuals.Keywords: renal impairment, pharmacokinetics, prucalopride, safety

  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. Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study

    OpenAIRE

    Cirak, S.; Arechavala-Gomeza, V.; Guglieri, M; Feng, L; Torelli, S.; Anthony, K; Abbs, S; Garralda, M E; Bourke, J; Wells, D J; Dickson, G; Wood, M. J. A.; Wilton, S D; Straub, V.; Kole, R

    2011-01-01

    Summary Background We report clinical safety and biochemical efficacy from a dose-ranging study of intravenously administered AVI-4658 phosphorodiamidate morpholino oligomer (PMO) in patients with Duchenne muscular dystrophy. Method We undertook an open-label, phase 2, dose-escalation study (0·5, 1·0, 2·0, 4·0, 10·0, and 20·0 mg/kg bodyweight) in ambulant patients with Duchenne muscular dystrophy aged 5–15 years with amenable deletions in DMD. Participants had a muscle biopsy before starting ...

  17. Subgroup Analyses from a Phase 3, Open-Label, Randomized Study of Eribulin Mesylate Versus Capecitabine in Pretreated Patients with Advanced or Metastatic Breast Cancer

    Science.gov (United States)

    Twelves, Chris; Awada, Ahmad; Cortes, Javier; Yelle, Louise; Velikova, Galina; Olivo, Martin S.; Song, James; Dutcus, Corina E.; Kaufman, Peter A.

    2016-01-01

    PURPOSE AND METHODS Our secondary analyses compared survival with eribulin versus capecitabine in various patient subgroups from a phase 3, open-label, randomized study. Eligible women aged ≥18 years with advanced/metastatic breast cancer and ≤3 prior chemotherapies (≤2 for advanced/metastatic disease), including an anthracycline and taxane, were randomized 1:1 to intravenous eribulin mesylate 1.4 mg/m2 on days 1 and 8 or twice-daily oral capecitabine 1250 mg/m2 on days 1–14 (21-day cycles). RESULTS In the intent-to-treat population (eribulin 554 and capecitabine 548), overall survival appeared longer with eribulin than capecitabine in various subgroups, including patients with human epidermal growth factor receptor 2-negative (15.9 versus 13.5 months, respectively), estrogen receptor-negative (14.4 versus 10.5 months, respectively), and triple-negative (14.4 versus 9.4 months, respectively) disease. Progression-free survival was similar between the treatment arms. CONCLUSIONS Patients with advanced/metastatic breast cancer and human epidermal growth factor receptor 2-, estrogen receptor-, or triple-negative disease may gain particular benefit from eribulin as first-, second-, and third-line chemotherapies. TRIAL REGISTRATION (PRIMARY STUDY) This study reports the subgroup analyses of eribulin versus capecitabine from a phase 3, open-label, randomized study (www.clinicaltrials.gov; ClinicalTrials.gov identifier: NCT00337103). PMID:27398025

  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. Phase II, Open-Label, Randomized Trial of the MEK 1/2 Inhibitor Selumetinib as Monotherapy versus Temozolomide in Patients with Advanced Melanoma

    DEFF Research Database (Denmark)

    Kirkwood, John M; Bastholt, Lars; Robert, Caroline;

    2011-01-01

    PURPOSE: To compare the efficacy and tolerability of the MEK 1/2 inhibitor selumetinib versus temozolomide in chemotherapy-naïve patients with unresectable stage III/IV melanoma.Methods: This phase II, open-label, multicenter, randomized, parallel-group study examined the effect of 100 mg oral...... selumetinib twice daily in 28-day cycles versus oral temozolomide (200 mg/m2/day for 5 days, then 23 days off treatment). The primary endpoint was progression-free survival.RESULTS: Two hundred patients were randomized. Progression-free survival did not differ significantly between selumetinib...... and temozolomide (median time to event 78 and 80 days, respectively; hazard ratio, 1.07; 80% confidence interval, 0.86-1.32). Objective response was observed in six (5.8%) patients receiving selumetinib and nine (9.4%) patients in the temozolomide group. Among patients with BRAF mutations, objective responses were...

  20. Adjunctive triple chronotherapy (combined total sleep deprivation, sleep phase advance, and bright light therapy) rapidly improves mood and suicidality in suicidal depressed inpatients: an open label pilot study.

    Science.gov (United States)

    Sahlem, Gregory L; Kalivas, Benjamin; Fox, James B; Lamb, Kayla; Roper, Amanda; Williams, Emily N; Williams, Nolan R; Korte, Jeffrey E; Zuschlag, Zachary D; El Sabbagh, Salim; Guille, Constance; Barth, Kelly S; Uhde, Thomas W; George, Mark S; Short, E Baron

    2014-12-01

    Previous studies have demonstrated that combined total sleep deprivation (Wake therapy), sleep phase advance, and bright light therapy (Triple Chronotherapy) produce a rapid and sustained antidepressant effect in acutely depressed individuals. To date no studies have explored the impact of the intervention on unipolar depressed individuals with acute concurrent suicidality. Participants were suicidal inpatients (N = 10, Mean age = 44 ± 16.4 SD, 6F) with unipolar depression. In addition to standard of care, they received open label Triple Chronotherapy. Participants underwent one night of total sleep deprivation (33-36 h), followed by a three-night sleep phase advance along with four 30-min sessions of bright light therapy (10,000 lux) each morning. Primary outcome measures included the 17 item Hamilton depression scale (HAM17), and the Columbia Suicide Severity Rating Scale (CSSRS), which were recorded at baseline prior to total sleep deprivation, and at protocol completion on day five. Both HAM17, and CSSRS scores were greatly reduced at the conclusion of the protocol. HAM17 scores dropped from a mean of 24.7 ± 4.2 SD at baseline to a mean of 9.4 ± 7.3 SD on day five (p = .002) with six of the ten individuals meeting criteria for remission. CSSRS scores dropped from a mean of 19.5 ± 8.5 SD at baseline to a mean of 7.2 ± 5.5 SD on day five (p = .01). The results of this small pilot trial demonstrate that adjunctive Triple Chronotherapy is feasible and tolerable in acutely suicidal and depressed inpatients. Limitations include a small number of participants, an open label design, and the lack of a comparison group. Randomized controlled studies are needed. PMID:25231629

  1. Safety and tolerability of azilsartan medoxomil in subjects with essential hypertension: a one-year, phase 3, open-label study.

    Science.gov (United States)

    Handley, Alison; Lloyd, Eric; Roberts, Andrew; Barger, Bruce

    2016-01-01

    This 56-week phase 3, open-label, treat-to-target study, involving 2 consecutive, non-randomized cohorts, evaluated the safety and tolerability of azilsartan medoxomil (AZL-M) in essential hypertension (mean baseline blood pressure [BP] 152/100 mmHg). All subjects (n = 669) initiated AZL-M 40 mg QD, force-titrated to 80 mg QD at week 4, if tolerated. From week 8, subjects could receive additional medications, starting with chlorthalidone (CLD) 25 mg QD (Cohort 1) or hydrochlorothiazide (HCTZ) 12.5-25 mg QD (Cohort 2), if required, to reach BP targets. Adverse events (AEs) were reported in 75.9% of subjects overall in the two cohorts (73.8% Cohort 1, 78.5% Cohort 2). The most common AEs were dizziness (14.3%), headache (9.9%) and fatigue (7.2%). Transient serum creatinine elevations were more frequent with add-on CLD. Clinic systolic/diastolic BP (observed cases at week 56) decreased by 25.2/18.4 mmHg (Cohort 1) and 24.2/17.9 mmHg (Cohort 2). These results demonstrate that AZL-M is well tolerated over the long term and provides stable BP improvements when used in a treat-to-target BP approach with thiazide-type diuretics. PMID:26817604

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

    International Nuclear Information System (INIS)

    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 http://clinicaltrials.gov/show/NCT00326469; EU Clinical Trial Register EudraCT no 2004-002871-18

  3. An open-labeled, randomized, multicenter phase Ⅱa study of gambogic acid injection for advanced malignant tumors

    Institute of Scientific and Technical Information of China (English)

    CHI Yihebali; ZHAN Xiao-kai; YU Hao; XIE Guang-ru; WANG Zhen-zhong; XIAO Wei; WANG Yong-gang

    2013-01-01

    Background Gambogic acid is a pure active compound isolated from the traditional Chinese medicinal plant gamboge (Garcinia morella Desv.).Based on the preliminary results of a phase I study,this phase Ila study compared the efficacy and safety of different dosage schedules of gambogic acid in patients with advanced malignant tumors.Methods Patients with advanced or metastases cancer who had not received any effective routine conventional treatment or who had failed to respond to the existing conventional treatment were randomly assigned to receive either 45 mg/m2 gambogic acid intravenously from Days 1 to 5 of a 2-week cycle (Group A),or 45 mg/m2 every other day for a total of five times during a 2-week cycle (Group B).The primary endpoint was objective response rate (ORR).Results Twenty-one patients assigned to Group A and 26 to Group B were included in the final analysis.The ORRs were 14.3% in Group A and 0% in Group B.It was not possible to analyze the significant difference because one of the values was zero.The disease control rates (DCRs) were 76.2% in Group A and 61.5% in Group B (P=-0.0456).The observed adverse reactions were mostly Grades Ⅰ and Ⅱ,and occurred in most patients after administration of the trial drug.There was no significant difference in the incidence of adverse reactions between the two arms.Conclusions The preliminary results of this phase Ila exploratory study suggest that gambogic acid has a favorable safety profile when administered at 45 mg/m2.The DCR was greater in patients receiving gambogic acid on Days 1-5 of a 2-week cycle,but the incidence of adverse reactions was similar irrespective of the administration schedule.

  4. 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.

  5. 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

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

    International Nuclear Information System (INIS)

    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. 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. 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. 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. NCT00444782

  7. 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.

  8. Pharmacokinetics of aclidinium bromide/formoterol fumarate fixed-dose combination compared with individual components: A phase 1, open-label, single-dose study.

    Science.gov (United States)

    Fuhr, Rainard; Leselbaum, Anne; Aubets, Jordi

    2016-03-01

    Inhaled, long-acting bronchodilators represent a cornerstone of maintenance treatment for chronic obstructive pulmonary disease (COPD). Aclidinium bromide/formoterol fumarate 400/12 μg fixed-dose combination (FDC) has recently been licensed for use in adults with COPD in the European Union. This phase 1, randomized, open-label, 3-way, complete crossover, single-dose study assessed the pharmacokinetics, safety, and tolerability of an FDC, aclidinium bromide 400 μg, and formoterol fumarate 12 μg, all administered via Genuair™ to 30 healthy subjects. The rate and extent of absorption were comparable for aclidinium/formoterol FDC and individual monotherapies; aclidinium/formoterol FDC and aclidinium alone: Cmax , 270 and 215 pg/mL, respectively; AUC0-t , 229 and 222 pg · h/mL, respectively; aclidinium/formoterol FDC and formoterol alone: Cmax , 11 and 9.3 pg/mL, respectively; AUC, 36 and 32.4 pg · h/mL, respectively. There were no major differences in relative bioavailability between the combination and monotherapies: the aclidinium Cmax and AUC0-t were 26% and 3% higher, respectively, with aclidinium/formoterol FDC compared with aclidinium alone, and 18% and 11% higher, respectively, compared with formoterol alone. Aclidinium/formoterol FDC was well tolerated; the incidence of adverse events was low and similar to the monotherapies. Aclidinium/formoterol FDC was not associated with any major differences in rate and extent of absorption or relative bioavailability compared with monotherapies. PMID:27138024

  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

    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...

  10. 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, M R; Lindahl, Lise Maria; Gniadecki, R;

    2012-01-01

    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...

  11. Driving Ability in Patients with Severe Chronic Low Back or Osteoarthritis Knee Pain on Stable Treatment with Tapentadol Prolonged Release: A Multicenter, Open-label, Phase 3b Trial

    OpenAIRE

    Sabatowski, Rainer; Scharnagel, Rüdiger; Gyllensvärd, Anne; Steigerwald, Ilona

    2014-01-01

    Introduction Strong centrally acting analgesics, including tapentadol prolonged release (PR), have demonstrated efficacy for the management of non-malignant, chronic pain. Maintaining patient independence, including the ability to drive safely, is a key goal of long-term analgesic therapy. This multicenter, open-label, phase 3b trial evaluated the effects of tapentadol PR on driving ability. Methods This study included patients who had completed previous tapentadol PR trials for severe low ba...

  12. Effectiveness and safety of tapentadol prolonged release with tapentadol immediate release on-demand for the management of severe, chronic osteoarthritis-related knee pain: results of an open-label, phase 3b study

    OpenAIRE

    Steigerwald I; Calvo-Alén J; Balblanc JC; Kujawa J; Müller M

    2012-01-01

    Ilona Steigerwald,1 Matthias Müller,1 Jolanta Kujawa,2 Jean-Charles Balblanc,3 Jaime Calvo-Alén,41Medical Affairs Europe & Australia, Grünenthal GmbH, Aachen, Germany; 2Medical University of Lodz, Medical Rehabilitation Clinic, Lodz, Poland; 3Department of Rheumatology, General Hospital of Belfort, Belfort, France; 4Hospital Universitario Sierrallana and IFIMAV Research Institute, Universidad de Cantabria, Cantabria, SpainAbstract: This open-label, phase 3...

  13. 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

  14. Patient adherence to and tolerability of self-administered interferon β-1a using an electronic autoinjection device: a multicentre, open-label, phase IV study

    Directory of Open Access Journals (Sweden)

    Lugaresi Alessandra

    2012-03-01

    Full Text Available Abstract Background Achieving good adherence to self-injected treatments for multiple sclerosis can be difficult. Injection devices may help to overcome some of the injection-related barriers to adherence that can be experienced by patients. We sought to assess short-term adherence to, and tolerability of, interferon (IFN β-1a administered via electronic autoinjection device in patients with relapsing-remitting multiple sclerosis (RRMS. Methods BRIDGE (RebiSmart to self-inject Rebif serum-free formulation in a multidose cartridge was a 12-week, multicentre, open-label, single-arm, observational, Phase IV study in which patients self-administered IFN β-1a (titrated to 44 μg, subcutaneously (sc, three times weekly, via electronic autoinjection device. Patients were assessed at baseline and 4-weekly intervals to Week 12 or early termination (ET for: physical examinations; diary card completion (baseline, Weeks 4, 8 only; neurological examinations (baseline, Week 12/ET only; MS Treatment Concern Questionnaire (MSTCQ; Weeks 4, 8, 12 only; Convenience Questionnaire (Week 12 only; Hospital Anxiety and Depression Scale (HADS; and Paced Auditory Serial Addition Task (PASAT; baseline only. Adherence was defined as administration of ≥ 80% of scheduled injections, recorded by the autoinjection device. Results Overall, 88.2% (105/119; intent-to-treat population of patients were adherent; 67.2% (80/119 administered all scheduled injections. Medical reasons accounted for 35.6% (31/87 of missed injections, forgetfulness for 20.6% (18/87. Adherence did not correlate with baseline Expanded Disability Status Scale (P = 0.821 or PASAT (P = 0.952 scores, or pre-study therapy (P = 0.303. No significant changes (baseline-Week 12 in mean HADS depression (P = 0.482 or anxiety (P = 0.156 scores were observed. 'Overall convenience' was the most important reported benefit of the autoinjection device. Device features associated with handling and ease of use were highly

  15. 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

  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. 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

  18. Infliximab therapy for intestinal, neurological, and vascular involvement in Behcet disease: Efficacy, safety, and pharmacokinetics in a multicenter, prospective, open-label, single-arm phase 3 study.

    Science.gov (United States)

    Hibi, Toshifumi; Hirohata, Shunsei; Kikuchi, Hirotoshi; Tateishi, Ukihide; Sato, Noriko; Ozaki, Kunihiko; Kondo, Kazuoki; Ishigatsubo, Yoshiaki

    2016-06-01

    Behçet disease (BD) is a multisystem disease associated with a poor prognosis in cases of gastrointestinal, neurological, or vascular involvement. We conducted a multicenter, prospective, open-label, single-arm phase 3 study to determine the efficacy, safety, and pharmacokinetics of infliximab (IFX) in BD patients with these serious complications who had displayed poor response or intolerance to conventional therapy.IFX at 5 mg/kg was administered to 18 patients (11 intestinal BD, 3 neurological BD [NBD], and 4 vascular BD [VBD]) at weeks 0, 2, and 6 and every 8 weeks thereafter until week 46. In patients who showed inadequate responses to IFX after week 30, the dose was increased to 10 mg/kg. We then calculated the percentage of complete responders according to the predefined criteria depending on the symptoms and results of examinations (ileocolonoscopy, brain magnetic resonance imaging, computed tomography angiography, positron emission tomography, cerebrospinal fluid, or serum inflammatory markers), exploring the percentage of complete responders at week 30 (primary endpoint).The percentage of complete responders was 61% (11/18) at both weeks 14 and 30 and remained the same until week 54. Intestinal BD patients showed improvement in clinical symptoms along with decrease in C-reactive protein (CRP) levels after week 2. Consistently, scarring or healing of the principal ulcers was found in more than 80% of these patients after week 14. NBD patients showed improvement in clinical symptoms, imaging findings, and cerebrospinal fluid examinations. VBD patients showed improvement in clinical symptoms after week 2 with reductions in CRP levels and erythrocyte sedimentation rate. Imaging findings showed reversal of inflammatory changes in 3 of the 4 VBD patients. Irrespective of the type of BD, all patients achieved improvement in quality of life, leading to the dose reduction or withdrawal of steroids. IFX dose was increased to 10 mg/kg in 3 intestinal BD

  19. 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.

  20. 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.

  1. Safety and hemostatic efficacy of fibrin pad in partial nephrectomy: Results of an open-label Phase I and a randomized, standard-of-care-controlled Phase I/II study

    Directory of Open Access Journals (Sweden)

    Nativ Ofer

    2012-11-01

    Full Text Available Abstract Background Bleeding severity, anatomic location, tissue characteristics, and visibility are common challenges encountered while managing intraoperative bleeding, and conventional hemostatic measures (suture, ligature, and cautery may sometimes be ineffective or impractical. While topical absorbable hemostats (TAH are useful hemostatic adjuvants, each TAH has associated disadvantages. Methods We evaluated the safety and hemostatic efficacy of a new advanced biologic combination product―fibrin pad―to potentially address some gaps associated with TAHs. Fibrin pad was assessed as adjunctive hemostat in open partial nephrectomy in single-center, open-label, Phase I study (N = 10, and as primary hemostat in multicenter, single-blind, randomized, standard-of-care (SOC-controlled Phase I/II study (N = 7 in Israel. It was used to control mild-to-moderate bleeding in Phase I and also spurting arterial bleeding in Phase I/II study. Phase I study assessed safety and Phase I/II study, proportion of successes at 10 min following randomization, analyzed by Fisher exact tests at 5% significance level. Results Phase I (N = 10: All patients completed the study. Hemostasis was achieved within 3–4 min (average = 3.1 min of a single application in all patients. Fibrin pad was found to be safe for human use, with no product-related adverse events reported. Phase I/II (N = 7: Hemostatic success at 10 min (primary endpoint was achieved in 3/4 patients treated with fibrin pad versus 0/3 patients treated with SOC. No clinically significant change in laboratory or coagulation parameters was recorded, except a case of post-procedural hemorrhage with fibrin pad, which was considered serious and related to the fibrin pad treatment, and required re-operation. Although Data Safety Monitoring Board authorized trial continuation, the sponsor decided against proceeding toward an indication for primary treatment of severe arterial

  2. A phase II, multicenter, open-label study evaluating dosing and preliminary safety and efficacy of canakinumab in systemic juvenile idiopathic arthritis with active systemic features

    NARCIS (Netherlands)

    Ruperto, Nicolino; Quartier, Pierre; Wulffraat, Nico; Woo, Patricia; Ravelli, Angelo; Mouy, Richard; Bader-Meunier, Brigitte; Vastert, Sebastiaan J.; Noseda, Emanuele; D'Ambrosio, Daniele; Lecot, Jean; Chakraborty, Abhijit; Martini, Alberto; Chioato, Andrea

    2012-01-01

    Objective To assess dosing, preliminary safety, and efficacy of canakinumab, a fully human antiinterleukin-1 beta (antiIL-1 beta) antibody, in children with systemic juvenile idiopathic arthritis (JIA) and active systemic features. Methods. In this phase II, multicenter, openlabel, dosage-escalation

  3. 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.

  4. Adjunctive Triple Chronotherapy (Combined Total Sleep Deprivation, Sleep Phase Advance, and Bright Light Therapy) Rapidly Improves Mood and Suicidality in Suicidal Depressed Inpatients: An Open Label Pilot Study

    OpenAIRE

    Sahlem, Gregory L.; Kalivas, Benjamin; Fox, James B.; Lamb, Kayla; Roper, Amanda; Williams, Emily N.; Williams, Nolan R.; Korte, Jeffrey E.; Zuschlag, Zachary D.; El Sabbagh, Salim; Guille, Constance; Barth, Kelly S.; Uhde, Thomas W.; George, Mark S.; Short, E. Baron

    2014-01-01

    Previous studies have demonstrated that combined total sleep deprivation (Wake therapy), sleep phase advance, and bright light therapy (Triple Chronotherapy) produce a rapid and sustained antidepressant effect in acutely depressed individuals. To date no studies have explored the impact of the intervention on unipolar depressed individuals with acute concurrent suicidality. Participants were suicidal inpatients (N=10, Mean age=44±16.4SD, 6F) with unipolar depression. In addition to standard o...

  5. 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. PMID:24950666

  6. Long-term Escitalopram Treatment in Korean Patients with Panic Disorder: A Prospective, Naturalistic, Open-label, Multicenter Trial

    OpenAIRE

    Choi, Kwan-Woo; Woo, Jong-Min; Kim, Youl-Ri; Lee, Seung-Hwan; Lee, Sang-Yeol; Kim, Eui-Jung; Chung, Sang-Keun; Kang, Eun-Ho; Lee, Jae-Hon; Yu, Bum-Hee

    2012-01-01

    Objective Panic disorder is characterized by recurrent panic attacks, persistent concerns about additional attacks, and worry about the implications of the attack or significant changes in behavior related to the attacks. We examined the efficacy of 24-week naturalistic, open-label escitalopram treatment in terms of the response and remission rates and functional disability in 119 adult Korean patients with panic disorder from 6 clinical centers in South Korea. Methods Clinical severity and f...

  7. Cilengitide with metronomic temozolomide, procarbazine, and standard radiotherapy in patients with glioblastoma and unmethylated MGMT gene promoter in ExCentric, an open-label phase II trial.

    Science.gov (United States)

    Khasraw, Mustafa; Lee, Adrian; McCowatt, Sally; Kerestes, Zoltan; Buyse, Marc E; Back, Michael; Kichenadasse, Ganessan; Ackland, Stephen; Wheeler, Helen

    2016-05-01

    Newly diagnosed glioblastoma multiforme with unmethylated MGMT promoter has a poor prognosis, with a median survival of 12 months. This phase II study investigated the efficacy and safety of combining the selective integrin inhibitor cilengitide with a combination of metronomic temozolomide and procarbazine for these patients. Eligible patients (newly diagnosed, histologically confirmed supratentorial glioblastoma with unmethylated MGMT promoter) were entered into this multicentre study. Cilengitide (2000 mg IV twice weekly) was commenced 1 week prior to radiotherapy combined with daily temozolomide (60 mg/m(2)) and procarbazine (50 or 100 mg) and, after 4 weeks' break, followed by six adjuvant cycles of temozolomide (50-60 mg/m(2)) and procarbazine (50 or 100 mg) on days 1-20, every 28 days. Cilengitide was continued for up to 12 months or until disease progression or unacceptable toxicity. The primary endpoint for efficacy was a 12-month overall survival rate of 65 %. Twenty-nine patients completed study treatment. Sixteen patients survived for 12 months or more, an overall survival rate of 55 %. The median overall survival was 14.5 months (95 % CI 11.1-19.6) and the median progression-free survival was 7.4 months (95 % CI 6.1-8). Cilengitide combined with metronomic temozolomide and procarbazine in MGMT-promoter unmethylated glioblastoma did not improve survival compared with historical data and does not warrant further investigation. PMID:26935578

  8. 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.

  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. Safety and efficacy of everolimus in Chinese patients with metastatic renal cell carcinoma resistant to vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy: an open-label phase 1b study

    International Nuclear Information System (INIS)

    In China, there are currently no approved therapies for the treatment of metastatic renal cell carcinoma (mRCC) following progression with vascular endothelial growth factor (VEGF)-targeted agents. In the phase 3 RECORD-1 trial, the mammalian target of rapamycin (mTOR) inhibitor everolimus afforded clinical benefit with good tolerability in Western patients with mRCC whose disease had progressed despite VEGF receptor-tyrosine kinase inhibitor (VEGFr-TKI) therapy. This phase 1b study was designed to further evaluate the safety and efficacy of everolimus in VEGFr-TKI-refractory Chinese patients with mRCC. An open-label, multicenter phase 1b study enrolled Chinese patients with mRCC who were intolerant to, or progressed on, previous VEGFr-TKI therapy (N = 64). Patients received everolimus 10 mg daily until objective tumor progression (according to RECIST, version 1.0), unacceptable toxicity, death, or study discontinuation for any other reason. The final data analysis cut-off date was November 30, 2011. A total of 64 patients were included in the study. Median age was 52 years (range, 19–75 years) and 69% of patients were male. Median duration of everolimus therapy was 4.1 months (range, 0.0-16.1 months). Expected known class-effect toxicities related to mTOR inhibitor therapy were observed, including anemia (64%), hypertriglyceridemia (55%), mouth ulceration (53%), hyperglycemia (52%), hypercholesterolemia (50%), and pulmonary events (31%). Common grade 3/4 adverse events were anemia (20%), hyperglycemia (13%), increased gamma-glutamyltransferase (11%), hyponatremia (8%), dyspnea (8%), hypertriglyceridemia (6%), and lymphopenia (6%). Median PFS was 6.9 months (95% CI, 3.7-12.5 months) and the overall tumor response rate was 5% (95% CI, 1-13%). The majority of patients (61%) had stable disease as their best overall tumor response. Safety and efficacy results were comparable to those of the RECORD-1 trial. Everolimus is generally well tolerated and provides clinical

  11. Gemcitabine, oxaliplatin, levofolinate, 5-fluorouracil, granulocyte-macrophage colony-stimulating factor, and interleukin-2 (GOLFIG) versus FOLFOX chemotherapy in metastatic colorectal cancer patients: the GOLFIG-2 multicentric open-label randomized phase III trial.

    Science.gov (United States)

    Correale, Pierpaolo; Botta, Cirino; Rotundo, Maria S; Guglielmo, Annamaria; Conca, Raffaele; Licchetta, Antonella; Pastina, Pierpaolo; Bestoso, Elena; Ciliberto, Domenico; Cusi, Maria G; Fioravanti, Antonella; Guidelli, Giacomo M; Bianco, Maria T; Misso, Gabriella; Martino, Elodia; Caraglia, Michele; Tassone, Pierfrancesco; Mini, Enrico; Mantovani, Giovanni; Ridolfi, Ruggero; Pirtoli, Luigi; Tagliaferri, Pierosandro

    2014-01-01

    The GOLFIG-2 phase III trial was designed to compare the immunobiological activity and antitumor efficacy of GOLFIG chemoimmunotherapy regimen with standard FOLFOX-4 chemotherapy in frontline treatment of metastatic colorectal cancer (mCRC) patients. This trial was conceived on the basis of previous evidence of antitumor and immunomodulating activity of the GOLFIG regimen in mCRC. GOLFIG-2 is a multicentric open/label phase III trial (EUDRACT: 2005-003458-81). Chemo-naive mCRC patients were randomized in a 1:1 ratio to receive biweekly standard FOLFOX-4 or GOLFIG [gemcitabine (1000 mg/m(2), day 1); oxaliplatin (85 mg/m(2), day 2); levofolinate (100 mg/m(2), days 1-2), 5-fluorouracil (5-FU) (400 mg/m(2) in bolus followed by 24 h infusion at 800 mg/m(2),days 1-2), sc. GM-CSF (100 μg, days 3-7); sc. aldesleukin (0·5 MIU bi-daily, days 8-14 and 17-30)] treatments. The study underwent early termination because of poor recruitment in the control arm. After a median follow-up of 43.83 months, GOLFIG regimen showed superiority over FOLFOX in terms of progression-free survival [median 9·23 (95% confidence interval (CI), 6·9-11.5) vs. median 5.70 (95% CI, 3.38-8.02) months; hazard ratio (HR): 0.52 (95% CI, 0.35-0.77), P=0·002] and response rate [66.1% (95% CI, 0.41-0.73) vs. 37·0% (95% CI, 0.28-0.59), P=0.002], with a trend to longer survival [median 21.63 (95% CI, 18.09-25.18) vs. 14.57 mo (95% CI, 9.07-20.07); HR: 0·79 (95% CI, 0.52-1.21); P=0.28]. Patients in the experimental arm showed higher incidence of non-neutropenic fever (18.5%), autoimmunity signs (18.5%), an increase in the number of monocytes, eosinophils, CD4(+) T lymphocytes, natural killer cells, and a decrease in immunoregulatory (CD3(+)CD4(+)CD25(+)FoxP3(+)) T cells. Taken together, these findings provide proof-of-principle that GOLFIG chemoimmunotherapy may represent a novel reliable option for first-line treatment of mCRC. PMID:24316553

  12. 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

    OpenAIRE

    Récher, Christian; Coiffier, Bertrand; Haioun, Corinne; Molina, Thierry Jo; Fermé, Christophe; Casasnovas, Olivier; Thièblement, Catherine; Bosly, André; LAURENT, GUY; Morschhauser, Franck; Ghesquières, Hervé; Jardin, Fabrice; Bologna, Serge; Fruchart, Christophe; Corront, Bernadette

    2011-01-01

    Background The outcome of diff use 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 benefi t provided by a dose-intensive immunochemotherapy regimen plus rituximab compared with standard treatment plus rituximab. Methods We did an open-label randomised trial comparing dose-intensive rituximab, doxorubicin, cyclo phosphamide, ...

  13. An open-label phase 2 trial of dabrafenib plus trametinib in patients with previously treated BRAF V600E–mutant metastatic non-small cell lung cancer

    Science.gov (United States)

    Planchard, David; Besse, Benjamin; Groen, Harry J M; Souquet, Pierre-Jean; Quoix, Elisabeth; Baik, Christina S; Barlesi, Fabrice; Kim, Tae Min; Mazieres, Julien; Novello, Silvia; Rigas, James R; Upalawanna, Allison; D’Amelio, Anthony M; Zhang, Pingkuan; Mookerjee, Bijoyesh; Johnson, Bruce E

    2016-01-01

    Background BRAF mutations act as an oncogenic driver via the mitogen-activated protein kinase (MAPK) pathway in non-small cell lung cancer (NSCLC). BRAF inhibition has demonstrated antitumor activity in patients with BRAF V600E (Val600Glu)–mutant NSCLC. Dual MAPK pathway inhibition with BRAF and MEK inhibitors in BRAF V600E–mutant NSCLC may improve efficacy over BRAF-inhibitor monotherapy based on observations in BRAF V600–mutant melanoma. Methods In this phase 2, multicenter, nonrandomized, open-label study of patients with pretreated metastatic BRAF V600E–mutant NSCLC, antitumor activity and safety of oral dabrafenib (150 mg twice daily) plus oral trametinib (2 mg once daily) were evaluated. Adult patients (≥ 18 years) with documented progression following at least one prior platinum-based chemotherapy and no more than three prior systemic anticancer therapies were enrolled. Patients with prior BRAF or MEK inhibitor treatment were ineligible. Patients with brain metastases were permitted to enroll only if the lesions were asymptomatic, untreated (or stable > 3 weeks after local therapy if treated), and measured < 1 cm. The primary endpoint was investigator-assessed overall response, which was assessed by intention-to-treat in the protocol-defined population (≥ second-line); safety was also assessed in this population. The study is ongoing but no longer recruiting patients. This trial is registered with ClinicalTrials.gov, number NCT01336634. Findings Fifty-seven patients previously treated with systemic chemotherapy for metastatic BRAF V600E–mutant NSCLC were enrolled. The investigator-assessed overall response was 63·2% (36 of 57; 95% CI 49·3–75·6). Serious adverse events were reported in 32 (56%) of 57 patients and included pyrexia (16%; 9 of 57), anemia (5%; 3 of 57), confusional state (4%; 2 of 57), decreased appetite (4%; 2 of 57), hemoptysis (4%; 2 of 57), hypercalcemia (4%; 2 of 57), nausea (4%; 2 of 57), and cutaneous squamous cell

  14. Effectiveness and safety of tapentadol prolonged release with tapentadol immediate release on-demand for the management of severe, chronic osteoarthritis-related knee pain: results of an open-label, phase 3b study

    Directory of Open Access Journals (Sweden)

    Steigerwald I

    2012-06-01

    Full Text Available Ilona Steigerwald,1 Matthias Müller,1 Jolanta Kujawa,2 Jean-Charles Balblanc,3 Jaime Calvo-Alén,41Medical Affairs Europe & Australia, Grünenthal GmbH, Aachen, Germany; 2Medical University of Lodz, Medical Rehabilitation Clinic, Lodz, Poland; 3Department of Rheumatology, General Hospital of Belfort, Belfort, France; 4Hospital Universitario Sierrallana and IFIMAV Research Institute, Universidad de Cantabria, Cantabria, SpainAbstract: This open-label, phase 3b study (ClinicalTrials.gov Identifier: NCT00983073 evaluated the effectiveness, and tolerability of tapentadol for severe, chronic osteoarthritis knee pain that was inadequately managed with World Health Organization (WHO Step I or II analgesics or co-analgesics, or that was not treated with regular analgesics. Prior to starting study treatment, patients discontinued any WHO Step II analgesics, while Step I analgesics and/or co-analgesics were continued at the same dose. Patients received tapentadol prolonged release (50–250 mg bid during a 5-week titration period and a 7-week maintenance period. Doses of tapentadol immediate release 50 mg (≤twice/day; ≥4 hours apart were permitted throughout the study (total daily dose of tapentadol prolonged and immediate release, ≤250 mg bid. The primary endpoint was the change in pain intensity on an 11-point numerical rating scale-3 (NRS-3; recalled average pain intensity [11-point NRS] during the last 3 days from baseline to Week 6, using the last observation carried forward (LOCF to impute missing pain intensity scores. The mean (standard deviation change from baseline to Week 6 (LOCF in pain intensity was -3.4 (2.10; P < 0.0001 for all patients evaluated for effectiveness (n = 195. Significant decreases in pain intensity were also observed at Weeks 6, 8, and 12 (all P < 0.0001 using observed-case analysis. Corresponding significant improvements from baseline to Weeks 6 and 12 were observed in the Western Ontario and McMaster Universities

  15. 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

  16. Simplification to atazanavir/ritonavir+lamivudine in virologically suppressed HIV-infected patients: 24-weeks interim analysis from ATLAS-M trial

    Directory of Open Access Journals (Sweden)

    Massimiliano Fabbiani

    2014-11-01

    Full Text Available Introduction: We report interim 24-weeks efficacy data of ATLAS-M trial, a phase IV, multicentre, open-label, randomized study designed to show 48-weeks, non-inferior efficacy (margin of −12% of treatment simplification to atazanavir/ritonavir (ATV/r+lamivudine (3TC versus maintaining 3-drugs ATV/r-based cART. Methods: Subjects on ATV/r+2 NRTIs, without previous treatment failure (TF, with HIV-RNA 3 months and CD4>200 cells/mm3 for >6 months were eligible. At baseline, patients were randomized to switch to ATV/r+3TC (arm one or to maintain the original 3-drug regimen (arm two. Primary endpoint: proportion of patients free of TF at week 48. TF was defined as treatment modification for any reason, including virological failure (VF=two consecutive HIV-RNA>50 copies/mL or a single value >1000 copies/mL. Enrollment of 266 patients was planned. Results: A total of 266 patients (78% males, median age 44 years, median CD4 603 cells/µL, 79% treated with a tenofovir-containing backbone were enrolled. At the time of analysis, 24 weeks data were available for 84 and 87 patients in arm one and two, respectively. At baseline, subjects in the two arms did not differ for the main characteristics. At 24 weeks, at the intention to treat analysis the proportion of patients free of TF was 91.7% (95% CI 85.8–97.6 and 85.1% (95% CI 77.6–92.6 in arm one and two, respectively (difference +6.6%, 95% CI −2.9/+16.1. VF was observed in two patients randomized to arm one (one at baseline, before treatment simplification and one to arm two without resistance mutations. Clinical and laboratory adverse events occurred at similar rates in the two arms. At week 24, patients in arm one showed a greater increase in CD4 (mean change +90 vs +10 cells/µL, p=0.007. A greater increase in total cholesterol (+18 vs −2 mg/dL, p<0.001, HDL (+4 vs +0 mg/dL, p=0.001 and LDL (+12 vs +0 mg/dL, p=0.001 was also observed in arm one without differences in other lipid parameters. Renal

  17. 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. PMID:26754331

  18. 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

  19. 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

  20. 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

  1. Efficacy of melflufen, a peptidase targeted therapy, and dexamethasone in an ongoing open-label phase 2a study in patients with relapsed and relapsed-refractory multiple myeloma (RRMM) including an initial report on progression free survival

    DEFF Research Database (Denmark)

    Voorhees, P. M.; Magarotto, V.; Sonneveld, P.;

    2015-01-01

    and produces a 20 fold higher intracellular concentration of alkylating moieties compared with melphalan. Methods: Melflufen is evaluated in combination with dexamethasone (dex) 40 mg weekly in an ongoing Phase 1/2a study. RRMM patients with measurable disease and at least 2 prior lines of therapy are eligible...... (NCT01897714). Phase 1 established the maximum tolerated dose (MTD) of melflufen to be 40 mg every 3 weeks in combination with low dose dex. The primary objective of Phase 2a is the overall response rate and safety of the MTD in a total of 55 patients. Response was investigator assessed at the end...... of each cycle by IMWG criteria. Here we present the Phase 2 data as of 14 July 2015 data-cut. Results: Thirty-one patients were dosed at the MTD. The median time from initial diagnosis to first dose of melflufen was 6 years (1-15). The median number of prior therapies was 4 (2-9). 97% of patients were...

  2. A Phase I, open-label, randomized, crossover study in three parallel groups to evaluate the effect of Rifampicin, Ketoconazole, and Omeprazole on the pharmacokinetics of THC/CBD oromucosal spray in healthy volunteers

    OpenAIRE

    Stott, Colin; White, Linda; Wright, Stephen; Wilbraham, Darren; Guy, Geoffrey

    2013-01-01

    Abstract This Phase I study aimed to assess the potential drug-drug interactions (pharmacokinetic [PK] and safety profile) of Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (Sativex ®, nabiximols) in combination with cytochrome P450 (CYP450) inducer (rifampicin) or inhibitors (ketoconazole or omeprazole). Thirty-six healthy male subjects were divided into three groups of 12, and then randomized to one of two treatment sequences per group. Subjects received four sprays of THC...

  3. European Organization for Research and Treatment of Cancer (EORTC) open label phase II study on glufosfamide administered as a 60-minute infusion every 3 weeks in recurrent glioblastoma multiforme

    OpenAIRE

    Bent, Martin; Stupp, Roger; Lacombe, Denis; Desir, J.P.; Lesimple, T; Dittrich, Christian; Baron, B.; Fumoleau, Pierre; de Jonge, Maja; Brandes, Alba; Oliveira, J.,; Frenay, Marc; Chollet, P; Schuessler, M.; Carpentier, A F

    2003-01-01

    textabstractBACKGROUND: Glufosfamide is a new alkylating agent in which the active metabolite of isophosphoramide mustard is covalently linked to beta-D-glucose to target the glucose transporter system and increase intracellular uptake in tumor cells. We investigated this drug in a multicenter prospective phase II trial in recurrent glioblastoma multiforme (GBM). PATIENTS AND METHODS: Eligible patients had recurrent GBM following surgery, radiotherapy and no more than one prior line of chemot...

  4. The use of erythropoiesis-stimulating agents with ruxolitinib in patients with myelofibrosis in COMFORT-II: an open-label, phase 3 study assessing efficacy and safety of ruxolitinib versus best available therapy in the treatment of myelofibrosis

    OpenAIRE

    McMullin, Mary Frances; Harrison, Claire N; Niederwieser, Dietger; Demuynck, Hilde; Jäkel, Nadja; Gopalakrishna, Prashanth; McQuitty, Mari; Stalbovskaya, Viktoriya; Recher, Christian; Theunissen, Koen; Gisslinger, Heinz; Kiladjian, Jean-Jacques; Al-Ali, Haifa-Kathrin

    2015-01-01

    BACKGROUND: Anemia is considered a negative prognostic risk factor for survival in patients with myelofibrosis. Most patients with myelofibrosis are anemic, and 35-54 % present with anemia at diagnosis. Ruxolitinib, a potent inhibitor of Janus kinase (JAK) 1 and JAK2, was associated with an overall survival benefit and improvements in splenomegaly and patient-reported outcomes in patients with myelofibrosis in the two phase 3 COMFORT studies. Consistent with the ruxolitinib mechanism of actio...

  5. 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

  6. Design and rationale of FOCUS (PX-171-011): A randomized, open-label, phase 3 study of carfilzomib versus best supportive care regimen in patients with relapsed and refractory multiple myeloma (R/R MM)

    International Nuclear Information System (INIS)

    Carfilzomib is a next-generation proteasome inhibitor with single-agent activity in patients with relapsed and refractory multiple myeloma (R/R MM). In PX-171-003-A1, a single-arm phase 2 study of carfilzomib monotherapy in heavily pretreated patients, the overall response rate was 23.7%, 37% of patients achieved ≥ minimal response and median overall survival (OS) was 15.6 months. Based on this study, carfilzomib was recently approved by the US Food and Drug Administration for the treatment of R/R MM. Herein we describe the trial design and rationale for a phase 3 randomized study, FOCUS (CarFilzOmib for AdvanCed Refractory MUltiple Myeloma European Study), being conducted to compare OS after treatment with single-agent carfilzomib to best supportive care (BSC) regimen in R/R MM. Patients must have received ≥3 prior regimens, must be responsive to at least 1 line of therapy, and be refractory to their most recent therapy. Eligible patients are randomized 1:1 to receive either carfilzomib (28-day cycles at 20 mg/m2 IV on Days 1–2 of Cycle 1, escalating to 27 mg/m2 IV on Days 8, 9, 15, and 16 and continuing at 27 mg/m2 through Cycle 9 and Days 1, 2, 15, and 16 ≥ Cycle 10) or an active BSC regimen (corticosteroid treatment of prednisolone 30 mg, dexamethasone 6 mg, or equivalent every other day with optional cyclophosphamide 50 mg PO once daily). Patients will continue treatment until disease progression, unacceptable toxicity, or treatment discontinuation and will then enter long-term follow-up for survival. The primary endpoint is OS and secondary endpoints include progression-free survival, overall response rate, and safety. Disease assessments will be determined according to the International Myeloma Working Group Uniform Response Criteria with minimal response per European Blood and Marrow Transplantation Group criteria. This phase 3 trial will provide more rigorous data for carfilzomib, as this is the first carfilzomib study with OS as the primary

  7. 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.

  8. An Open-Label, Single-Arm, Phase 2 Trial of the Polo-Like Kinase Inhibitor Volasertib (BI 6727) in Patients With Locally Advanced or Metastatic Urothelial Cancer

    Science.gov (United States)

    Stadler, Walter M.; Vaughn, David J.; Sonpavde, Guru; Vogelzang, Nicholas J.; Tagawa, Scott T.; Petrylak, Daniel P.; Rosen, Peter; Lin, Chia-Chi; Mahoney, John; Modi, Sanjiv; Lee, Peter; Ernstoff, Marc S.; Su, Wu-Chou; Spira, Alexander; Pilz, Korinna; Vinisko, Richard; Schloss, Charles; Fritsch, Holger; Zhao, Charles; Carducci, Michael A.

    2015-01-01

    BACKGROUND Polo-like kinases (Plks) control multiple steps during the cell cycle, and Plk1 is overexpressed in urothelial cancer (UC). Volasertib (BI 6727), a Plk inhibitor, has demonstrated antitumor activity in several malignancies, including UC. In this phase 2 trial, the authors investigated volasertib as a second-line treatment in advanced/metastatic UC. METHODS Patients who progressed within 2 years of 1 prior chemotherapy regimen received 300 mg volasertib on day 1 every 3 weeks. The dose was escalated to 350 mg in cycle 2 if volasertib was tolerated in cycle 1. The primary endpoint was tumor response, which was assessed every 6 weeks; secondary endpoints were progression-free survival, overall survival, duration of response, safety, and pharmacokinetics. RESULTS Fifty patients were enrolled, and the median patient age was 68.5 years (range, 52-83 years). All patients had received prior platinum, 94% of patients had relapsed ≤2 years after prior therapy, 36% had liver metastases, and 54% had lung metastases. The median number of treatment cycles was 2 (range, 1-27 treatment cycles), and 23 patients were dose escalated at cycle 2. Seven patients (14%) had a partial response, 13 (26%) had stable disease, and 30 (60%) progressed within 6 weeks. The median response duration was 41 weeks (range, 29.1-77.3 weeks). The median progression-free survival was 1.4 months, and the median overall survival was 8.5 months. The most frequent grade 3 and 4 adverse events were neutropenia (28%), thrombocytopenia (20%), and anemia (16%). No cumulative toxicity was observed. CONCLUSIONS Volasertib as second-line treatment for advanced/metastatic UC had an acceptable safety profile but demonstrated insufficient antitumor activity for further evaluation as a monotherapy. PMID:24339028

  9. Analgesic and thermic responses to intravenously administered morphine in 8- and 24-week-old rats.

    Science.gov (United States)

    Bhargava, H N; Villar, V M

    1991-01-01

    The analgesic and thermic responses to morphine (5 and 10 mg/kg) injected intravenously to 8- and 24-week-old male Sprague-Dawley rats were determined. Greater analgesic and lower hyperthermic responses to morphine in 24-week-old rats in comparison to 8-week-old rats were observed. The pharmacokinetic parameters of morphine administered intravenously were also determined. Cmax for 5 and 10 mg/kg doses of morphine were smaller in 24-week-old rats in comparison to 8-week-old rats; however, AUC0----infinity was smaller only for 5 mg/kg dose. For 10 mg/kg dose, mean residence time (MRT) and the apparent steady state volume of distribution (Vss) for the older rats were higher than for the younger ones, but for 5 mg/kg dose the values did not differ. The enhanced responses to morphine in older age group of rats for 5 mg/kg dose cannot be explained solely on the basis of pharmacokinetics. However, for 10 mg/kg dose of morphine, the greater responses in 24-week-old rats could probably be related to increases in MRT and Vss. Factors other than serum kinetics, like kinetics of morphine in the brain as well as the brain opiate receptors, may also be involved in the differential effects of morphine in rats of different ages. PMID:1784625

  10. Temporal organization of fetal behavior from 24-weeks gestation onwards in normal and complicated pregnancies

    NARCIS (Netherlands)

    Nijhuis, IJM; ten Hof, J; Nijhuis, JG; Mulder, EJH; Narayan, H; Taylor, DJ; Visser, GHA

    1999-01-01

    Developmental aspects of behavioral organization were investigated in 29 healthy fetuses from 24-weeks gestation onwards: (a) short-term association between body (GM) and eye (EM) movements; (b) linkage of pairs of the three state variables [fetal heart rate pattern (FHRP), GM, and EM]; and (c) sequ

  11. Round ligament lipoma mimicking acute appendicitis in a 24-week pregnant female: a case report.

    Science.gov (United States)

    Miller, T J; Paulk, D G

    2013-04-01

    An exhaustive search of the literature using the Pub Med database revealed no reports of round ligament lipomas mimicking acute appendicitis in pregnant patients. There are relatively few articles on round ligament lipomas and even less on round ligament lipomas during pregnancy. This case report is on a 27-year-old 24-week pregnant female who presented with signs and symptoms similar to acute appendicitis who in fact had a large right pelvic round ligament lipoma that was causing her pain.

  12. Diacerein for osteoarthritis: An open-label comparative trial

    Directory of Open Access Journals (Sweden)

    L. V. Luchikhina

    2016-01-01

    Full Text Available Osteoarthritis (OA is a degenerative joint disease that is accompanied by cartilage destruction, synovial membrane inflammatory changes, and subchondral bone remodeling.Objective: to perform comparative evaluation of the efficiency of knee OA treatment with diacerein, hyaluronic acid, and nonsteroidal antiinflammatory drugs at short- and long-term follow-up.Patients and methods. An open-label comparative enrolled 192 patients with knee arthritis: 68.5% women and 31.5% men (mean age, 52.7±1.79 years; mean disease duration, 7 years. The patients were divided into three groups matched for gender, age, and disease duration: Group 1 (n=63 took diacerein 100 mg/day; Group 2 (n=65 received intraarticular hyaluronic acid 2 ml thrice at an interval of 7 days; Group 3 (n=64 had diclofenac 75 mg/day. The patients of all the three groups had a similar magnitude of its symptoms and Kellgren grade. Magnetic resonance imaging (MRI and arthroscopic examination of the knee joint were performed to assess the results of treatment in the patients.Results. To evaluate the chondroprotective effect of the drugs, the authors used their proposed arthroscopic and MRI criteria (sensitivity, 89.7%; specificity, 93.1% that allow abnormally changed and normal cartilages to be identified. At months 2 of treatment, all the three drugs ensured a considerable pain intensity reduction that persisted till 12 weeks. The important benefit of diacerein and hyaluronic acid was their aftereffect for further 3 months.

  13. A perspective,open-label,and multi-center phase Ⅱ study of FOLFOX 4 regimen as systemic therapy for patients with unresectable hepatocellular carcinoma%FOLFOX4方案治疗晚期肝细胞癌的多中心Ⅱ期临床研究

    Institute of Scientific and Technical Information of China (English)

    龚新雷; 秦叔逵; 王雅杰; 邢宝才; 吴晴; 曹梦苒; 华海清; 刘秀峰

    2011-01-01

    目的:在初步观察的基础上,探讨以奥沙利铂(OXA)和亚叶酸钙/5-氟尿嘧啶(LV/5-FU)组成的FOLFOX 4方案进行系统化疗,治疗无法手术切除的国人晚期肝细胞癌(HCC)患者的有效性和安全性.方法:前瞻性、单臂、开放性、多中心的Ⅱ期临床研究,采取Simon二阶段法.经病理组织学和/或细胞学检查确诊的局部晚期、无法手术或已有远处转移的HCC患者,给予FOLFOX 4方案进行全身化疗,即 OXA 85 Mg*m(-2),静滴,d1;LV200mg·m(-2),静滴2h,d1,d2;5-FU400mg·m(-2),静推,继以600 mg·m(-2),持续静脉滴注22 h,d1,d2;每2周重复;直至疾病进展或最多不超过6个周期.每2个周期(6周时间)按照RECIST标准(1.0版)评价客观疗效,观察至疾病进展时间(TTP)和生存期(OS),并动态监测血清甲胎蛋白(AFP)的变化.一般毒性,按照NCI-CTC 2.0版标准观察和判定;神经系统毒性,参照OXA专用神经病变分级标准评判.结果:4家肿瘤中心参加,共入组25例患者,其中22例可以评估疗效,结果获得完全缓解(CR)1例,部分缓解(PR)3例,稳定(SD)7例,进展11例,客观缓解率(CR + PR)为18.2%,疾病控制率(DCR = CR +PR + SD)为50.0%;中位,TTP为2.0个月(95%可信区间:1.3~4.0个月),中位OS为12.4个月.AFP反应率为28%.常见的毒性反应为粒细胞减少和轻度的周围神经毒性.结论:以奥沙利铂为主的FOLFOX 4方案进行系统化疗,对于国人晚期肝细胞癌具有良好的客观疗效和一定的生存获益,不良反应较轻,患者易于耐受,值得进一步开展大规模、随机对照的Ⅲ期临床研究.%Objective: To observe the efficacy and safety of oxaliplatin (OXA) combined with LV/5-FU ( FOLFOX 4 regimen ) in Chinese patients with unresectable hepatocellular carcinoma ( HCC ). Methods: It was a perspective, open-label, single arm, and multi-center phase II study, conducted in 4 cancer centers in China. The patients had pathologically confirmed as inoperable HCC with or without

  14. 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

  15. Open-Label Treatment With Citalopram in Patients With Irritable Bowel Syndrome: A Pilot Study

    OpenAIRE

    Masand, Prakash S.; Gupta, Sanjay; Schwartz, Thomas L; Virk, Subhdeep; Hameed, Ahmad; Kaplan, David S.

    2005-01-01

    Background: This open-label pilot study investigated whether the selective serotonin reuptake inhibitor (SSRI) citalopram improves symptoms of irritable bowel syndrome (IBS), a functional gastrointestinal disorder with frequent psychiatric comorbidity.

  16. A clinical study on ultrasonographic measurement of cervical length at 18-24 weeks of gestation and pregnancy outcome

    Directory of Open Access Journals (Sweden)

    Jayati Nath

    2016-04-01

    Conclusions: Shorter cervices lead to shorter gestations and early labour. Thus ultrasonographic measurement of cervical length at 18-24 weeks of gestation is very important, more so in asymptomatic women and can be utilized as a tool for predicting adverse pregnancy outcome especially preterm labour and delivery. [Int J Reprod Contracept Obstet Gynecol 2016; 5(4.000: 1088-1092

  17. 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

  18. 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

  19. 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…

  20. Open-label adjunctive zonisamide in the treatment of bipolar disorders: A prospective trial

    NARCIS (Netherlands)

    McElroy, S.L.; Suppes, T.; Keck, P.E.; Black, D.; Frye, M.A.; Altshuler, L.L.; Nolen, W.A.; Kupka, R.W.; Leverich, G.S.; Walden, J.; Grunze, H.; Post, R.M.

    2005-01-01

    Background: The response of 62 outpatients with DSM-IV bipolar disorders to open-label adjunctive zonisamide was evaluated in a prospective 8-week acute trial, followed by a 48-week continuation trial, conducted from June 2001 through May 2002. Method: During the acute trial, response to zonisamide

  1. Open-label adjunctive zonisamide in the treatment of bipolar disorders : A prospective trial

    NARCIS (Netherlands)

    McElroy, SL; Suppes, T; Keck, PE; Frye, MA; Altshuler, LL; Nolen, WA; Kupka, RW; Leverich, GS; Walden, J; Grunze, H; Post, RM; Black, D.

    2005-01-01

    Background: The response of 62 outpatients with DSM-IV bipolar disorders to open-label adjunctive zonisamide was evaluated in a prospective 8-week acute trial, followed by a 48-week continuation trial, conducted from June 2001 through May 2002. Method: During the acute trial, response to zonisamide

  2. 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…

  3. 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

  4. Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial.

    Science.gov (United States)

    Kosaka, H; Okamoto, Y; Munesue, T; Yamasue, H; Inohara, K; Fujioka, T; Anme, T; Orisaka, M; Ishitobi, M; Jung, M; Fujisawa, T X; Tanaka, S; Arai, S; Asano, M; Saito, D N; Sadato, N; Tomoda, A; Omori, M; Sato, M; Okazawa, H; Higashida, H; Wada, Y

    2016-01-01

    Recent studies have suggested that long-term oxytocin administration can alleviate the symptoms of autism spectrum disorder (ASD); however, factors influencing its efficacy are still unclear. We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy. This trial consisted of double-blind (12 weeks), open-label (12 weeks) and follow-up phases (8 weeks). To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase. Next, we measured single-nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR). In the intention-to-treat population, no outcomes were improved after oxytocin administration. However, in male participants, Clinical Global Impression-Improvement (CGI-I) scores in the high-dose group, but not the low-dose group, were significantly higher than in the placebo group. Furthermore, we examined whether oxytocin efficacy, reflected in the CGI-I scores, is influenced by estimated daily dosage and OXTR polymorphisms in male participants. We found that >21 IU per day oxytocin was more effective than ⩽21 IU per day, and that a SNP in OXTR (rs6791619) predicted CGI-I scores for ⩽21 IU per day oxytocin treatment. No severe adverse events occurred. These results suggest that efficacy of long-term oxytocin administration in young men with high-functioning ASD depends on the oxytocin dosage and genetic background of the oxytocin receptor, which contributes to the effectiveness of oxytocin treatment of ASD. PMID:27552585

  5. STX209 (Arbaclofen) for Autism Spectrum Disorders: An 8-Week Open-Label Study

    OpenAIRE

    Erickson, Craig A.; Veenstra-Vanderweele, Jeremy M.; Melmed, Raun D.; McCracken, James T.; Ginsberg, Lawrence D.; Sikich, Linmarie; Scahill, Lawrence; Cherubini, Maryann; Zarevics, Peter; Walton-Bowen, Karen; Carpenter, Randall L.; Wang, Paul P.; King, Bryan H.; Bear, Mark

    2013-01-01

    STX209 (arbaclofen), a selective GABA-B agonist, is hypothesized to modulate the balance of excitatory to inhibitory neurotransmission, and has shown preliminary evidence of benefit in fragile X syndrome. We evaluated its safety, tolerability, and efficacy in non-syndromic autism spectrum disorders, in an 8-week open-label trial enrolling 32 children and adolescents with either Autistic Disorder or Pervasive Developmental Disorder—Not Otherwise Specified, and a score ≥17 on the Aberrant Behav...

  6. Escitalopram in obsessive-compulsive disorder: a randomized, placebo-controlled, paroxetine-referenced, fixed-dose, 24-week study

    DEFF Research Database (Denmark)

    Stein, Dan J; Andersen, Elisabeth Anne Wreford; Tonnoir, Brigitte;

    2007-01-01

    OBJECTIVE: A randomized, placebo controlled fixed-dose trial was undertaken to determine the efficacy and tolerability of escitalopram in obsessive-compulsive disorder (OCD), using paroxetine as the active reference. RESEARCH DESIGN AND METHODS: A total of 466 adults with OCD from specialized...... clinical centres, psychiatric hospital departments, psychiatric practices, or general practice were randomized to one of four treatment groups: escitalopram 10 mg/day (n = 116), escitalopram 20 mg/day (n = 116), paroxetine 40 mg/day (n = 119), or placebo (n = 115) for 24 weeks. The primary efficacy...... of adverse events, and on changes in vital signs (blood pressure and pulse). Main outcome measures; RESULTS: Escitalopram 20 mg/day was superior to placebo on the primary and all secondary outcome endpoints, including remission. Escitalopram 10 mg/day and paroxetine 40 mg/day were also effective on...

  7. Metabolic effects of a 24-week energy-restricted intervention combined with low or high dairy intake in overweight women

    DEFF Research Database (Denmark)

    Zheng, Hong; Lorenzen, Janne Kunchel; Astrup, Arne;

    2016-01-01

    We investigated the effect of a 24-week energy-restricted intervention with low or high dairy intake (LD or HD) on the metabolic profiles of urine, blood and feces in overweight/obese women by NMR spectroscopy combined with ANOVA-simultaneous component analysis (ASCA). A significant effect of dairy...... intake was found on the urine metabolome. HD intake increased urinary citrate, creatinine and urea excretion, and decreased urinary excretion of trimethylamine-N-oxide (TMAO) and hippurate relative to the LD intake, suggesting that HD intake was associated with alterations in protein catabolism, energy...... metabolism and gut microbial activity. In addition, a significant time effect on the blood metabolome was attributed to a decrease in blood lipid and lipoprotein levels due to the energy restriction. For the fecal metabolome, a trend for a diet effect was found and a series of metabolites, such as acetate...

  8. Effect of 24-week repeated short-time walking based training program on physical fitness of black Cameroonian obese women.

    Science.gov (United States)

    Guessogo, Wiliam R; Temfemo, Abdou; Mandengue, Samuel H; Assomo Ndemba, Peguy B; Messina Ondoua, Regine T; Hamadou, André; Etoundi-Ngoa, Laurent S; Ahmaidi, Said

    2016-04-01

    This study aimed to examine the effects of a training program based on repetition of short-time walk sequences on cardiorespiratory response, physical performance and metabolic parameters in black Cameroonian obese women. One hundred thirty-nine obese women (body mass in-dex [BMI]>30 kg/m2) were divided into three groups: premenopausal (Pre-M; 39.7±7.9 yr; n=48), postmenopausal (Post-M; 55.0±2.5 yr; n=61) and control group (CONT; 48.7±9.4 yr; n=30). Only Pre-M and Post-M completed 24-week repeated short-time walking program. An-thropometric, cardiorespiratory, metabolic parameters, and the 6-min walk distance (6MWD) were measured at baseline (S1), 12 weeks follow-up (S2), and 2 days after the last session (S3). Significant changes were observed in weight, BMI, fatty mass and 6MWD in Pre-M and Post-M after 24 weeks. The waist and hip circumferences, percentages of water, muscle mass and bone mass changed in Post-M. Total cholesterol, triglycerides, low density lipoprotein and forced expiratory volumes in 1 and 6 sec showed significant improvements in Pre-M and Post-M. High density lipoprotein increased only in Post-M (0.5±0.2 g/L vs 0.7±0.1 g/L, P=0.041). In conclusion, this training modality could constitute an option for obese women rehabilitation. PMID:27162770

  9. Prediction of prolonged pregnancy in nulliparous women by transvaginal ultrasonographic measurement of cervical length at 20-24 weeks and 37 weeks.

    Science.gov (United States)

    Suh, Young Hoon; Park, Kyo Hoon; Hong, Joon-Seok; Noh, Jae Hong

    2007-02-01

    This study was done to evaluate transvaginal ultrasonographic measurement of cervical length at 20 to 24 weeks and 37 weeks as a predictor of prolonged pregnancy (defined as a pregnancy that extended beyond 41+2 weeks of gestation [289 days]) in nulliparous women. This prospective observational study enrolled 149 consecutive nulliparous women with singleton gestation at 37 weeks. Cervical length was measured by transvaginal ultrasonography at 20 to 24 weeks and 37 weeks. Cervical length at 37 weeks, but not at 20 to 24 weeks, was significantly longer in women delivered at >41+2 weeks than in those delivered at prolonged pregnancy was 30 mm, with a sensitivity of 78% and a specificity of 62%. Cervical length assessed by transvaginal ultrasonography at 37 weeks can predict the likelihood of prolonged pregnancy in nulliparous women. However, there is no association between cervical length at 20 to 24 weeks and the occurrence of prolonged pregnancy.

  10. Antiretroviral pharmacokinetics in mothers and breastfeeding infants from 6 to 24 weeks post partum: results of the BAN Study

    Science.gov (United States)

    Corbett, Amanda H; Kayira, Dumbani; White, Nicole R; Davis, Nicole L; Kourtis, Athena P; Chasela, Charles; Martinson, Francis; Phiri, Grace; Musisi, Bonaface; Kamwendo, Deborah; Hudgens, Michael G; Hosseinipour, Mina C; Nelson, Julie AE; Ellington, Sascha R; Jamieson, Denise J; van der Horst, Charles; Kashuba, Angela

    2014-01-01

    Background An intensive, prospective, open-label pharmacokinetic (PK) study in a subset of HIV-infected mothers and their uninfected infants enrolled in the Breastfeeding, Antiretroviral, and Nutrition study was performed to describe drug exposure and antiviral response. Methods Women using Combivir®[zidovudine (ZDV)+ lamivudine (3TC)]+Aluvia®[lopinavir/ritonavir(LPV/RTV)] were enrolled. Breast milk (BM) and mother and infant plasma (MP, IP) samples were obtained over 6hrs after observed dosing at 6, 12, or 24wks post-partum for drug concentrations and HIV RNA. Results 30 mother/infant pairs (10 each at 6, 12,and 24wks post-partum) were enrolled. Relative to MP, BM concentrations of ZDV and 3TC were 35% and 21% higher, while LPV and RTV were 80% lower. Only 3TC was detected in IP with concentrations 96% and 98% lower than MP and BM, respectively. Concentrations in all matrices were similar at 6-24wks. The majority (98.3%) of BM concentrations were >HIVwt IC50, with one having detectable virus. There was no association between PK parameters and MP or BM HIV RNA. Conclusions ZDV and 3TC concentrated in BM while LPV and RTV did not, possibly due to protein binding and drug transporter affinity. Undetectable to low ARV concentrations in IP suggests prevention of transmission while breast feeding may be due to ARV effects on systemic or BM HIV RNA in the mother. Low IP 3TC exposure may predispose an infected infant to HIV resistance, necessitating testing and treating infants early. PMID:24464632

  11. 24-weeks Pilates-aerobic and educative training to improve body fat mass in elderly Serbian women

    Directory of Open Access Journals (Sweden)

    Ruiz-Montero PJ

    2014-01-01

    Full Text Available Pedro Jesús Ruiz-Montero,1 Alfonso Castillo-Rodriguez,2 Milena Mikalacki,3 Čokorilo Nebojsa,3 Darinka Korovljev3 1Department of Physical Education and Sport, Faculty of Physical Activity and Sport, University of Granada, Granada, Spain; 2Faculty of Sport, University of Pablo de Olavide, Seville, Spain; 3Faculty of Sport and Physical Education, University of Novi Sad, Novi Sad, Serbia Background: The purpose of this study was to examine the differences in anthropometric measurements using an aerobic and Pilates exercise program which lasted 24 weeks. Method: This was a clinical intervention study of 303 women over the age of 60 living in Novi Sad, Serbia. Changes in body mass index and skinfold thickness were estimated through height, weight, and anthropometric measurements. The program comprised Pilates exercises for upper- and lower-body strength, agility, and aerobic capacity. Results: Fat mass (FM improved significantly (pre-test, 32.89%, 8.65; post-test, 28.25%, 6.58; P<0.01. Bone diameters and muscle perimeters showed no significant changes pre- and post-test (P>0.05, but there was a higher correlation between FM (% and waist–hip ratio (rho, 0.80; P<0.01. Conclusion: A mixed program of aerobics and Pilates, controls and improves baseline muscle mass and decreases FM values, without causing deterioration during practice and follow-up exercises. Keywords: lean body mass, anthropometric measures, educative program

  12. 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.......025). CONCLUSION: In dcSSc infliximab did not show clear benefit at 26 weeks but was associated with clinical stabilisation and a fall in two laboratory markers of collagen synthesis. The frequency of suspected infusion reactions may warrant additional immunosuppression in any future studies in systemic sclerosis....

  13. Efficacy, safety and tolerability of escitalopram in doses up to 50 mg in Major Depressive Disorder (MDD: an open-label, pilot study

    Directory of Open Access Journals (Sweden)

    Crawford Gordon M

    2011-03-01

    Full Text Available Abstract Background Escitalopram is licensed for use at doses up to 20 mg but is used clinically at higher doses. There is limited published data at higher doses and none in the treatment of Major Depressive Disorder (MDD. Methods This open-label, pilot study was designed to investigate the efficacy, safety and tolerability of escitalopram in doses up to 50 mg in MDD. It was conducted in 60 primary care patients with MDD who had not responded to adequate treatment with citalopram. Patients were treated with escalating doses of escitalopram up to 50 mg for up to 32 weeks until they achieved remission (Montgomery-Asberg Depression Rating Scale [MADRS] ≤8 or failed to tolerate the dose. Results Forty-two patients (70% completed the study. Twenty-one patients (35% achieved remission with 8 of the 21 patients (38% needing the 50 mg dose to achieve remission. Median time to remission was 24 weeks and median dose in remission was 30 mg. No significant safety issues were identified although tolerability appeared to decline above a dose of 40 mg with 26% of patients unable to tolerate 50 mg. Twelve (20% patients had adverse events leading to discontinuation. The most common adverse events were headache (35%, nausea, diarrhoea and nasopharyngitis (all 25%. Minor mean weight gain was found during the study, which did not appear to be dose-related. Half of the patients who completed the study chose to continue treatment with escitalopram rather than taper down the dose at 32 weeks. Conclusions Dose escalation with escitalopram above 20 mg may have a useful role in the management of patients with MDD, although further studies are needed to confirm this finding. Trial Registration ClinicalTrials.gov: NCT00785434

  14. Comparative study of amrutbhallataka and glucosamine sulphate in osteoarthritis: Six months open label randomized controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Ashwinikumar Raut

    2013-01-01

    Full Text Available Background: AmrutBhallatak (ABFN02, a ′rasayana′ drug from Ayurveda is indicated in degenerative diseases and arthritis. Objective: To evaluate safety and efficacy of ABFN02 in osteoarthritis (OA and compare it with Glucosamine sulphate (GS Materials and Methods: This was a r andomized open comparative study. Ambulant OPD patients of OA knees (n = 112 were enrolled for 24 weeks. Tablets (750mg each of GS and ABFN02 were matched. Three groups of patients: (A GS, one tablet × twice/day × 24 weeks. (B ABFN02, incremental pulse dosage (one tablet x twice/day × two weeks, two tablets × twice/day × two weeks, three tablets × twice/day × two weeks, two such cycles of drug and non-drug phases alternately for six weeks each (C ABFN02 continuous dosage akin to GS. Pain visual analogue score (Pain-VAS and Western Ontario and Mc-Master University Osteoarthritis Index (WOMAC were the primary outcome measures. Secondary outcome measures were Health assessment questionnaire (HAQ, paracetamol consumption, 50 feet walking, physician and patient global assessment, knee stiffness, knee status, urinary CTX II, serum TNFa-SRI, SRII and MRI knee in randomly selected patients. Results: ABFNO2 and GS demonstrated, adherence to treatment 87.75% and 74.3%, reduction in Pain-VAS at rest 61.05% and 57.1%, reduction in pain-VAS on activity 57.4% and 59.8%, WOMAC score drop 62.8% and 59.1% respectively. Secondary outcome measures were comparable in all groups. Safety measures were also comparable. No serious adverse events reported. However, asymptomatic reversible rise in liver enzymes was noted in the ABFNO2 group. Conclusions: ABFN02 has significant activity in OA; the formulation needs further investigation.

  15. Single-dose pharmacokinetics of 2 or 3 tablets of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen (MNK-155) under fed and fasted conditions: two randomized open-label trials

    OpenAIRE

    Devarakonda, Krishna; Kostenbader, Kenneth; Giuliani, Michael J.; Young, Jim L.

    2015-01-01

    Background Biphasic immediate-release (IR)/extended-release (ER) hydrocodone bitartrate (HB)/acetaminophen (APAP) 7.5/325-mg tablets are formulated with gastroretentive ER drug delivery technology that has been associated with clinically meaningful food effects in other approved products. Two phase 1 studies evaluated potential effects of food on single-dose pharmacokinetics of IR/ER HB/APAP tablets. Methods These were single-center, open-label, randomized, single-dose, 3-period crossover stu...

  16. Fluticasone/formoterol combination therapy is as effective as fluticasone/salmeterol in the treatment of asthma, but has a more rapid onset of action: an open-label, randomized study

    OpenAIRE

    McAulay Kirsten; Dymek Andrzej; Bodzenta-Lukaszyk Anna; Mansikka Heikki

    2011-01-01

    Abstract Background The inhaled corticosteroid (ICS) fluticasone propionate (fluticasone) and the long-acting β2-agonist (LABA) formoterol fumarate (formoterol) are being made available as a combination product (fluticasone/formoterol, flutiform®) in a single aerosol inhaler. This 12-week, open-label, randomized, active-controlled, parallel-group, multicentre, phase 3 study compared the efficacy and safety of fluticasone/formoterol with the commercially available combination product fluticaso...

  17. An enhanced postnatal autoimmune profile in 24 week-old C57BL/6 mice developmentally exposed to TCDD

    International Nuclear Information System (INIS)

    Developmental exposure of mice to the environmental contaminant and AhR agonist, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), causes persistent postnatal suppression of T cell-mediated immune responses. The extent to which prenatal TCDD may induce or exacerbate postnatal autoimmune disease remains unknown. In the present study, time-pregnant high affinity AhR C57BL/6 mice received a single oral administration of 0, 2.5, or 5 μg/kg TCDD on gestation day (gd) 12. Offspring of these mice (n = 5/gender/treatment) were evaluated at 24 weeks-of-age and showed considerable immune dysregulation that was often gender-specific. Decreased thymic weight and percentages of CD4+CD8+ thymocytes, and increased CD4+CD8- thymocytes, were present in the female but not male offspring. Males but not females showed decreased CD4-CD8+ T cells, and increased Vβ3+ and Vβ17a+ T cells, in the spleen. Males but not females also showed increased percentages of bone marrow CD24-B220+ B cell progenitors. Antibody titers to dsDNA, ssDNA and cardiolipin displayed increasing trends in both male and female mice, reaching significance for anti-dsDNA in both genders and for ssDNA in males at 5 μg/kg TCDD. Immunofluorescent staining of IgG and C3 deposition in kidney glomeruli increased in both genders of prenatal TCDD-exposed mice, suggestive of early stages of autoimmune glomerulonephritis. Collectively, these results show that exposure to TCDD during immune system development causes persistent humoral immune dysregulation as well as altered cell-mediated responses, and induces an adult profile of changes suggestive of increased risk for autoimmune disease

  18. 24-weeks Pilates-aerobic and educative training to improve body fat mass in elderly Serbian women

    Directory of Open Access Journals (Sweden)

    Ruiz-Montero PJ

    2014-01-01

    Full Text Available Pedro Jesús Ruiz-Montero,1 Alfonso Castillo-Rodriguez,2 Milena Mikalacki,3 Čokorilo Nebojsa,3 Darinka Korovljev31Department of Physical Education and Sport, Faculty of Physical Activity and Sport, University of Granada, Granada, Spain; 2Faculty of Sport, University of Pablo de Olavide, Seville, Spain; 3Faculty of Sport and Physical Education, University of Novi Sad, Novi Sad, SerbiaBackground: The purpose of this study was to examine the differences in anthropometric measurements using an aerobic and Pilates exercise program which lasted 24 weeks.Method: This was a clinical intervention study of 303 women over the age of 60 living in Novi Sad, Serbia. Changes in body mass index and skinfold thickness were estimated through height, weight, and anthropometric measurements. The program comprised Pilates exercises for upper- and lower-body strength, agility, and aerobic capacity.Results: Fat mass (FM improved significantly (pre-test, 32.89%, 8.65; post-test, 28.25%, 6.58; P<0.01. Bone diameters and muscle perimeters showed no significant changes pre- and post-test (P>0.05, but there was a higher correlation between FM (% and waist–hip ratio (rho, 0.80; P<0.01.Conclusion: A mixed program of aerobics and Pilates, controls and improves baseline muscle mass and decreases FM values, without causing deterioration during practice and follow-up exercises.Keywords: lean body mass, anthropometric measures, educative programA Letter to the Editor has been received and published for this article.

  19. 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...

  20. Open-label add-on treatment trial of minocycline in fragile X syndrome

    Directory of Open Access Journals (Sweden)

    Tranfaglia Michael

    2010-10-01

    Full Text Available Abstract Background Fragile X syndrome (FXS is a disorder characterized by a variety of disabilities, including cognitive deficits, attention-deficit/hyperactivity disorder, autism, and other socio-emotional problems. It is hypothesized that the absence of the fragile X mental retardation protein (FMRP leads to higher levels of matrix metallo-proteinase-9 activity (MMP-9 in the brain. Minocycline inhibits MMP-9 activity, and alleviates behavioural and synapse abnormalities in fmr1 knockout mice, an established model for FXS. This open-label add-on pilot trial was conducted to evaluate safety and efficacy of minocycline in treating behavioural abnormalities that occur in humans with FXS. Methods Twenty individuals with FXS, ages 13-32, were randomly assigned to receive 100 mg or 200 mg of minocycline daily. Behavioural evaluations were made prior to treatment (baseline and again 8 weeks after daily minocycline treatment. The primary outcome measure was the Aberrant Behaviour Checklist-Community Edition (ABC-C Irritability Subscale, and the secondary outcome measures were the other ABC-C subscales, clinical global improvement scale (CGI, and the visual analog scale for behaviour (VAS. Side effects were assessed using an adverse events checklist, a complete blood count (CBC, hepatic and renal function tests, and antinuclear antibody screen (ANA, done at baseline and at 8 weeks. Results The ABC-C Irritability Subscale scores showed significant improvement (p Conclusions Results from this study demonstrate that minocycline provides significant functional benefits to FXS patients and that it is well-tolerated. These findings are consistent with the fmr1 knockout mouse model results, suggesting that minocycline modifies underlying neural defects that account for behavioural abnormalities. A placebo-controlled trial of minocycline in FXS is warranted. Trial registration ClinicalTrials.gov Open-Label Trial NCT00858689.

  1. 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

  2. Six-Week Open-Label Reboxetine Treatment in Children and Adolescents with Attention-Deficit/hyperactivity Disorder.

    Science.gov (United States)

    Ratner, Sharon; Laor, Nathaniel; Bronstein, Yifat; Weizman, Abraham; Toren, Paz

    2005-01-01

    Objective: This open-label study assessed the effectiveness of reboxetine, a selective norepinephrine reuptake inhibitor, in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) resistant to a previous methylphenidate trial. Method: Thirty-one child and adolescent outpatients, aged 8 to 18 (mean age, 11.7; SD = 2.87)…

  3. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Computerized cognitive remediation training for schizophrenia: an open label, multi-site, multinational methodology study.

    Science.gov (United States)

    Murthy, N V; Mahncke, H; Wexler, B E; Maruff, P; Inamdar, A; Zucchetto, M; Lund, J; Shabbir, S; Shergill, S; Keshavan, M; Kapur, S; Laruelle, M; Alexander, R

    2012-08-01

    A recent single-site study (Fisher et al., 2009. Am J Psychiatry. 166 (7) 805-11) showed that repeated training with the Brain Fitness Program (BFP) improved performance on a battery of neuropsychological tasks. If replicated these data suggest an important non-pharmacological method for ameliorating cognitive impairment in schizophrenia. Our study evaluated the BFP training effects in an open-label, multi-site, multinational clinical trial. Fifty-five stable adult patients with schizophrenia on regular antipsychotic medication completed ≥ 32 BFP training sessions over 8-10 weeks. Training effects on cognitive performance and functional capacity outcome measures were measured using CogState® schizophrenia battery, UCSD Performance based Skills Assessment (UPSA-2) and Cognitive Assessment Interview (CAI). BFP training showed a large and significant treatment effect on a training exercise task (auditory processing speed), however this effect did not generalize to improved performance on independent CogState® assessment. There were no significant effects on UPSA-2 or CAI scores. Our study demonstrated the feasibility of implementing BFP training in a multi-site study. However, BFP training did not show significant treatment effects on cognitive performance or functional capacity outcome measures despite showing large and significant effects on a training exercise. PMID:22342330

  6. 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.

  7. 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

  8. Maternal Music Exposure during Pregnancy Influences Neonatal Behaviour: An Open-Label Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Ravindra Arya

    2012-01-01

    Full Text Available Objective. This study evaluated the effect of antenatal music exposure to primigravida healthy mothers on the behaviour of their term appropriate-for-date newborns assessed using Brazelton Neonatal Behavioral Assessment Scale (BNBAS. Methods. This was a single-centre, randomized, open-label controlled trial. Primigravida mothers aged 19–29 years, free of chronic medical diseases or significant deafness, with singleton pregnancy, with a gestation of 20 weeks or less, were randomized to listen to a pre-recorded music cassette for approximately 1 hour/day in addition to standard antenatal care (intervention arm or standard care only (control arm. Perinatal factors with adverse effect on neonatal behaviour were deemed as protocol violations. Outcome measure included scores on 7 clusters of BNBAS. Primary analysis was per protocol. The trial is registered with ClinicalTrials.gov (NCT01278329. Results. One hundred and twenty-six newborns in the music group and 134 in the control group were subjected to BNBAS assessment. The infants of mothers exposed to music during pregnancy performed significantly better on 5 of the 7 BNBAS clusters. The maximal beneficial effect was seen with respect to orientation (ES 1.13, 95% CI 0.82–1.44, <0.0001 and habituation (ES 1.05, 95% CI 0.53–1.57, =0.0001. Conclusion. Prenatal music exposure to mother significantly and favourably influences neonatal behaviour.

  9. Mirtazapine in the treatment of adolescents with major depression: an open-label, multicenter pilot study.

    Science.gov (United States)

    Haapasalo-Pesu, Kirsi-Maria; Vuola, Tapani; Lahelma, Liisa; Marttunen, Mauri

    2004-01-01

    This multicenter, open-label study with a duration of 85 days was performed to evaluate the antidepressant efficacy and safety of mirtazapine (dose range, 30-45 mg) in 12-18-year-old adolescents diagnosed with major depression. Twenty-four (24) patients (15 female patients and 9 male patients) meeting the DSM-IV criteria for major depression and the Hamilton Rating Scale for Depression (HAM-D-17) score of 18 at baseline were enrolled in the study. The primary outcome measures were HAM-D-17, Beck Depression Inventory (BDI), and Clinical Global Impression (CGI) scales. Any changes in symptoms of anxiety were measured using the Hamilton Anxiety Rating Scale (HAM-A). The average age of the 23 subjects, who were eligible for analysis, was 16.3 years (standard deviation (SD) 6.11, median 17.3). The mean daily dose of mirtazapine was 32.9 mg. Mirtazapine showed a marked efficacy on all rating scales and was well tolerated. Mirtazapine had a beneficial effect on sleep. A rapid onset of sleep and pattern of action was seen. No dropouts due to adverse events were recorded. The most common treatment-emergent adverse events were tiredness, increased appetite, and dizziness. The results of this study suggest that mirtazapine may be an effective treatment for major depression in adolescents. PMID:15319015

  10. Prospective open-label pilot trial of mirtazapine in children and adolescents with social phobia.

    Science.gov (United States)

    Mrakotsky, Christine; Masek, Bruce; Biederman, Joseph; Raches, Darcy; Hsin, Olivia; Forbes, Peter; de Moor, Carl; DeMaso, David Ray; Gonzalez-Heydrich, Joseph

    2008-01-01

    Mirtazapine is indicated for major depression and used for anxiety in adults; however, little is known about its application in pediatric populations. This is an 8-week open-label pilot study of mirtazapine in children with social phobia age 8-17 years. Primary outcomes were symptom improvement based on clinician rating and self-report, as well as tolerability based on rates of discontinuation due to adverse effects. Fifty-six percent (10/18) responded to treatment, 17% (3/18) achieved full remission. Social phobia symptoms improved significantly during the first 2 weeks of treatment, as did comorbid symptoms of depression and anxiety. Eleven patients (61%) did not complete all 8 weeks of treatment; four patients (22%) discontinued due to adverse effects including fatigue and irritability. The others discontinued due to study burden (28%), insufficient response (6%), or to pursue herbal treatment (6%). Significant weight gain was observed. Larger controlled trials are needed to further evaluate efficacy and safety. PMID:17419001

  11. 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

  12. 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.

  13. Efficacy and safety of azithromycin for uncomplicated typhoid fever: an open label non-comparative study.

    Science.gov (United States)

    Aggarwal, Anju; Ghosh, Apurba; Gomber, Sunil; Mitra, Monjori; Parikh, A O

    2011-07-01

    An open-labelled, non-comparative study was conducted in 117 children aged 2-12 years to evaluate the efficacy and safety of azithromycin (20mg/ kg/day for 6 days) for the treatment of uncomplicated typhoid fever. Of the patients enrolled based on a clinical definition of typhoid fever, 109 (93.1%) completed the study.Mean (SD) of duration of fever at presentation was 9.1(4.5) days. Clinical cure was seen in 102 (93.5%) subjects, while 7 were withdrawn from the study because of clinical deterioration. Mean day of response was 3.45±1.97. BACTEC blood culture was positive for Salmonella typhi in 17/109 (15.5%) and all achieved bacteriological cure. No serious adverse event was observed. Global well being assessed by the investigator and subjects was good in 95% cases which was done at the end of the treatment. Azithromycin was found to be safe and efficacious for the management of uncomplicated typhoid fever. PMID:21555791

  14. Maternal Music Exposure during Pregnancy Influences Neonatal Behaviour: An Open-Label Randomized Controlled Trial

    Science.gov (United States)

    Arya, Ravindra; Chansoria, Maya; Konanki, Ramesh; Tiwari, Dileep K.

    2012-01-01

    Objective. This study evaluated the effect of antenatal music exposure to primigravida healthy mothers on the behaviour of their term appropriate-for-date newborns assessed using Brazelton Neonatal Behavioral Assessment Scale (BNBAS). Methods. This was a single-centre, randomized, open-label controlled trial. Primigravida mothers aged 19–29 years, free of chronic medical diseases or significant deafness, with singleton pregnancy, with a gestation of 20 weeks or less, were randomized to listen to a pre-recorded music cassette for approximately 1 hour/day in addition to standard antenatal care (intervention arm) or standard care only (control arm). Perinatal factors with adverse effect on neonatal behaviour were deemed as protocol violations. Outcome measure included scores on 7 clusters of BNBAS. Primary analysis was per protocol. The trial is registered with ClinicalTrials.gov (NCT01278329). Results. One hundred and twenty-six newborns in the music group and 134 in the control group were subjected to BNBAS assessment. The infants of mothers exposed to music during pregnancy performed significantly better on 5 of the 7 BNBAS clusters. The maximal beneficial effect was seen with respect to orientation (ES 1.13, 95% CI 0.82–1.44, P music exposure to mother significantly and favourably influences neonatal behaviour. PMID:22518187

  15. Safety and Efficacy of Memantine in Children with Autism: Randomized, Placebo-Controlled Study and Open-Label Extension.

    OpenAIRE

    Aman, MG; Findling, RL; Hardan, AY; Hendren, RL; Melmed, RD; Kehinde-Nelson, O; Hsu, HA; Trugman, JM; Palmer, RH; Graham, SM; Gage, AT; Perhach, JL; Katz, E.

    2016-01-01

    Abnormal glutamatergic neurotransmission is implicated in the pathophysiology of autism spectrum disorder (ASD). In this study, the safety, tolerability, and efficacy of the glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist memantine (once-daily extended-release [ER]) were investigated in children with autism in a randomized, placebo-controlled, 12 week trial and a 48 week open-label extension.A total of 121 children 6-12 years of age with Diagnostic and Statistical Manual of Ment...

  16. Nilotinib (Tasigna™) in the treatment of early diffuse systemic sclerosis: an open-label, pilot clinical trial

    OpenAIRE

    Gordon, Jessica K.; Martyanov, Viktor; Magro, Cynthia; Wildman, Horatio F.; Wood, Tammara A; Huang, Wei-Ti; Crow, Mary K.; Whitfield, Michael L.; Spiera, Robert F.

    2015-01-01

    Introduction Tyrosine kinase inhibitors (TKI) are medications of interest in the treatment of Systemic Sclerosis (SSc) because of their ability to inhibit pathways involved in fibrosis. In this open-label pilot trial, our objectives were to assess the safety, efficacy, and molecular change associated with treatment of patients with diffuse cutaneous (dc)SSc with the TKI nilotinib (Tasigna™). Methods Ten adult patients with early dcSSc were treated with nilotinib. Primary endpoints were safety...

  17. Preliminary open-label clinical evaluation of the soothing and reepithelialization properties of a novel topical formulation for rosacea

    OpenAIRE

    Sparavigna A; Tenconi B; De Ponti I

    2014-01-01

    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, singl...

  18. An open-label, randomized bioavailability study with alternative methods of administration of crushed ticagrelor tablets in healthy volunteers

    OpenAIRE

    Teng, Renli; Carlson, Glenn; Hsia, Judith

    2014-01-01

    Objective: To compare the bioavailability and safety profile of crushed ticagrelor tablets suspended in water and administered orally or via nasogastric tube, with that of whole tablets administered orally. Methods: In this single-center, open-label, randomized, three-treatment crossover study, 36 healthy volunteers were randomized to receive a single 90-mg dose of ticagrelor administered orally as a whole tablet or as crushed tablets suspended in water and given orally or via a nasogastric t...

  19. Onset of bronchodilation with fluticasone/formoterol combination versus fluticasone/salmeterol in an open-label, randomized study

    OpenAIRE

    Aalbers, René; Brusselle, Guy; McIver, Tammy; Grothe, Birgit; Bodzenta-Lukaszyk, Anna

    2012-01-01

    Introduction: The inhaled corticosteroid, fluticasone propionate (fluticasone), and the long-acting beta2-agonist, formoterol fumarate (formoterol), have been combined in a single aerosol inhaler (fluticasone/formoterol). In a randomized, open-label study, fluticasone/formoterol showed similar efficacy to fluticasone/salmeterol after 12 weeks of treatment. This post-hoc analysis compared the onset of bronchodilation with the two treatments. Methods: Adults with mild-to-moderatesevere persi...

  20. Patient-reported outcomes are superior in patients with Type 2 diabetes treated with liraglutide as compared with exenatide, when added to metformin, sulphonylurea or both: results from a randomized, open-label study

    OpenAIRE

    Schmidt, W E; Christiansen, J.S.; Hammer, M; Zychma, M J; Buse, J B

    2011-01-01

    Aims The Liraglutide Effect and Action in Diabetes 6 trial was an open-label trial comparing liraglutide with exenatide as an ‘add-on’ to metformin and/or sulphonylurea. Methods Patients with Type 2 diabetes were randomized to liraglutide 1.8 mg once daily or exenatide 10 μg twice daily for 26 weeks. This was followed by a 14-week extension phase, in which all patients received liraglutide 1.8 mg once daily. Results Patient-reported outcomes were measured in 379 patients using Diabetes Treatm...

  1. The Efficacy of Neurofeedback in Patients with Major Depressive Disorder: An Open Labeled Prospective Study.

    Science.gov (United States)

    Cheon, Eun-Jin; Koo, Bon-Hoon; Choi, Joong-Hyun

    2016-03-01

    The purpose of this study was to evaluate the effect of neurofeedback on depressive symptoms and electrophysiological disturbances in patients with major depressive disorder. We recruited participants suffering from depression to evaluate efficacy of left prefrontal beta with alpha/theta training. An 8-week, prospective, open-label study was undertaken. Twenty participants were recruited. The treatment protocol was twice or three times a week training of beta at F3 with alpha/theta at Pz for 8 weeks. When every visit, patients were received beta training for 30 min, and then alpha/theta training for 30 min. Baseline, 4 and 8 week scores of; the Hamilton rating scale for Depression (HAM-D), the Hamilton rating scale for Anxiety (HAM-A), the Beck Depression Inventory (BDI)-II, the Beck Anxiety Inventory (BAI), Clinical global impression-severity (CGI-S), and pre- and post-treatment resting state EEGs were compared. Interhemispheric alpha power asymmetry (A score) was computed for homologous sites F3-F4. Pre- and post-training clinical assessments revealed significant improvements in HAM-D, HAM-A, BDI, and CGI-S scores. Cumulative response rates by HAM-D were 35.0 and 75.0 % at 4 and 8 weeks, respectively, corresponding cumulative remission rates by HAM-D were 15.0 and 55.0 %, respectively. No significant differences were found between pre- and post-treatment A score. Neurofeedback treatment could improve depressive symptoms significantly. In addition, anxiety symptoms and clinical illness severity decreased significantly after neurofeedback treatment. Despite its several limitations, such as, small sample size and lack of a control group, this study suggested neurofeedback has significant effects in patients with major depressive disorder. PMID:26392114

  2. 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.

  3. 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.

  4. A Randomized, Open-Label, Dose-Response Study of Losartan in Hypertensive Children

    Science.gov (United States)

    Wells, Thomas G.; Shahinfar, Shahnaz; Massaad, Rachid; Dankner, Wayne M.; Lam, Chun; Santoro, Emanuela Palumbo; McCrary Sisk, Christine; Blaustein, Robert O.

    2014-01-01

    Background and objectives Once-daily losartan reduces BP in a dose-dependent manner and is well tolerated in hypertensive children aged 6–16 years. This study assessed the dose-response relationship, safety, and tolerability of losartan in hypertensive children aged 6 months to 6 years. Design, setting, participants, & measurements This was a 12-week, randomized, open-label, dose-ranging study, with a 2-year extension. Patients were randomized to losartan at the following dosages: 0.1 mg/kg per day (low), 0.3 mg/kg per day (medium), or 0.7 mg/kg per day (high). Losartan was titrated to the next dose level (to a 1.4 mg/kg per day maximum dosage, not exceeding 100 mg/d, which was not one of the three original doses offered at randomization) at weeks 3, 6, and 9 for patients who did not attain their goal BP and were not taking the highest dose. Dose response was evaluated by analyzing the slope of change in sitting systolic BP (SBP; primary end point) and diastolic BP (DBP; secondary end point) after 3 weeks compared with baseline. Adverse events (AEs) were recorded throughout. Results Of the 101 patients randomized, 99 were included in the analysis (low dose, n=32; medium dose, n=34; and high dose, n=33). Mean sitting BP decreased from baseline in the low-, medium-, and high-dose groups by 7.3, 7.6, and 6.7 mmHg, respectively, for SBP and 8.2, 5.1, and 6.7 mmHg, respectively, for DBP after 3 weeks. No dose-response relationship was established by the slope analysis on SBP (P=0.75) or DBP (P=0.64). The BP-lowering effect was observed throughout the 2-year extension. The incidence of AEs was low and comparable between groups. Conclusions Hypertensive children aged 6 months to 6 years treated with losartan 0.1–0.7 mg/kg per day had clinically significant decreases from baseline in SBP and DBP, yet no dose-response relationship was evident. Losartan, at a dosage up to 1.4 mg/kg per day, was well tolerated. PMID:24875194

  5. An Open-Label Trial of Recombinant Human Insulin-Like Growth Factor-I/Recombinant Human Insulin-Like Growth Factor Binding Protein-3 (rhIGF-1/rhIGFBP-3) in Myotonic Dystrophy Type 1

    Science.gov (United States)

    Heatwole, Chad R.; Eichinger, Katy J.; Friedman, Deborah I.; Hilbert, James E.; Jackson, Carlayne E.; Logigian, Eric L.; Martens, William B.; McDermott, Michael P.; Pandya, Shree K.; Quinn, Christine; Smirnow, Alexis M.; Thornton, Charles A.; Moxley, Richard T.

    2012-01-01

    Objective To evaluate the safety and tolerability of recombinant human insulin-like growth factor-1 (rhIGF-1) complexed with IGF binding protein-3 (rhIGF-1/rhIGFBP-3) in patients with myotonic dystrophy type 1 (DM1). Design Open-label dose-escalation clinical trial. Setting University medical center. Participants Fifteen moderately affected ambulatory participants with genetically-proven DM1. Intervention Participants received escalating dosages of subcutaneous rhIGF-1/rhIGFBP-3 over 24 weeks followed by a 16 week washout period. Outcome Measures Serial assessments of safety, muscle mass, muscle function, and metabolic state were performed. The primary outcome variable was the ability of participants to complete 24 weeks on rhIGF-1/rhIGFBP-3 treatment. Results All participants tolerated rhIGF-1/rhIGFBP-3. There were no significant changes in muscle strength or functional outcomes measures. Lean body muscle mass measured by dual energy x-ray absorptiometry increased by 1.95 kg (p=0.0007) after treatment. Participants also experienced a mean reduction in triglyceride levels of 47 mg/dL (p=0.002), a mean increase in HDL levels of 5.0 mg/dL (p=0.03), a mean reduction in HbA1c of 0.15% (p=0.03), and a mean increase in testosterone level (in men) of 203 ng/dL (p=0.002) while on rhIGF-1/rhIGFBP-3. Mild reactions at the injection site occurred (n=9 participants), as did mild transient hypoglycemia (n=3), lightheadedness (n=2), and transient papilledema (n=1). Conclusions rhIGF-1/rhIGFBP-3 treatment was generally well tolerated in DM1. rhIGF-1/rhIGFBP-3 was associated with increased lean body mass and improvements in metabolism, but not with increased muscle strength or function. Larger randomized controlled trials would be needed to further evaluate the efficacy and safety of this medication in patients with neuromuscular disease. PMID:20837825

  6. Changes in serum lipids in patients with rheumatoid arthritis treated with a combination of tocilizumab and methotrexate compared with methotrexate alone for 24 weeks of observation

    Directory of Open Access Journals (Sweden)

    E. V. Udachkina

    2015-11-01

    Full Text Available Background. According to the some studies tocilizumab therapy (TCZ in patients with rheumatoid arthritis (RA is accompanied by deterioration of blood lipid profile. Aim. To study changes in serum lipid parameters in patients with RA treated with a combination of tocilizumab and methotrexate compared with methotrexate alone for 24 weeks of observation. Material and methods. Patients (n=72 with RA were included into the pilot non-randomized 24-week study and divided in two groups: 1 TCZ+MTX group (n=39; women 30; median age 51 [43-55] years; 6 i.v. infusions of TCZ 8 mg/kg + МТX 10-20 mg/week; 2 MTX group (n=33; women 23; mеdian age 56 [48-63] years; MTX 7.5-20 mg/week. Results. At the baseline, similar proatherogenic blood profile was observed in both groups. The patients of MTX group more frequently took statins (n=19; 57.6% compared with the group TCZ+MTX (n=7; 18%, (p<0.05. The lipid levels correlated positively with traditional risk factors (p<0.05. RA activity and duration correlated negatively with high density lipoprotein cholesterol (HDL-C, (p<0.05. Good/satisfactory anti-inflammatory effect was achieved in both groups after 24 weeks of treatment. Patients of TCZ+MTX group showed an increase in total cholesterol and HDL-C levels by 11% and 110%, respectively and decrease in plasma atherogenic index (PAI by 47%, (p<0.05. HDL-C level increased by 22% and PAI decreased by 16% in patients of MTX group (p<0.05. Among patients of MTX group without statin therapy HDL-C as well as non-HDL-C levels were increased by 24% and 27%, respectively (p<0.05; PAI did not change significantly in this subgroup. Among patients of MTX group treated with statins isolated increase in HDL-C level by 22% and decrease in PAI by 37.3% (p<0.05 were observed. A number of patients with achieved target levels of all studied lipid parameters did not change significantly in both groups. Conclusions. TCZ+MTX combined therapy as well as MTX monotherapy are associated

  7. 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...... and the occurrence of an infusion reaction. The few patients who did reach the primary endpoint showed improvement in all aspects studied. CONCLUSION: Infliximab combined with weekly methotrexate might be safe and well tolerated in a small subgroup of patients with drug-naive recent-onset myositis. At present, we do...

  8. Adherence and virologic suppression during the first 24 weeks on antiretroviral therapy among women in Johannesburg, South Africa - a prospective cohort study

    Directory of Open Access Journals (Sweden)

    Katzenstein David

    2011-02-01

    Full Text Available Abstract Background Adherence is a necessary part of successful antiretroviral treatment (ART. We assessed risk factors for incomplete adherence among a cohort of HIV-infected women initiating ART and examined associations between adherence and virologic response to ART. Methods A secondary data analysis was conducted on a cohort of 154 women initiating non-nucleoside reverse transcriptase inhibitor (NNRTI-based ART at a single site in Johannesburg, South Africa. Ninety women had been enrolled in a prevention of mother-to-child transmission (pMTCT program and were exposed to single-dose nevirapine (sdNVP >18 months earlier. Women were interviewed pre-treatment and clinical, virologic and adherence data were collected during follow-up to 24 weeks. Incomplete adherence to ART was defined as returning >5% of medications, estimated by pill counts at scheduled visits. Multivariable logistic regression analysis and unadjusted odds ratio (95%CI were performed, using STATA/SE (ver 10.1. Results About half of the women (53% were 400 copies/ml at 24 weeks and 37% had incomplete adherence at one or more visits. Incomplete adherence was associated with less education (p = 0.01 and lack of financial support from a partner (p = 0.02 after adjustment for confounders. Only when adherence levels dropped below 80% was there a significant association with viremia in the group overall (p = 0.02 although adherence Conclusion Virologic response to NNRTI-treatment in the cohort was excellent. However, women who received sdNVP were at greater risk of virologic failure when adherence was

  9. 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

  10. FG-3019 anti-connective tissue growth factor monoclonal antibody: results of an open-label clinical trial in idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Raghu, Ganesh; Scholand, Mary Beth; de Andrade, João; Lancaster, Lisa; Mageto, Yolanda; Goldin, Jonathan; Brown, Kevin K; Flaherty, Kevin R; Wencel, Mark; Wanger, Jack; Neff, Thomas; Valone, Frank; Stauffer, John; Porter, Seth

    2016-05-01

    FG-3019 is a fully human monoclonal antibody that interferes with the action of connective tissue growth factor, a central mediator in the pathogenesis of fibrosis.This open-label phase 2 trial evaluated the safety and efficacy of two doses of FG-3019 administered by intravenous infusion every 3 weeks for 45 weeks in patients with idiopathic pulmonary fibrosis (IPF). Subjects had a diagnosis of IPF within the prior 5 years defined by either usual interstitial pneumonia (UIP) pattern on a recent high-resolution computed tomography (HRCT) scan, or a possible UIP pattern on HRCT scan and a recent surgical lung biopsy showing UIP pattern. Pulmonary function tests were performed every 12 weeks, and changes in the extent of pulmonary fibrosis were measured by quantitative HRCT scans performed at baseline and every 24 weeks.FG-3019 was safe and well-tolerated in IPF patients participating in the study. Changes in fibrosis were correlated with changes in pulmonary function.Further investigation of FG-3019 in IPF with a placebo-controlled clinical trial is warranted and is underway. PMID:26965296

  11. Cinnarizine in migraine prophylaxis: efficacy, tolerability and predictive factors for therapeutic responsiveness. An open-label pilot trial.

    Science.gov (United States)

    Rossi, Paolo; Fiermonte, Giancarlo; Pierelli, Francesco

    2003-01-01

    The efficacy and tolerability of cinnarizine (75 mg, at bedtime) in migraine prophylaxis and the presence of possible predictive factors for therapeutic responsiveness were evaluated in an open-label pilot trial. Eighty consecutive outpatients suffering from migraine with or without aura participated in the study. After 12 weeks of therapy, 55 patients experienced a greater than 66% reduction in headache frequency and were considered responders. A significant reduction in the number of migraine days (mean reduction 58 +/- 8%) and in intake of medication to treat acute attacks (mean reduction 55 +/- 11%) was also observed. Cinnarizine was well tolerated, as documented by the low number of adverse effects. Failure to respond to previous prophylactic treatments was a negative predictive factor correlated with a poor prognosis. This study, even bearing in mind its limitations as an open-label trial, suggests that cinnarizine might be an effective prophylactic anti-migraine agent. The clinical characteristics of migraine patients do not help to predict response to treatment. PMID:14703897

  12. 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...

  13. 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.

  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. Treatment Compliance with Fixed-Dose Combination of Vildagliptin/Metformin in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Metformin Monotherapy: A 24-Week Observational Study

    Directory of Open Access Journals (Sweden)

    Grigorios Rombopoulos

    2015-01-01

    Full Text Available Objective. To evaluate the differences in treatment compliance with vildagliptin/metformin fixed-dose versus free-dose combination therapy in patients with type 2 diabetes mellitus (T2DM in Greece. Design. Adult patients with T2DM, inadequately controlled with metformin monotherapy, (850 mg bid, participated in this 24-week, multicenter, observational study. Patients were enrolled in two cohorts: vildagliptin/metformin fixed-dose combination (group A and vildagliptin metformin free-dose combination (group B. Results. 659 patients were enrolled, 360 were male, with mean BMI 30.1, mean T2DM duration 59.6 months, and mean HbA1c at baseline 8%; 366 patients were assigned to group A and 293 to group B; data for 3 patients was missing. In group A, 98.9% of patients were compliant with their treatment compared to 84.6% of group B. The odds ratio for compliance in group A versus B was (OR 18.9 (95% CI: 6.2, 57.7; P<0.001. In group A mean HbA1c decreased from 8.1% at baseline to 6.9% (P<0.001 at the study end and from 7.9% to 6.8% (P<0.001 in group B. Conclusions. Patients in group A were more compliant than patients in group B. These results are in accordance with international literature suggesting that fixed-dose combination therapies lead to increased compliance to treatment.

  16. The effect of mirtazapine in panic disorder : an open label pilot study with a single-blind placebo run-in period

    NARCIS (Netherlands)

    Boshuisen, ML; Slaap, BR; Vester-Blokland, ED; den Boer, JA

    2001-01-01

    In this open label pilot study, we studied the efficacy of mirtazapine (Remeron) in panic disorder. Twenty-eight patients with a DSM-IV diagnosis of panic disorder, with or without agoraphobia (10 males/18 females), were included and 19 patients completed the study. The 15-week trial started with a

  17. An Analysis of Patient Adherence to Treatment during a 1-Year, Open-Label Study of OROS[R] Methylphenidate in Children with ADHD

    Science.gov (United States)

    Faraone, Stephen V.; Biederman, Joseph; Zimmerman, Brenda

    2007-01-01

    Objective: Treatment adherence is an important aspect of ADHD symptom management, but there are many factors that may influence adherence. Method: This analysis assessed adherence to OROS methylphenidate during a 1-year, open-label study in children. Adherence was defined as the number of days medication was taken divided by the number of days in…

  18. 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…

  19. Neoadjuvant capecitabine, radiotherapy, and bevacizumab (CRAB in locally advanced rectal cancer: results of an open-label phase II study

    Directory of Open Access Journals (Sweden)

    Edhemovic Ibrahim

    2011-08-01

    Full Text Available Abstract Background Preoperative capecitabine-based chemoradiation is a standard treatment for locally advanced rectal cancer (LARC. Here, we explored the safety and efficacy of the addition of bevacizumab to capecitabine and concurrent radiotherapy for LARC. Methods Patients with MRI-confirmed stage II/III rectal cancer received bevacizumab 5 mg/kg i.v. 2 weeks prior to neoadjuvant chemoradiotherapy followed by bevacizumab 5 mg/kg on Days 1, 15 and 29, capecitabine 825 mg/m2 twice daily on Days 1-38, and concurrent radiotherapy 50.4 Gy (1.8 Gy/day, 5 days/week for 5 weeks + three 1.8 Gy/day, starting on Day 1. Total mesorectal excision was scheduled 6-8 weeks after completion of chemoradiotherapy. Tumour regression grades (TRG were evaluated on surgical specimens according to Dworak. The primary endpoint was pathological complete response (pCR. Results 61 patients were enrolled (median age 60 years [range 31-80], 64% male. Twelve patients (19.7% had T3N0 tumours, 1 patient T2N1, 19 patients (31.1% T3N1, 2 patients (3.3% T2N2, 22 patients (36.1% T3N2 and 5 patients (8.2% T4N2. Median tumour distance from the anal verge was 6 cm (range 0-11. Grade 3 adverse events included dermatitis (n = 6, 9.8%, proteinuria (n = 4, 6.5% and leucocytopenia (n = 3, 4.9%. Radical resection was achieved in 57 patients (95%, and 42 patients (70% underwent sphincter-preserving surgery. TRG 4 (pCR was recorded in 8 patients (13.3% and TRG 3 in 9 patients (15.0%. T-, N- and overall downstaging rates were 45.2%, 73.8%, and 73.8%, respectively. Conclusions This study demonstrates the feasibility of preoperative chemoradiotherapy with bevacizumab and capecitabine. The observed adverse events of neoadjuvant treatment are comparable with those previously reported, but the pCR rate was lower.

  20. Neoadjuvant capecitabine, radiotherapy, and bevacizumab (CRAB) in locally advanced rectal cancer: results of an open-label phase II study

    OpenAIRE

    Edhemovic Ibrahim; Oblak Irena; Anderluh Franc; Bracko Matej; Music Maja; Ocvirk Janja; Velenik Vaneja; Brecelj Erik; Kropivnik Mateja; Omejc Mirko

    2011-01-01

    Abstract Background Preoperative capecitabine-based chemoradiation is a standard treatment for locally advanced rectal cancer (LARC). Here, we explored the safety and efficacy of the addition of bevacizumab to capecitabine and concurrent radiotherapy for LARC. Methods Patients with MRI-confirmed stage II/III rectal cancer received bevacizumab 5 mg/kg i.v. 2 weeks prior to neoadjuvant chemoradiotherapy followed by bevacizumab 5 mg/kg on Days 1, 15 and 29, capecitabine 825 mg/m2 twice daily on ...

  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. Neoadjuvant capecitabine, radiotherapy, and bevacizumab (CRAB) in locally advanced rectal cancer: results of an open-label phase II study

    International Nuclear Information System (INIS)

    Preoperative capecitabine-based chemoradiation is a standard treatment for locally advanced rectal cancer (LARC). Here, we explored the safety and efficacy of the addition of bevacizumab to capecitabine and concurrent radiotherapy for LARC. Patients with MRI-confirmed stage II/III rectal cancer received bevacizumab 5 mg/kg i.v. 2 weeks prior to neoadjuvant chemoradiotherapy followed by bevacizumab 5 mg/kg on Days 1, 15 and 29, capecitabine 825 mg/m2 twice daily on Days 1-38, and concurrent radiotherapy 50.4 Gy (1.8 Gy/day, 5 days/week for 5 weeks + three 1.8 Gy/day), starting on Day 1. Total mesorectal excision was scheduled 6-8 weeks after completion of chemoradiotherapy. Tumour regression grades (TRG) were evaluated on surgical specimens according to Dworak. The primary endpoint was pathological complete response (pCR). 61 patients were enrolled (median age 60 years [range 31-80], 64% male). Twelve patients (19.7%) had T3N0 tumours, 1 patient T2N1, 19 patients (31.1%) T3N1, 2 patients (3.3%) T2N2, 22 patients (36.1%) T3N2 and 5 patients (8.2%) T4N2. Median tumour distance from the anal verge was 6 cm (range 0-11). Grade 3 adverse events included dermatitis (n = 6, 9.8%), proteinuria (n = 4, 6.5%) and leucocytopenia (n = 3, 4.9%). Radical resection was achieved in 57 patients (95%), and 42 patients (70%) underwent sphincter-preserving surgery. TRG 4 (pCR) was recorded in 8 patients (13.3%) and TRG 3 in 9 patients (15.0%). T-, N- and overall downstaging rates were 45.2%, 73.8%, and 73.8%, respectively. This study demonstrates the feasibility of preoperative chemoradiotherapy with bevacizumab and capecitabine. The observed adverse events of neoadjuvant treatment are comparable with those previously reported, but the pCR rate was lower

  3. Safety, tolerability and clinical pharmacology of dabigatran etexilate in adolescents. An open-label phase IIa study.

    Science.gov (United States)

    Halton, Jacqueline M L; Lehr, Thorsten; Cronin, Lisa; Lobmeyer, Maximilian T; Haertter, Sebastian; Belletrutti, Mark; Mitchell, Lesley G

    2016-08-30

    Venous thromboembolism (VTE) incidence is increasing among children owing to many factors, including improved diagnosis of VTE. There is a need for alternative treatment options. Our objective was to investigate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of dabigatran etexilate in adolescents with VTE. Adolescents aged 12 to ECT) was linear; the relationship with activated partial thromboplastin time (aPTT) was non-linear. Adult population PK/PD models predicted the adolescent concentration-ECT and -aPTT relationships well. In conclusion, dabigatran etexilate was generally well tolerated, except for occurrence of dyspepsia in two patients, over the three-day treatment period. The dabigatran PK/PD relationship observed in adolescent patients was similar to that in adult patients. PMID:27357738

  4. 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. PMID:25231176

  5. Open-label study of the short-term effects of memantine on FDG-PET in frontotemporal dementia

    Directory of Open Access Journals (Sweden)

    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

  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. 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.

  8. COMPARISON OF THE INFLUENCE OF LONG-TERM TREATMENT BASED ON CARVEDILOL OR BISOPROLOL ON METABOLIC PARAMETERS IN HYPERTENSIVE PATIENTS WITH OVERWEIGHT OR OBESITY RESULTS OF THE RANDOMIZED OPEN-LABEL PARALLEL-GROUPS STEPPED TRIAL CABRIOLET (PART I

    Directory of Open Access Journals (Sweden)

    S. Y. Martsevich

    2015-12-01

    Full Text Available Aim. To compare antihypertensive and metabolic effects of long-term treatment with carvedilol or bisoprolol in patients with arterial hypertension (HT of 1-2 degree and overweight/obesity. Material and methods. A total of 105 patients were enrolled into open-label comparative stepped trial in two parallel groups. The patients were randomized into two groups: the group 1 (n=53 started treatment with carvedilol 25 mg daily and the group 2 (n=52 – with bisoprolol 5 mg daily. If the effect was insufficient a dose of a beta-blocker was doubled, then amlodipine was added in the dose of 5 mg daily with its further increase if necessary or indapamide in dose 1.5 mg daily. The follow-up for each patient was 24 weeks. At the start and then 12 and 24 weeks later the frequency of target blood pressure (BP achievement, body mass index, biochemical indices, ECG and treatment safety were evaluated. Results. Significant distinctions in antihypertensive therapy effect between the groups were absent (ΔBP=-29.5±11.3/17.8±8.4 and -30.4±12.8/18.7±8 mm Hg for groups 1 and 2, respectively , p<0.001 for the both groups as well as the necessity for additional therapy. All the patients completed the study had achieved target BP level. The patients of the both groups decreased body mass index after 6-month treatment (-0.57±1.1, p=0.001 and -0.53±0.8 kg/m2, p<0.001 for groups 1 and 2, respectively. Patients of the group 1 demonstrated significant reduction in fasting plasma glucose level (-0.45±1.2 mM/l, p=0.01, uric acid (-0.05±0.01 mM/l, p<0.001 and low-density lipoprotein cholesterol level (-0.28±0.9 mM/l, p<0.05 as well as a trend for HOMA index decrease. Serum creatinine level increased in patients of the group 2 (6.35±22.4 mcM/l, p=0.05 with no significant dynamics in metabolic indices. Glomerular filtration rate did not change significantly in the group 1, while there was significant decrease in the group 2 (Δ-3.8±15.2 ml/min/1,73m2, р=0.01. The

  9. COMPARISON OF THE INFLUENCE OF LONG-TERM TREATMENT BASED ON CARVEDILOL OR BISOPROLOL ON METABOLIC PARAMETERS IN HYPERTENSIVE PATIENTS WITH OVERWEIGHT OR OBESITY RESULTS OF THE RANDOMIZED OPEN-LABEL PARALLEL-GROUPS STEPPED TRIAL CABRIOLET (PART I

    Directory of Open Access Journals (Sweden)

    S. Y. Martsevich

    2012-01-01

    Full Text Available Aim. To compare antihypertensive and metabolic effects of long-term treatment with carvedilol or bisoprolol in patients with arterial hypertension (HT of 1-2 degree and overweight/obesity. Material and methods. A total of 105 patients were enrolled into open-label comparative stepped trial in two parallel groups. The patients were randomized into two groups: the group 1 (n=53 started treatment with carvedilol 25 mg daily and the group 2 (n=52 – with bisoprolol 5 mg daily. If the effect was insufficient a dose of a beta-blocker was doubled, then amlodipine was added in the dose of 5 mg daily with its further increase if necessary or indapamide in dose 1.5 mg daily. The follow-up for each patient was 24 weeks. At the start and then 12 and 24 weeks later the frequency of target blood pressure (BP achievement, body mass index, biochemical indices, ECG and treatment safety were evaluated. Results. Significant distinctions in antihypertensive therapy effect between the groups were absent (ΔBP=-29.5±11.3/17.8±8.4 and -30.4±12.8/18.7±8 mm Hg for groups 1 and 2, respectively , p<0.001 for the both groups as well as the necessity for additional therapy. All the patients completed the study had achieved target BP level. The patients of the both groups decreased body mass index after 6-month treatment (-0.57±1.1, p=0.001 and -0.53±0.8 kg/m2, p<0.001 for groups 1 and 2, respectively. Patients of the group 1 demonstrated significant reduction in fasting plasma glucose level (-0.45±1.2 mM/l, p=0.01, uric acid (-0.05±0.01 mM/l, p<0.001 and low-density lipoprotein cholesterol level (-0.28±0.9 mM/l, p<0.05 as well as a trend for HOMA index decrease. Serum creatinine level increased in patients of the group 2 (6.35±22.4 mcM/l, p=0.05 with no significant dynamics in metabolic indices. Glomerular filtration rate did not change significantly in the group 1, while there was significant decrease in the group 2 (Δ-3.8±15.2 ml/min/1,73m2, р=0.01. The

  10. 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.

  11. A Prospective, Open-Label Study of Low-Dose Total Skin Electron Beam Therapy in Mycosis Fungoides

    International Nuclear Information System (INIS)

    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 fractions over 4 successive days. Results: Two patients had a complete clinical response but relapsed after 3.5 months. Six patients had partial clinical responses, with a mean duration of 2.0 months. One patient had no clinical response. Median time to relapse was 2.7 months. One patient died of unrelated 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 of remission is short. Low-dose total skin electron beam therapy may find application in palliative treatment of mycosis fungoides because of limited toxicity and the possibility of repeating treatments for long-term disease control

  12. 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.

  13. 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.

  14. 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

  15. 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...

  16. An Open-Label Investigation of the Pharmacokinetic Profiles of Lisdexamfetamine Dimesylate and Venlafaxine Extended-Release, Administered Alone and in Combination, in Healthy Adults

    OpenAIRE

    Ermer, James; Haffey, Mary B; Richards, Cynthia; Lasseter, Kenneth; Roesch, Benno; Purkayastha, Jaideep; Corcoran, Mary; Harlin, Bree; Martin, Patrick

    2013-01-01

    Background Lisdexamfetamine dimesylate (LDX), a prodrug consisting of d-amphetamine and l-lysine, is being studied in clinical trials of major depressive disorder. Additional drug-drug interaction studies were warranted. Objective This study aimed to describe the pharmacokinetics and safety of LDX and venlafaxine extended-release (VXR), alone or combined. Study Design The study was an open-label, two-arm, single-sequence crossover investigation with randomization to treatment sequence. Settin...

  17. Abacavir, zidovudine, or stavudine as paediatric tablets for African HIV-infected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial

    OpenAIRE

    V Mulenga; Musiime, V.; Kekitiinwa, A.; Cook, AD; G Abongomera; Kenny, J.; Chabala, C; Mirembe, G.; Asiimwe, A; Owen-Powell, E.; Burger, D.; McIlleron, H.; N. Klein; Chintu, C; Thomason, MJ

    2015-01-01

    Summary Background WHO 2013 guidelines recommend universal treatment for HIV-infected children younger than 5 years. No paediatric trials have compared nucleoside reverse-transcriptase inhibitors (NRTIs) in first-line antiretroviral therapy (ART) in Africa, where most HIV-infected children live. We aimed to compare stavudine, zidovudine, or abacavir as dual or triple fixed-dose-combination paediatric tablets with lamivudine and nevirapine or efavirenz. Methods In this open-label, parallel-gro...

  18. Safety and Efficacy of Tetrabenazine and Use of Concomitant Medications During Long-Term, Open-Label Treatment of Chorea Associated with Huntington’s and Other Diseases

    OpenAIRE

    Shen, Vivienne; Clarence-Smith, Kathleen; Hunter, Christine; Jankovic, Joseph

    2013-01-01

    Background Although tetrabenazine, a drug that depletes presynaptic dopamine by inhibiting vesicular monoamine transporter 2 (VMAT2), was approved by the U.S. Food and Drug Administration in 2008 for the treatment of chorea associated with Huntington’s disease (HD), there is a paucity of data on its long-term efficacy and safety. Methods Approximately 2,000 patients with a variety of hyperkinetic movement disorders had been treated with open-label tetrabenazine at the Movement Disorders Clini...

  19. Effect of Vitamin D supplementation on glycemic parameters and progression of prediabetes to diabetes: A 1-year, open-label randomized study

    OpenAIRE

    Mohammad Shafi Kuchay; Bashir Ahmad Laway; Mir Iftikhar Bashir; Arshad Iqbal Wani; Raiz Ahmad Misgar; Zaffar Amin Shah

    2015-01-01

    Background: Whether Vitamin D supplementation in prediabetes subjects prevents the development of diabetes is a matter of debate, and the results are inconsistent. This open-label, randomized study in subjects with prediabetes evaluated the effect of 12 months of Vitamin D supplementation on glycemic parameters and progression of prediabetes to diabetes in an ethnically homogeneous Kashmiri population. Materials and Methods: A total of 147 subjects were diagnosed as prediabetes out of which 1...

  20. 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

  1. Preliminary open-label clinical evaluation of the soothing and reepithelialization properties of a novel topical formulation for rosacea

    Directory of Open Access Journals (Sweden)

    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

  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. An open label follow-up study on amisulpride in the add-on treatment of bipolar I patients

    Directory of Open Access Journals (Sweden)

    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.

  4. 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

  5. Geographical variation in the response of visceral leishmaniasis to paromomycin in East Africa: a multicentre, open-label, randomized trial.

    Directory of Open Access Journals (Sweden)

    Asrat Hailu

    Full Text Available BACKGROUND: Visceral leishmaniasis (VL is a major health problem in developing countries. The untreated disease is fatal, available treatment is expensive and often toxic, and drug resistance is increasing. Improved treatment options are needed. Paromomycin was shown to be an efficacious first-line treatment with low toxicity in India. METHODS: This was a 3-arm multicentre, open-label, randomized, controlled clinical trial to compare three treatment regimens for VL in East Africa: paromomycin sulphate (PM at 15 mg/kg/day for 21 days versus sodium stibogluconate (SSG at 20 mg/kg/day for 30 days; and the combination of both dose regimens for 17 days. The primary efficacy endpoint was cure based on parasite-free tissue aspirates taken 6 months after treatment. FINDINGS: Overall, 135 patients per arm were enrolled at five centres in Sudan (2 sites, Kenya (1 and Ethiopia (2, when the PM arm had to be discontinued due to poor efficacy. The trial has continued with the higher dose of PM as well as the combination of PM and SSG arms. These results will be reported later. Baseline patient characteristics were similar among treatment arms. The overall cure with PM was significantly inferior to that with SSG (63.8% versus 92.2%; difference 28.5%, 95%CI 18.8% to 38.8%, p<0.001. The efficacy of PM varied among centres and was significantly lower in Sudan (14.3% and 46.7% than in Kenya (80.0% and Ethiopia (75.0% and 96.6%. No major safety issues with PM were identified. CONCLUSION: The efficacy of PM at 15 mg/kg/day for 21 days was inadequate, particularly in Sudan. The efficacy of higher doses and the combination treatment warrant further studies.

  6. Urate Lowering Therapy with Febuxostat in Daily Practice—A Multicentre, Open-Label, Prospective Observational Study

    Directory of Open Access Journals (Sweden)

    Anne-Kathrin Tausche

    2014-01-01

    Full Text Available Introduction. Febuxostat, a novel xanthine oxidase inhibitor for the treatment of symptomatic hyperuricemia, showed superiority over allopurinol in the reduction of serum uric acid levels in pivotal studies. Whether this holds true the FORTE (febuxostat in the oral urate lowering treatment: effectiveness and safety study was conducted to evaluate treatment with febuxostat under daily practice conditions. Materials/Methods. The multicentre, open-label, and prospective observational study was conducted in 1,690 German medical practices from 9/2010 to 5/2011. Safety and efficacy data were assessed at baseline and week 4. Results. Data from 5,592 gout patients (72.6% male, mean age 63.7 years were collected. Under urate lowering treatment with febuxostat mean serum uric acid levels decreased significantly from 8.9±1.9 mg/dL (534.0±114.6 μmol/L at baseline to 6.2±2.5 mg/dL (372.0±150.0 μmol/L at week 4. 67% which reached the mean uric acid target (6.1±1.0 mg/dL [366.0±59.4 μmol/L]. Only 43.1% of patients received concomitant flare prophylaxis. A total of 178 adverse events (mostly gout flares were reported in 152 patients (2.6%. Conclusion. Febuxostat lowers serum uric acid levels effectively in routine clinical practice. Overall, treatment with febuxostat in both available dosages (80 mg/120 mg was safe and well tolerated.

  7. Effects of quetiapine and olanzapine in patients with psychosis and violent behavior: a pilot randomized, open-label, comparative study

    Directory of Open Access Journals (Sweden)

    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

  8. 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.

  9. Transdermal fentanyl improves pain control and functionality in patients with osteoarthritis: an open-label Canadian trial.

    Science.gov (United States)

    Choquette, Denis; McCarthy, Timothy G; Rodrigues, Jude F N; Kelly, Allan J; Camacho, Fernando; Horbay, G L A; Husein-Bhabha, Farah A

    2008-05-01

    Current treatment guidelines advocate opioids for arthritis when standard analgesics produce inadequate relief. Efficacy, adverse effects (AEs), dosing regimens, physician expertise and patient preference influence treatment selection. This study assessed transdermal fentanyl (TDF) as a treatment option for osteoarthritis (OA) patients. This prospective, Canadian open-label, 8-week trial assessed the efficacy and safety of TDF in patients with OA of hip or knee with moderate-to-severe target joint pain inadequately controlled using weak opioids. TDF was initiated at 25 mcg/h and titrated to optimal pain control. Rescue acetaminophen 500 mg was allowed (maximum 4 g/day). The main endpoint was improvement in pain control assessment rating (five rating categories); pain intensity (0-10 numerical scale), functionality (WOMAC-OA Index), health-related quality of life (SF-36 Health Survey) and global impression were also evaluated. Eighty-one patients (61% female, mean age 60 years) were enrolled; 62 were evaluable. All had failed on previous weak opioid therapy, primarily codeine or codeine combinations. At treatment end, 65% rated pain control as improved (Pain Control Assessment rating change >or=1 category; pacetaminophen. At 1 month and end of treatment, changes in the SF-36 physical global scale and individual sub-scores for the pain index and role-physical scales were highly significant (pdizziness and vomiting. Most treatment-related AEs were mild to moderate in intensity. TDF improved pain control, functionality and health-related quality of life in these patients. The findings support current recommendations for use of opioids such as TDF as a treatment option for a sub-population of patients with OA pain. PMID:18038178

  10. Single-center open-label randomized study of anemia management improvement in ESRD patients with secondary hyperparathyroidism

    Directory of Open Access Journals (Sweden)

    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.

  11. Sativex long-term use: an open-label trial in patients with spasticity due to multiple sclerosis.

    Science.gov (United States)

    Serpell, Michael G; Notcutt, William; Collin, Christine

    2013-01-01

    Sativex is an endocannabinoid system modulator principally containing Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD). During a 6-week randomised controlled trial, Sativex had a clinically relevant effect on spasticity associated with multiple sclerosis (MS). Patients self-titrated oromucosal Sativex to symptom relief or maximum tolerated dose (maximum of 130 mg THC and 120 mg CBD daily). The primary objective was to evaluate the safety and tolerability of long-term treatment by recording the incidence and severity of adverse events (AEs). Secondary outcomes were to determine evidence of developing tolerance and to assess the long-term dosing profile of Sativex. A validated 11-point Numerical Rating Scale of spasticity severity was used to assess efficacy. A total of 146 patients elected to enter this open-label follow-up safety trial. Mean treatment exposure was 334 days (standard deviation, SD = 209 days), and patients administered on average 7.3 (SD = 4.42) actuations per day. Fifty-two (36 %) patients withdrew from the study in the first year, 14 % due to AEs and 9 % due to lack of efficacy. Most AEs were mild/moderate in severity. Common (>10 %) treatment-related AEs were dizziness (24.7 %) and fatigue (12.3 %). Serious AEs occurred in five patients (3.4 %), with two psychiatric events reported by one patient. No psychoses, psychiatric AE trends, or withdrawal symptoms occurred following abrupt cessation of treatment. Baseline symptoms including spasticity did not deteriorate but were maintained to study completion in those patients who did not withdraw. No new safety concerns were identified with chronic Sativex treatment, and serious AEs were uncommon. There was no evidence of tolerance developing, and patients who remained in the study reported continued benefit. PMID:22878432

  12. 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

    2016-05-01

    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).

  13. 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

  14. 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

  15. 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

  16. 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

  17. Cohort Analysis of a 24-Week Randomized Controlled Trial to Assess the Efficacy of a Novel, Partial Meal Replacement Program Targeting Weight Loss and Risk Factor Reduction in Overweight/Obese Adults.

    Science.gov (United States)

    Brindal, Emily; Hendrie, Gilly A; Taylor, Pennie; Freyne, Jill; Noakes, Manny

    2016-01-01

    Our aim was to design and evaluate a weight-loss program, including a partial meal replacement program, point-of-care testing and face-to-face and smartphone app support, appropriate for delivery in a community pharmacy setting. Overweight or obese adults (n = 146, 71.2% female, 48.18 ± 11.75 years old) were recruited to participate in a 24-week weight loss study and randomised to two app conditions. The dietary intervention was consistent regardless of app. Twelve weeks of clinic appointments with a trained consultant were followed by only app support for an additional 12 weeks. By week 24, retention was 57.5%. There were no differences between app conditions. Based on a cohort analysis of the trial, the mean decrease in weight from baseline to week 24 was 6.43 ± 1.06 kg for males (p health outcomes over 24 weeks. PMID:27153085

  18. Modifications in Lipid Levels Are Independent of Serum TNF-α in Rheumatoid Arthritis: Results of an Observational 24-Week Cohort Study Comparing Patients Receiving Etanercept Plus Methotrexate or Methotrexate as Monotherapy

    Directory of Open Access Journals (Sweden)

    Norma Alejandra Rodriguez-Jimenez

    2014-01-01

    Full Text Available Objective. To compare the modifications in lipids between patients with rheumatoid arthritis (RA receiving etanercept plus methotrexate (ETA + MTX versus methotrexate (MTX and their relationship with serum levels of tumor necrosis factor-alpha (TNF-α. Methods. In an observational cohort study, we compared changes in lipid levels in patients receiving ETA + MTX versus MTX in RA. These groups were assessed at baseline and at 4 and 24 weeks, measuring clinical outcomes, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C, low-density lipoprotein cholesterol, and TNF-α. Results. Baseline values for lipid levels were similar in both groups. HDL-C levels increased significantly only in the ETA + MTX group (from 45.5 to 50.0 mg/dL at 4 weeks, a 10.2% increase, P<0.001, and to 56.0 mg/dL at 24 weeks, a 25.1% increase, P<0.001, while other lipids underwent no significant changes. ETA + MTX also exhibited a significant increase in TNF-α (44.8 pg/mL at baseline versus 281.4 pg/mL at 24 weeks, P<0.001. The MTX group had no significant changes in lipids or TNF-α. Significant differences in HDL-C between groups were observed at 24 weeks (P=0.04 and also in TNF-α  (P=0.01. Conclusion. HDL-C levels increased significantly following treatment with ETA + MTX, without a relationship with decrease of TNF-α.

  19. "Antifibrotic effect after low-dose imatinib mesylate treatment in patients with nephrogenic systemic fibrosis: An open-label non-randomized, uncontrolled clinical trial"

    DEFF Research Database (Denmark)

    Elmholdt, Tina Rask; Olesen, Anne Braae

    2011-01-01

    of skin fibrosis and increase in joint mobility evaluated by the modified Rodnan skin score and a goniometer. Results In two patients, the imatinib mesylate dose was reduced to 200 mg⁄ day and in one patient to 100 mg⁄ day. Two patients were treated for 24 weeks, one patient for 16 weeks and one patient...

  20. 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

  1. Transarterial Chemoembolization of Unresectable Hepatocellular Carcinoma with Drug Eluting Beads: Results of an Open-Label Study of 62 Patients

    International Nuclear Information System (INIS)

    The purpose of this study was to assess the safety and efficacy of doxorubicin-loaded beads (DC Beads) delivered by transarterial embolization for the treatment of unresectable hepatocellular carcinoma (HCC). This open-label, single-center, single-arm study included 62 cirrhotic patients with documented single unresectable HCC. Mean tumor diameter was 5.6 cm (range, 3-9 cm) classified as Okuda stages 1 (n = 53) and 2 (n = 9). Patients received repeat embolizations with doxorubicin-loaded beads every 3 months (maximum of three). The maximum doxorubicin dose was 150 mg per embolization, loaded in DC Beads of 100-300 or 300-500 μm. Regarding efficacy, overall, an objective response according to the European Association for the Study of the Liver criteria was observed in 59.6%, 81.8%, and 70.8% across three treatments. A complete response was observed in 4.8% after the first procedure and 3.6% and 8.3% after the second and third procedures, respectively. At 9 months a complete response was seen in 12.2%, an objective response in 80.7%, progressive disease in 6.8%, and 12.2% showed stable disease. Mean tumor necrosis ranged from 77.4% to 83.9% (range, 28.6%-100%) across three treatments. α-Fetoprotein levels showed a mean decrease of 1123 ng/ml (95% CI = 846-1399; p = 3 x 10-11) after the first session and remained stable after the second and third embolizations (42 and 70 ng/ml decrease, respectively). Regarding safety, bilirubin, γ-glutamyl transferase, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase showed only transient increases during the study period. Severe procedure-related complications were seen in 3.2% (cholecystitis, n 1; liver abscess, n = 1). Postembolization syndrome was observed in all patients. We conclude that hemoembolization using doxorubicin-loaded DC Beads is a safe and effective treatment of HCC as demonstrated by the low complication rate, increased tumor response, and sustained reduction of

  2. 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

  3. Palonosetron versus ondansetron as rescue medication for postoperative nausea and vomiting: a randomized, multicenter, open-label study

    Science.gov (United States)

    2014-01-01

    Background This study compared palonosetron and ondansetron as rescue medications for postoperative nausea and vomiting (PONV) in patients who received prophylactic ondansetron. Although guidelines recommend use of an agent from a different class when prophylaxis has failed, palonosetron has unique properties relative to other serotonin 5-HT3 receptor antagonists. Prior trials assessing its use for rescue have had conflicting results. Although palonosetron has compared favorably with ondansetron for PONV prevention, the drugs have not been compared in the rescue setting of failure of 5-HT3 receptor antagonist prophylaxis. Methods This was a randomized, open-label, multicenter trial comparing the efficacy and safety of intravenous palonosetron 0.075 mg and intravenous ondansetron 4 mg in patients experiencing PONV following laparoscopic abdominal or gynecological surgery despite prophylactic ondansetron. Results Of 239 patients screened, 220 were enrolled and 98 were treated for PONV: 48 and 50 in the palonosetron and ondansetron arms, respectively. Complete control during 72 hours after study drug administration was achieved in 25.0% of palonosetron recipients and 18.0% of ondansetron recipients (95% confidence interval [CI], -9.2, 23.3; p = 0.40). Corresponding incidences of vomiting were 29.2% for palonosetron and 48.0% for ondansetron (95% CI, -0.06, 37.7; p = 0.057), and 62.5% and 56.0% required additional rescue treatment, respectively (95% CI, -25.9, 12.9; p = 0.52). Other than a similar incidence of procedural pain in the 2 groups, the most common treatment-emergent adverse events, which were generally mild, were headache (14.6% vs 12.0%), constipation (8.3% vs 10.0%), and dizziness (6.3% vs 8.0%), for the palonosetron and ondansetron groups, respectively. Conclusions Palonosetron and ondansetron did not show differences in the primary efficacy endpoint of CC during the 72 hours after study drug administration. There was a trend toward less

  4. Tribendimidine and albendazole for treating soil-transmitted helminths, Strongyloides stercoralis and Taenia spp.: open-label randomized trial.

    Directory of Open Access Journals (Sweden)

    Peter Steinmann

    Full Text Available BACKGROUND: Tribendimidine is an anthelminthic drug with a broad spectrum of activity. In 2004 the drug was approved by Chinese authorities for human use. The efficacy of tribendimidine against soil-transmitted helminths (Ascaris lumbricoides, hookworm, and Trichuris trichiura has been established, and new laboratory investigations point to activity against cestodes and Strongyloides ratti. METHODOLOGY/PRINCIPAL FINDINGS: In an open-label randomized trial, the safety and efficacy of a single oral dose of albendazole or tribendimidine (both drugs administered at 200 mg for 5- to 14-year-old children, and 400 mg for individuals > or = 15 years against soil-transmitted helminths, Strongyloides stercoralis, and Taenia spp. were assessed in a village in Yunnan province, People's Republic of China. The analysis was on a per-protocol basis and the trial is registered with controlled-trials.com (number ISRCTN01779485. Both albendazole and tribendimidine were highly efficacious against A. lumbricoides and, moderately, against hookworm. The efficacy against T. trichiura was low. Among 57 individuals who received tribendimidine, the prevalence of S. stercoralis was reduced from 19.3% to 8.8% (observed cure rate 54.5%, p = 0.107, and that of Taenia spp. from 26.3% to 8.8% (observed cure rate 66.7%, p = 0.014. Similar prevalence reductions were noted among the 66 albendazole recipients. Taking into account "new" infections discovered at treatment evaluation, which were most likely missed pre-treatment due to the lack of sensitivity of available diagnostic approaches, the difference between the drug-specific net Taenia spp. cure rates was highly significant in favor of tribendimidine (p = 0.001. No significant adverse events of either drug were observed. CONCLUSIONS/SIGNIFICANCE: Our results suggest that single-dose oral tribendimidine can be employed in settings with extensive intestinal polyparasitism, and its efficacy against A. lumbricoides and hookworm

  5. 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

  6. An Open-label, Randomized Comparison of Levofloxacin and Amoxicillin/ Clavulanate plus Clarithromycin for the Treatment of Hospitalized Patients with Community-acquired Pneumonia

    OpenAIRE

    Han-Pin Kuo; Ling-Ling Hsieh; Chih-Ten Yu; Horng-Chyuan Lin; Chien-Ying Liu; Min-Li Chang; Chun-Hua Wang; Yu-Min Wang; Chih-Jan Wang; Hao-Cheng Chen; Shu-Min Lin; Ting-Yu Lin; Chien-Da Huang

    2007-01-01

    Background: Anti-pneumococcal fluoroquinolone has been used to treat communityacquiredpneumonia (CAP) frequently because of its broad antimicrobialspectrum.Methods: This randomized, open-label study was conducted in a tertiary teaching hospital.Eligible patients were randomized to levofloxacin 500 mg IV q24h followedby 500 mg orally q24h or a combination of amoxicillin/clavulanate500 mg/100 mg IV q8h with oral clarithromycin 500 mg q12h and then oralamoxicillin/clavulanate 250 mg/125 mg q8h w...

  7. Retraction statement: Manuka honey vs. hydrogel - a prospective, open label, multicentre, randomised controlled trial to compare desloughing efficacy and healing outcomes in venous ulcers.

    Science.gov (United States)

    2015-09-01

    The following article from Journal of Clinical Nursing, 'Manuka honey vs. hydrogel - a prospective, open label, multicentre, randomised controlled trial to compare desloughing efficacy and healing outcomes in venous ulcers' by Georgina Gethin and Seamus Cowman published online on 25 August 2008 in Wiley Online Library (wileyonlinelibrary.com) and in Volume 18, pp. 466-474, has been retracted by agreement between the journal Editor-in-Chief, the authors and John Wiley & Sons, Ltd. The retraction has been agreed due to errors in the data analysis which affect the article's findings.

  8. Gatifloxacin versus ceftriaxone for uncomplicated enteric fever in Nepal: an open-label, two-centre, randomised controlled trial

    Science.gov (United States)

    Arjyal, Amit; Basnyat, Buddha; Nhan, Ho Thi; Koirala, Samir; Giri, Abhishek; Joshi, Niva; Shakya, Mila; Pathak, Kamal Raj; Mahat, Saruna Pathak; Prajapati, Shanti Pradhan; Adhikari, Nabin; Thapa, Rajkumar; Merson, Laura; Gajurel, Damodar; Lamsal, Kamal; Lamsal, Dinesh; Yadav, Bharat Kumar; Shah, Ganesh; Shrestha, Poojan; Dongol, Sabina; Karkey, Abhilasha; Thompson, Corinne N; Thieu, Nga Tran Vu; Thanh, Duy Pham; Baker, Stephen; Thwaites, Guy E; Wolbers, Marcel; Dolecek, Christiane

    2016-01-01

    Summary Background Because treatment with third-generation cephalosporins is associated with slow clinical improvement and high relapse burden for enteric fever, whereas the fluoroquinolone gatifloxacin is associated with rapid fever clearance and low relapse burden, we postulated that gatifloxacin would be superior to the cephalosporin ceftriaxone in treating enteric fever. Methods We did an open-label, randomised, controlled, superiority trial at two hospitals in the Kathmandu valley, Nepal. Eligible participants were children (aged 2–13 years) and adult (aged 14–45 years) with criteria for suspected enteric fever (body temperature ≥38·0°C for ≥4 days without a focus of infection). We randomly assigned eligible patients (1:1) without stratification to 7 days of either oral gatifloxacin (10 mg/kg per day) or intravenous ceftriaxone (60 mg/kg up to 2 g per day for patients aged 2–13 years, or 2 g per day for patients aged ≥14 years). The randomisation list was computer-generated using blocks of four and six. The primary outcome was a composite of treatment failure, defined as the occurrence of at least one of the following: fever clearance time of more than 7 days after treatment initiation; the need for rescue treatment on day 8; microbiological failure (ie, blood cultures positive for Salmonella enterica serotype Typhi, or Paratyphi A, B, or C) on day 8; or relapse or disease-related complications within 28 days of treatment initiation. We did the analyses in the modified intention-to-treat population, and subpopulations with either confirmed blood-culture positivity, or blood-culture negativity. The trial was powered to detect an increase of 20% in the risk of failure. This trial was registered at ClinicalTrials.gov, number NCT01421693, and is now closed. Findings Between Sept 18, 2011, and July 14, 2014, we screened 725 patients for eligibility. On July 14, 2014, the trial was stopped early by the data safety and monitoring board because S Typhi

  9. Impact of tiotropium + olodaterol on physical functioning in COPD: results of an open-label observational study

    Directory of Open Access Journals (Sweden)

    Sauer R

    2016-04-01

    Full Text Available Rüdiger Sauer,1 Michaela Hänsel,2 Roland Buhl,3 Roman A Rubin,4 Marcel Frey,5 Thomas Glaab2,3 1Lung Centre Ulm, Ulm, Germany; 2Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany; 3Pulmonary Department, Mainz University Hospital, Mainz, Germany; 4Pulmonary Specialist Practice, Wiesbaden, Germany; 5Biometrics, Alcedis GmbH, Gießen, Germany Background: Maintaining and improving physical functioning is key to mitigating the cycle of deconditioning associated with chronic obstructive pulmonary disease (COPD. We evaluated the impact of free combination of the long-acting anticholinergic tiotropium plus the long-acting β2-agonist olodaterol on physical functioning in a real-world clinical setting. Methods: In this open-label noninterventional study, Global initiative for chronic Obstructive Lung Disease (GOLD B–D patients with COPD aged ≥40 years were treated for 4–6 weeks with either tiotropium 5 µg + olodaterol 5 µg (both via Respimat® inhaler or tiotropium 18 µg (HandiHaler® + olodaterol 5 µg (Respimat® once daily. Physical functioning was assessed by the self-reported 10-item Physical Functioning Questionnaire (PF-10. The primary end point was the percentage of patients achieving therapeutic success, defined as a 10-point increase in the PF-10 between baseline (visit 1 and weeks 4–6 (visit 2. Secondary end points included absolute PF-10 scores, Physicians’ Global Evaluation, satisfaction with Respimat® and adverse events. Results: A total of 1,858 patients were treated: 1,298 (69.9% with tiotropium 5 µg + olodaterol 5 µg and 560 (30.1% with tiotropium 18 µg + olodaterol 5 µg. At study end, 1,683 (92.6% and 1,556 patients (85.6% continued using tiotropium and olodaterol, respectively; 48.9% (95% confidence interval: 46.5, 51.3 achieved the primary end point. Therapeutic success rates were significantly higher for maintenance-naïve patients compared to those who had received prior therapy (59.1% vs 44.5%; P<0

  10. An Open-Label Trial of 12-Week Simeprevir plus Peginterferon/Ribavirin (PR) in Treatment-Naïve Patients with Hepatitis C Virus (HCV) Genotype 1 (GT1)

    Science.gov (United States)

    Asselah, Tarik; Moreno, Christophe; Sarrazin, Christoph; Gschwantler, Michael; Foster, Graham R.; Craxí, Antonio; Buggisch, Peter; Ryan, Robert; Lenz, Oliver; Scott, Jane; Van Dooren, Gino; Lonjon-Domanec, Isabelle; Schlag, Michael; Buti, Maria

    2016-01-01

    Background 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. Methods In this Phase III, open-label study in treatment-naïve HCV GT1 patients with F0–F2 fibrosis, patients with HCV-RNA 12-week regimen. Conclusions 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. Trial Registration ClinicalTrials.gov NCT01846832 PMID:27428331

  11. Effect of treatment with interferon beta-1a on changes in voxel-wise magnetization transfer ratio in normal appearing brain tissue and lesions of patients with relapsing-remitting multiple sclerosis: a 24-week, controlled pilot study.

    Directory of Open Access Journals (Sweden)

    Robert Zivadinov

    Full Text Available This pilot study investigated changes in remyelinating and demyelinating activity in normal appearing brain tissue (NABT and lesions, by using voxel-wise magnetization transfer ratio (VW-MTR, in patients with relapsing-remitting multiple sclerosis (RRMS receiving interferon beta-1a 44 mcg subcutaneously (IFN β-1a SC three times weekly versus healthy controls (HCs (NCT01085318.Increasing (suggestive of remyelination and decreasing (suggestive of demyelination VW-MTR changes in NABT and in T2, T1 and gadolinium (Gd-enhancing lesion volume were measured over 24 weeks in 23 patients treated with IFN β-1a SC and in 15 HCs (where applicable. VW-MTR changes were tested using the Wilcoxon signed-rank or Wilcoxon rank-sum test.A trend for greater volume of NABT with increasing VW-MTR at 24 weeks was observed for patients versus HCs (median [range] 1206 [0-15278]; 342 [0-951] mm3; p = 0.061. NABT volume with increasing VW-MTR at 12 weeks was significantly greater in patients than in HCs (852 [6-11577]; 360 [0-1755] mm3; p = 0.028. Similar findings were detected for lesion volumes. Two patients with notably high numbers of Gd-enhancing lesions at baseline had a markedly greater volume of tissue with increasing VW-MTR compared with other patients. Volume of NABT tissue with decreasing VW-MTR was significantly greater in patients versus HCs at 24 weeks (942 [0-6141]; 297 [0-852] mm3; p<0.001.The significant change in NABT volume with increasing VW-MTR at 12 weeks suggests that active remyelination in patients with RRMS may occur during treatment with IFN β-1a SC. Findings from two patients with the highest number of Gd-enhancing lesions at baseline suggest that extensive remyelination in NABT may occur in patients with high disease activity. Tissue volume with decreasing VW-MTR was greater in patients than in HCs, despite treatment, validating the sensitivity of this technique for detecting MS disease activity.ClinicalTrials.gov NCT01085318.

  12. Congenital multifocal osteomyelitis at 24 weeks' gestation

    International Nuclear Information System (INIS)

    We report an extremely rare case of congenital nonsyphilitic osteomyelitis in a very preterm infant, providing a unique illustration of the radiological appearances at birth, which may serve as a reference to facilitate diagnosis. (orig.)

  13. Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies

    Directory of Open Access Journals (Sweden)

    Ito Mikako

    2011-10-01

    Full Text Available Abstract Background Molecular hydrogen has prominent effects on more than 30 animal models especially of oxidative stress-mediated diseases and inflammatory diseases. In addition, hydrogen effects on humans have been reported in diabetes mellitus type 2, hemodialysis, metabolic syndrome, radiotherapy for liver cancer, and brain stem infarction. Hydrogen effects are ascribed to specific radical-scavenging activities that eliminate hydroxyl radical and peroxynitrite, and also to signal-modulating activities, but the detailed molecular mechanisms still remain elusive. Hydrogen is a safe molecule that is largely produced by intestinal bacteria in rodents and humans, and no adverse effects have been documented. Methods We performed open-label trial of drinking 1.0 liter per day of hydrogen-enriched water for 12 weeks in five patients with progressive muscular dystrophy (PMD, four patients with polymyositis/dermatomyositis (PM/DM, and five patients with mitochondrial myopathies (MM, and measured 18 serum parameters as well as urinary 8-isoprostane every 4 weeks. We next conducted randomized, double-blind, placebo-controlled, crossover trial of 0.5 liter per day of hydrogen-enriched water or placebo water for 8 weeks in 10 patients with DM and 12 patients with MM, and measured 18 serum parameters every 4 weeks. Results In the open-label trial, no objective improvement or worsening of clinical symptoms was observed. We, however, observed significant effects in lactate-to-pyruvate ratios in PMD and MM, fasting blood glucose in PMD, serum matrix metalloproteinase-3 (MMP3 in PM/DM, and serum triglycerides in PM/DM. In the double-blind trial, no objective clinical effects were observed, but a significant improvement was detected in lactate in MM. Lactate-to-pyruvate ratios in MM and MMP3 in DM also exhibited favorable responses but without statistical significance. No adverse effect was observed in either trial except for hypoglycemic episodes in an insulin

  14. Cohort Analysis of a 24-Week Randomized Controlled Trial to Assess the Efficacy of a Novel, Partial Meal Replacement Program Targeting Weight Loss and Risk Factor Reduction in Overweight/Obese Adults

    Directory of Open Access Journals (Sweden)

    Emily Brindal

    2016-05-01

    Full Text Available Our aim was to design and evaluate a weight-loss program, including a partial meal replacement program, point-of-care testing and face-to-face and smartphone app support, appropriate for delivery in a community pharmacy setting. Overweight or obese adults (n = 146, 71.2% female, 48.18 ± 11.75 years old were recruited to participate in a 24-week weight loss study and randomised to two app conditions. The dietary intervention was consistent regardless of app. Twelve weeks of clinic appointments with a trained consultant were followed by only app support for an additional 12 weeks. By week 24, retention was 57.5%. There were no differences between app conditions. Based on a cohort analysis of the trial, the mean decrease in weight from baseline to week 24 was 6.43 ± 1.06 kg for males (p < 0.001 and 5.66 ± 0.70 kg for females (p < 0.001. Mixed models also revealed decreases for LDL Cholesterol (−0.13 ± 0.08 mmol/L, nonsignificant, triglycerides (−0.08 ± 0.05 mmol/L, nonsignificant and an increase in HDL cholesterol (+0.08 ± 0.04 mmol/L, ns were not significant by week 24. Blood glucose (−0.23 ± 0.08 mmol/L, p = 0.040 and blood pressure (Systolic blood pressure −5.77 ± 1.21 Hg/mm, p < 0.001 were significantly lower at week 24 compared to baseline. Weight loss self-efficacy increased and remained significantly higher than baseline at week 24 (16.85 ± 2.93, p < 0.001. Overall, the program supported participants and was successful in achieving significant weight loss and improvements in health outcomes over 24 weeks.

  15. Sustained Virologic Response at 24 Weeks after the End of Treatment Is a Better Predictor for Treatment Outcome in Real-World HCV-Infected Patients Treated by HCV NS3/4A Protease Inhibitors with Peginterferon plus Ribavirin

    Science.gov (United States)

    Kanda, Tatsuo; Nakamoto, Shingo; Sasaki, Reina; Nakamura, Masato; Yasui, Shin; Haga, Yuki; Ogasawara, Sadahisa; Tawada, Akinobu; Arai, Makoto; Mikami, Shigeru; Imazeki, Fumio; Yokosuka, Osamu

    2016-01-01

    Background. Direct-acting antiviral agents against HCV with or without peginterferon plus ribavirin result in higher eradication rates of HCV and shorter treatment duration. We examined which is better for predicting persistent virologic response, the assessment of serum HCV RNA at 12 or 24 weeks after the end of treatment for predicting sustained virologic response (SVR12 or SVR24, respectively) in patients treated by HCV NS3/4A protease inhibitors with peginterferon plus ribavirin. Methods. In all, 149 Japanese patients infected with HCV genotype 1b treated by peginterferon plus ribavirin with telaprevir or simeprevir were retrospectively analyzed: 59 and 90 patients were treated with telaprevir- and simeprevir-including regimens, respectively. HCV RNA was measured by TaqMan HCV Test, version 2.0, real-time PCR assay. SVR12 or SVR24, respectively, was defined as HCV RNA negativity at 12 or 24 weeks after ending treatment. Results. Total SVR rates were 78.0% and 66.7% in the telaprevir and simeprevir groups, respectively. In the telaprevir group, all 46 patients with SVR12 finally achieved SVR24. In the simeprevir group, 60 (93.8%) of the total 64 patients with SVR12 achieved SVR24, with the other 4 patients all being previous-treatment relapsers. Conclusions. SVR12 was suitable for predicting persistent virologic response in almost all cases. In simeprevir-including regimens, SVR12 could not always predict persistent virologic response. Clinicians should use SVR24 for predicting treatment outcome in the use of HCV NS3/4A protease inhibitors with peginterferon plus ribavirin for any group of real-world patients chronically infected with HCV. PMID:27076789

  16. The effect and safety of polylactic acid and adipose-derived stromal vascular fraction cell as an injectable bulking agent in urologic field: a 24-week follow-up study.

    Science.gov (United States)

    Lee, Seong Ho; Ko, Kyungtae; Choo, Min Soo; Lee, Won Ki; Jeong, Hyun Cheol; Cho, Sung Tae; Kim, Sung Yong; Kim, Hayoung; Kang, Won Hwa; Kim, Gun Poong; Yang, Dae Yul

    2015-02-01

    The aim of this study is to evaluate whether polylactic acid (PLA) microspheres and adipose-derived stromal vascular fraction (SVF) cells have appropriate properties as an injectable bulking agent in urologic field. Forty male Sprague-Dawley rats (2-week-old) were randomized into two groups. A total of 0.05 mL of PLA microsphere suspension and 0.05 mL of PLA microsphere suspension mixed with PKH26-labeled SVF cells were injected into bladder wall in group I and group II, respectively. At 2, 8, 16, and 24 weeks of PLA microspheres injection, the volumes of implants were measured and bladder tissues including implants were analyzed and compared grossly and histologically between groups. The distant organs were examined histologically to determine migration of PLA microspheres. At 24 weeks of implantation, 65-70% of injected volume was maintained and there was no significant difference between groups. In histological analyses, injected PLA microspheres were localized in muscular layer of bladder without infiltration into adjacent layer. From 8 to 16 weeks of injection, hybrid tissues contained collagen and actin were observed between PLA microspheres and these findings were more clear in group II. PHK26-labeled SVF cells were identified by fluorescence microscopy at all time points. There was no migration of PLA microspheres to other organs and no abnormality in weight gain and hematologic values. These results suggest the possibility of PLA microspheres as a potentially useful bulking agent in urologic field. And further investigation is needed to know synergic effect of SVF cells.

  17. Omega-3 fatty acids in the management of autism spectrum disorders: findings from an open-label pilot study in Singapore.

    Science.gov (United States)

    Ooi, Y P; Weng, S-J; Jang, L Y; Low, L; Seah, J; Teo, S; Ang, R P; Lim, C G; Liew, A; Fung, D S; Sung, M

    2015-08-01

    The goal of this open-label trial was to examine the efficacy and safety of a 12-week omega-3 fatty acids supplementation among children suffering with Autism Spectrum Disorders (ASD). A total of 41 children and adolescents aged 7-18 years (36 boys, 5 girls; mean age = 11.66, s.d. = 3.05) diagnosed with ASD participated in the study. At post-treatment, participants showed significant improvements on all subscales of the Social Responsiveness Scale (P Omega-3 fatty acids supplementation was well-tolerated and did not cause any serious side effects. Our findings lend some preliminary support for the use of omega-3 fatty acids supplementation in addressing ASD. Future randomized controlled trials of omega-3 fatty acids in ASD with blood fatty acid measurements with a larger sample and longer follow-up period is warranted.

  18. Maintenance of Cognitive Performance and Mood for Individuals with Alzheimer's Disease Following Consumption of a Nutraceutical Formulation: A One-Year, Open-Label Study.

    Science.gov (United States)

    Remington, Ruth; Bechtel, Cynthia; Larsen, David; Samar, Annemarie; Page, Robert; Morrell, Christopher; Shea, Thomas B

    2016-01-01

    Nutritional interventions have shown varied efficacy on cognitive performance during Alzheimer's disease (AD). Twenty-four individuals diagnosed with AD received a nutraceutical formulation (NF: folate, alpha-tocopherol, B12, S-adenosyl methioinine, N-acetyl cysteine, acetyl-L-carnitine) under open-label conditions (ClinicalTrials.gov NCT01320527). Primary outcome was cognitive performance. Secondary outcomes were behavioral and psychological symptoms of dementia (BPSD) and activities of daily living. Participants maintained their baseline cognitive performance and BPSD over 12 months. These findings are consistent with improvement in cognitive performance and BPSD in prior placebo-controlled studies with NF, and contrast with the routine decline for participants receiving placebo.

  19. 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

    2016-01-01

    Objective The purpose of this study was to investigate the efficacy and tolerability of atypical antipsychotics (AAPs) with augmentation by blonanserin in schizophrenic patients. Methods 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. Results The PANSS total score was significantly decreased at 12 weeks of blonanserin augmentation (-21.0±18.1, F=105.849, pschizophrenia who were partially or completely unresponsive to treatment with an AAP.

  20. Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial

    DEFF Research Database (Denmark)

    Bousser, M.G.; Bouthier, J.; Buller, H.R.;

    2008-01-01

    BACKGROUND: Vitamin K antagonists, the current standard treatment for prophylaxis against stroke and systemic embolism in patients with atrial fibrillation, require regular monitoring and dose adjustment; an unmonitored, fixed-dose anticoagulant regimen would be preferable. The aim...... of this randomised, open-label non-inferiority trial was to compare the efficacy and safety of idraparinux with vitamin K antagonists. METHODS: Patients with atrial fibrillation at risk for thromboembolism were randomly assigned to receive either subcutaneous idraparinux (2.5 mg weekly) or adjusted-dose vitamin K...... to treat; the non-inferiority hazard ratio was set at 1.5. This trial is registered with ClinicalTrials.gov, number NCT00070655. FINDINGS: The trial was stopped after randomisation of 4576 patients (2283 to receive idraparinux, 2293 to receive vitamin K antagonists) and a mean follow-up period of 10.7 (SD...

  1. Comparison between IV immune globulin (IVIG) and anti-D globulin for treatment of immune thrombocytopenia: a randomized open-label study.

    Science.gov (United States)

    Eghbali, Aziz; Azadmanesh, Peyman; Bagheri, Bahador; Taherahmadi, Hasan; Sadeghi Sedeh, Bahman

    2016-08-01

    To compare the effect of IV immune globulin (IVIG) and anti-D globulin (anti-D) for treatment of immune thrombocytopenia (ITP) in children. A randomized, open-label, single-center clinical trial was carried out in Amir-Kabir Hospital (Arak, Iran). The study was performed on 60 children with acute and chronic ITP, aged from 1 to 15 years. Patients were randomly assigned (1:1) to 50 μg/kg anti-D or 1 g/kg IVIG. Platelet counting was performed at baseline and at 3, 7, and 14 days after treatment termination. Safety assessment was performed in all patients. Anti-D caused a quicker response on the 3rd day of treatment (P anti-D had lower rate of side effects including fever (P anti-D was associated with rapid rise of platelets compared to IVIG. In addition, anti-D treatment had acceptable safety profile. PMID:26991138

  2. Differential Effects of Acetylcholinesterase Inhibitors on Clinical Responses and Cerebral Blood Flow Changes in Patients with Alzheimer's Disease: A 12-Month, Randomized, and Open-Label Trial

    Directory of Open Access Journals (Sweden)

    Soichiro Shimizu

    2015-04-01

    Full Text Available Background/Aims: The present study evaluated the differences in treatment outcomes and brain perfusion changes among 3 types of acetylcholinesterase inhibitors (AchEIs, i.e. donepezil, rivastigmine, and galantamine. Methods: This was a prospective, longitudinal, randomized, open-label, 3-arm (donepezil, rivastigmine, or galantamine, parallel-group, 12-month clinical trial carried out in 55 patients with AD. Results: At 6 months, the results of the Mini-Mental State Examination (MMSE and the Trail Making Test (TMT-Part A showed an improvement versus baseline in the donepezil treatment group. All groups showed a significant increase in regional cerebral blood flow (rCBF, mainly in the frontal lobe. Significant rCBF reduction was observed in the temporal lobe and cingulate gyrus in all 3 groups. Conclusion: AchEI treatment prevents the progression of cognitive impairment and increases the relative rCBF in the frontal lobe.

  3. An open-label pilot study to assess the effectiveness of krill oil with added vitamins and phytonutrients in the relief of symptoms of PMS

    Directory of Open Access Journals (Sweden)

    Wakeman MP

    2013-09-01

    Full Text Available Michael P Wakeman School of Cancer Sciences, University of Birmingham, Edgbaston, Birmingham, West Midlands, UK Abstract: An open-label pilot study over 4 months to evaluate the effectiveness of a compound formulation of ingredients, which individually have been demonstrated to be implicated in the pathogenesis of premenstrual syndrome to ameliorate the most troublesome symptoms of the condition. The supplement provided thiamine, riboflavin, pyridoxine, vitamin D, soy isoflavones, rosemary extract, and krill oil and was taken each day for the 3 months of the trial. Statistically significant effect was reported by the 29 women who completed the study in relief of anxiety, bloating, mood swings, breast tenderness, skin outbreaks, food cravings, fatigue, forgetfulness, insomnia, and headache after 3 months of treatment compared with baseline. This pilot study indicates the formulation to be effective, and a larger placebo-controlled trial is now planned. Keywords: thiamine, riboflavin, pyridoxine, vitamin D, soy isoflavones, rosemary extract, premenstrual syndrome

  4. Duloxetine for the long-term treatment of Major Depressive Disorder in patients aged 65 and older: an open-label study

    Directory of Open Access Journals (Sweden)

    Watkin John G

    2004-12-01

    Full Text Available Abstract Background Late-life depression is a common, chronic and recurring disorder for which guidelines recommend long-term therapy. The safety and efficacy of duloxetine for the treatment of major depressive disorder (MDD were evaluated using data from elderly patients (age ≥ 65 years; n = 101 who participated in a large, multinational, open-label study. Methods Patients meeting DSM-IV criteria for MDD received duloxetine 80 mg/d (40 mg twice daily (BID to 120 mg/d (60 mg BID for up to 52 weeks. Efficacy measures included the Clinical Global Impression of Severity (CGI-S scale, the 17-item Hamilton Rating Scale for Depression (HAMD17, the Beck Depression Inventory-II (BDI-II, the Patient Global Impression of Improvement (PGI-I scale, and the Sheehan Disability Scale (SDS. Safety and tolerability were evaluated using discontinuation rates, spontaneously reported adverse events, and changes in vital signs, ECG, and laboratory analytes. Results Mean changes in HAMD17 total score at Weeks 6, 28, and 52 were -13.0, -17.4 and -17.5 (all p-values 10% of patients included dizziness, nausea, constipation, somnolence, insomnia, dry mouth, and diarrhea. Most events occurred early in the study. Mean changes at endpoint in blood pressure and body weight were less than 2.0 mm Hg, and -0.1 kg, respectively. Conclusions In this open-label study, duloxetine was effective, safe, and well tolerated in the long-term treatment of MDD in patients aged 65 and older.

  5. Safety and pharmacodynamic effects of a pharmacological chaperone on α-galactosidase A activity and globotriaosylceramide clearance in Fabry disease: report from two phase 2 clinical studies

    Directory of Open Access Journals (Sweden)

    Germain Dominique P

    2012-11-01

    Full Text Available Abstract Background Fabry disease (FD is a genetic disorder resulting from deficiency of the lysosomal enzyme α-galactosidase A (α-Gal A, which leads to globotriaosylceramide (GL-3 accumulation in multiple tissues. We report on the safety and pharmacodynamics of migalastat hydrochloride, an investigational pharmacological chaperone given orally at 150 mg every-other-day. Methods Two open-label uncontrolled phase 2 studies of 12 and 24 weeks (NCT00283959 and NCT00283933 in 9 males with FD were combined. At multiple time points, α-Gal A activity and GL-3 levels were quantified in blood cells, kidney and skin. GL-3 levels were also evaluated through skin and renal histology. Results Compared to baseline, increased α-Gal A activity of at least 50% was demonstrated in blood, skin and kidney in 6 of 9 patients. Patients’ increased α-Gal A activities paralleled the α-Gal A increases observed in vitro in HEK-293 cells transfected with the corresponding mutant form of the enzyme. The same 6 patients who demonstrated increases of α-Gal A activity also had GL-3 reduction in skin, urine and/or kidney, and had α-Gal A mutations that responded in transfected cells incubated with the drug. The 3 patients who did not show a consistent response in vivo had α-Gal A mutations that did not respond to migalastat HCl in transfected cells. Migalastat HCl was well tolerated. Conclusions Migalastat HCl is a candidate pharmacological chaperone that provides a novel genotype-specific treatment for FD. It enhanced α-Gal A activity and resulted in GL-3 substrate decrease in patients with responsive GLA mutations. Phase 3 studies are ongoing. Trial registration Clinicaltrial.gov: NCT00283959 and NCT00283933

  6. Open-label observational study to assess the efficacy and safety of aprepitant for chemotherapy-induced nausea and vomiting prophylaxis in Indian patients receiving chemotherapy with highly emetogenic chemotherapy/moderately emetogenic chemotherapy regimens

    Directory of Open Access Journals (Sweden)

    Hingmire Sachin

    2015-01-01

    Full Text Available Context: Currently, there is limited data on the prevention of chemotherapy-induced nausea and vomiting (CINV in Indian population with aprepitant containing regimens. Aims: The aim was to assess the Efficacy and Safety of Aprepitant for the prevention of nausea and vomiting associated with highly emetogenic chemotherapy/moderately emetogenic chemotherapy (HEC/MEC regimens. Settings and Design: Investigator initiated, multicentric, open-label, prospective, noncomparative, observational trial. Subjects and Methods: Triple drug regimen with aprepitant, palonosetron, and dexamethasaone administration was assessed for the prevention of CINV during acute, delayed, and the overall phase (OP for HEC/MEC Regimens. The primary endpoint was complete response (CR; no emesis and no use of rescue medication and the key secondary endpoint was the complete control (CC; no emesis, no rescue medication and no more than mild nausea during the OP. Statistical Analysis Used: Perprotocol efficacy was analyzed for the first cycle with results represented in terms of CR/CC rates using descriptive statistics. Results: Seventy-five patients were included in the study with median age of 49.7 years and 89.7% being females. The CR rate (OP for patients administered HEC or MEC regimens during the first cycle were 92% and 90.9%, respectively. Similarly, the CC rates (OP were 75% and 90% for these regimens, respectively. 7 (9.2% patients reported adverse drug reactions that were mild and transient with no reports of any serious adverse events. Conclusions: Use of aprepitant containing regimen for patients receiving HEC/MEC regimen resulted in significantly high CR and CC response rates, which further consolidate its potential role to improve patient quality of life and compliance to disease management.

  7. 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. PMID:25471318

  8. An open label prospective randomized trial to compare the efficacy of coal tar-salicylic acid ointment versus calcipotriol/betamethasone dipropionate ointment in the treatment of limited chronic plaque psoriasis

    Directory of Open Access Journals (Sweden)

    Sujay Khandpur

    2014-01-01

    Full Text Available Background: Chronic plaque psoriasis is a common papulosquamous skin disorder, for which a number of topical agents are being used including coal tar, topical steroids and more recently topical calcipotriol/betamethasone dipropionate. There is no study comparing purified coal tar preparation with calcipotriol/betamethasone dipropionate ointment in limited chronic plaque psoriasis. Aims and Objectives: A prospective randomized open label controlled trial to compare the efficacy and safety of topical application of coal tar-salicylic acid ointment with calcipotriol/betamethasone dipropionate ointment applied once at night for 12 weeks for the treatment of limited chronic plaque psoriasis. Materials and Methods: A total of 62 patients of limited chronic plaque psoriasis (body surface area <10% were randomized into two treatment groups: Group A received topical application of 6% coal tar with 3% salicylic acid ointment and Group B received calcipotriol/betamethasone dipropionate, once at night for 12 weeks. Results were assessed based on psoriasis area severity index (PASI scores and patient global assessment (PGA at each visit. Results: Mean PASI was significantly lower at week 2 (P = 0.01 and week 4 follow-up (P = 0.05 and the mean reduction in PASI was significantly higher at week 2 (P = 0.02 with calcipotriol/betamethasone than coal tar-salicylic acid, but this difference was not sustained at subsequent follow-up visits. Similarly, PGA scores at weeks 2 and 4 were significantly lower with calcipotriol/betamethasone dipropionate ointment (P = 0.003 and P = 0.007 respectively. There was no significant difference in any parameter during subsequent follow-up visits or at the end of the treatment phase (12 weeks. Conclusion: Topical nightly application of calcipotriol/betamethasone dipropionate ointment leads to an initial, more rapid reduction in disease severity, but the overall outcome parameters are comparable in the two treatment groups.

  9. Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial

    Science.gov (United States)

    Todd, John A.; Porter, Linsey; Smyth, Deborah J.; Rainbow, Daniel B.; Ferreira, Ricardo C.; Yang, Jennie H.; Bell, Charles J. M.; Schuilenburg, Helen; Challis, Ben; Clarke, Pamela; Coleman, Gillian; Dawson, Sarah; Goymer, Donna; Kennet, Jane; Brown, Judy; Greatorex, Jane; Goodfellow, Ian; Evans, Mark; Mander, Adrian P.; Bond, Simon; Wicker, Linda S.

    2016-01-01

    Background Interleukin-2 (IL-2) has an essential role in the expansion and function of CD4+ regulatory T cells (Tregs). Tregs reduce tissue damage by limiting the immune response following infection and regulate autoreactive CD4+ effector T cells (Teffs) to prevent autoimmune diseases, such as type 1 diabetes (T1D). Genetic susceptibility to T1D causes alterations in the IL-2 pathway, a finding that supports Tregs as a cellular therapeutic target. Aldesleukin (Proleukin; recombinant human IL-2), which is administered at high doses to activate the immune system in cancer immunotherapy, is now being repositioned to treat inflammatory and autoimmune disorders at lower doses by targeting Tregs. Methods and Findings To define the aldesleukin dose response for Tregs and to find doses that increase Tregs physiologically for treatment of T1D, a statistical and systematic approach was taken by analysing the pharmacokinetics and pharmacodynamics of single doses of subcutaneous aldesleukin in the Adaptive Study of IL-2 Dose on Regulatory T Cells in Type 1 Diabetes (DILT1D), a single centre, non-randomised, open label, adaptive dose-finding trial with 40 adult participants with recently diagnosed T1D. The primary endpoint was the maximum percentage increase in Tregs (defined as CD3+CD4+CD25highCD127low) from the baseline frequency in each participant measured over the 7 d following treatment. There was an initial learning phase with five pairs of participants, each pair receiving one of five pre-assigned single doses from 0.04 × 106 to 1.5 × 106 IU/m2, in order to model the dose-response curve. Results from each participant were then incorporated into interim statistical modelling to target the two doses most likely to induce 10% and 20% increases in Treg frequencies. Primary analysis of the evaluable population (n = 39) found that the optimal doses of aldesleukin to induce 10% and 20% increases in Tregs were 0.101 × 106 IU/m2 (standard error [SE] = 0.078, 95% CI = −0

  10. 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...

  11. Comparison of oral psoralen-UV-A with a portable tanning unit at home vs hospital-administered bath psoralen-UV-A in patients with chronic hand eczema - An open-label randomized controlled trial of efficacy

    NARCIS (Netherlands)

    van Coevorden, AM; Kamphof, WG; van Sonderen, E; Bruynzeel, DP; Coenraads, PJ

    2004-01-01

    Objective: To study whether oral psoralen-UV-A (PUVA) with a portable tanning unit at home is as effective as hospital-administered bath PUVA in patients with chronic hand eczema. Design: Open-label randomized controlled trial, with a 10-week treatment period and an 8-week follow-up period. Setting:

  12. 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

  13. A 24-Week, Randomized, Controlled Study to Evaluate the Tolerability, Safety and Efficacy of 2 Different Titration Schemes of the Rivastigmine Patch in Japanese Patients with Mild to Moderate Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Yu Nakamura

    2015-09-01

    Full Text Available Aim: To investigate whether 1-step titration of the rivastigmine patch (initiated at 5 cm2 and titrated to 10 cm2 after 4 weeks is well tolerated in Japanese patients with Alzheimer's disease (AD as compared to 3-step titration (initiated at 2.5 cm2 and titrated by 2.5 cm2 every 4 weeks to 10 cm2. Methods: A 24-week, multicenter, randomized, double-blind study was conducted in Japan between July 2012 and May 2014. Patients with mild to moderate AD aged 50-85 years were randomized 1:1 to 1-step or 3-step titration of the rivastigmine once-daily patch. The primary endpoint was the proportion of patients with adverse events leading to discontinuation. Results: Of 216 patients randomized, 215 (1-step, n = 107; 3-step, n = 108 were included in the safety analysis. The primary endpoint outcome was 15.0% in the 1-step group and 18.5% in the 3-step group. The observed treatment difference was −3.6% (95% confidence interval: −17.0, 9.6, falling within the prespecified acceptance range. Conclusion: The tolerability of two different titration schemes was similar in Japanese patients with AD.

  14. Effects of 24-week Tai Chi Exercise on the Static Postural Balance of the Elder Persons%24周太极拳锻炼对中老年人静态平衡功能的影响

    Institute of Scientific and Technical Information of China (English)

    虞定海; 王三; 杨慧馨; 斑玉生

    2011-01-01

    Objective To explore the effects of 24-week Tai Chi exercise on the static balance of elder persons. Methods Seventy subjects, aged 55-65 years, who took part in simplified Tai chi or 42-style Tai chi exercises, were enrolled in this study. They practiced Tai Chi Quan 60 minutes per day, 4 days per week for 24 weeks. Their static balance parameters, including TL (total length of swinging path way) , area (area of swinging of pathway) , and other were measured under double feet standing with eyes opened and closed, and single foot standing with eyes opened and closed using WIN-POD System before and after the practice. Results After 24 weeks practice, (1) for male subjects, TL, area, X speed, X deviation and Y deviation under double feet standing with eyes opened, and TL, area and Avg.v (average velocity) under double feet standing with eyes closed decreased significantly, as compared with that before practice (P<0.05) ; for female subjects, Y speed decreased significantly under double feet standing with eyes opened (P < 0.05) , as compared with that before the practice; (2) For male subjects, under single foot standing with eyes opened, there are significant differences in TL and Avg.v after experiment (P < 0.05 and P < 0.01) and X speed decreased significantly (P<0.01) under single foot standing with eyes opened (P<0.01) .For female subjects, there were significant decreases in area, X deviation, Y deviation (P < 0.05) and X speed (P<0.01) , while increase in L/A (ratio ofTL and area) (P<0.05) after the experiment. Conclusion 24-week Tai Chi practice has positive impact on the static balance capacity of elder persons.%目的:探讨24周太极拳锻炼对中老年人静态平衡机能的影响.方法:24周简化太极拳和42式太极拳锻炼(每周锻炼4次,每次60分钟)前后,55~65岁中老年人70名分别在双足睁眼、闭眼,单足睁眼、闭眼状态下,采用WIN-POD平衡功能检测系统测试重心动摇总轨迹长(TL)、外周面积(Area)、

  15. Prospective, naturalistic study of open-label OROS methylphenidate treatment in Chinese school-aged children with attention-deficit/hyperactivity disorder

    Institute of Scientific and Technical Information of China (English)

    ZHENG Yi; GONG Mei-en; YIN Qing-yun; MAI Jian-ning; JING Jin; LUO Xiang-yang; MA Hong-wei; LI Hai-bo; XIE Ling; LI Yan; Kuang Gui-fang; WANG Yu-feng; YI Ming-ji; WANG Feng; ZHU Xiao-hua; YAO Yah-bin; QIN Jiong; WANG Li-wen; ZOU Li-ping; JIN Xing-ming; XU Tong; WANG Yi; QI Yuan-li

    2011-01-01

    Background Attention deficit hyperactivity disorder (ADHD) is one of the most common mental disorders during childhood,characterized by the core symptoms of hyperactivity,impulsivity and inattention and puts great burden on children themselves,their families and the society.Osmotic release oral system methylphenidate (OROS-MPH) is a once-daily controlled-release formulation developed to overcome some of the limitations associated with immediate-release methylphenidate (IR-MPH).It has been marketed in China since 2005 but still lacks data from large-sample clinical trials on efficacy and safety profiles.The aim of this study was to evaluate the effectiveness and safety of OROS-MPH in children aged 6 to 16 years with ADHD under naturalistic clinical setting.Methods This 6-week,multi-center,prospective,open-label study enrolled 1447 ADHD children to once-daily OROS-MPH (18 mg,36 mg or 54 mg) treatment.The effectiveness measures were parent-rated Inattention and Overactivity With Aggression (IOWA) Conners I/O and O/D subscales,physician-rated CGI-I and parent-rated global efficacy assessment scale.Blood pressure,pulse rate measurement,adverse events (AEs) and concomitant medications and treatment review were conducted by the investigator and were served as safety measures.Results A total of 1447 children with ADHD (mean age (9.52±2.36) years) were enrolled in this trial.Totally 96.8%children received an OROS-MPH modal dose of 18 mg,3.1% with 36 mg and 0.1% with 54 mg at the endpoint of study.The parent IOWA Conners I/O score at the end of week 2 showed statistically significant (P <0.001) improvement with OROS-MPH (mean:6.95±2.71) versus the score at baseline (10.45±2.72).The change in the parent IOWA Conners O/D subscale,CGI-I and parent-rated global efficacy assessment scale also supported the superior efficacy for OROS-MPH treatment.Fewer than half of 1447 patients (511 (35.3%)) reported AEs,and the majority of the events reported were mild (68.2

  16. 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

    Directory of Open Access Journals (Sweden)

    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.

  17. Augmentation of antipsychotics with glycine may ameliorate depressive and extrapyramidal symptoms in schizophrenic patients – a preliminary 10-week open-label study

    Directory of Open Access Journals (Sweden)

    Strzelecki, Dominik

    2013-07-01

    Full Text Available Aim. The objective of this study was to analyze the changes in depressive and extrapyramidal symptomatology during glycine augmentation of antipsychotic treatment in patients with schizophrenia.Materials and methods. Twenty-nine schizophrenic patients (ICD-10 with predominant negative symptoms in stable mental state participated in a 10-week open-label prospective study. Patients received stable doses of antipsychotic drugs for at least 3 months before glycine application. During the next 6 weeks patients received augmentation of antipsychotic treatment with glycine (up to 60 g per day. The first and last two weeks of observation were used to assess stability of mental state. Symptom severity was assessed using the Hamilton Depression Rating Scale (HDRS, the Positive and Negative Syndrome Scale (PANSS, and the Simpson-Angus Extrapyramidal Symptom Rating Scale (SASResults. In the studied group after 6 weeks of administration of glycine a significant improvement in depressive symptoms (reduced scores by 25.8% in HDRS, p <0.001 and reduced scoring in mood symptoms of PANSS were observed. In SAS a reduction of extrapyramidal symptoms’ severity (p <0.05 was also noted. Two weeks after the glycine augmentation the symptom severity in the HDRS, PANSS, and SAS remained at similar levels.Conclusions. Glycine augmentation of antipsychotic treatment may reduce the severity of depressive and extrapyramidal symptoms. Glycine use was safe and well tolerated.

  18. Clinical outcomes of HER2-positive metastatic breast cancer patients with brain metastasis treated with lapatinib and capecitabine: an open-label expanded access study in Korea

    Directory of Open Access Journals (Sweden)

    Ro Jungsil

    2012-07-01

    Full Text Available Abstract Background To evaluate efficacy in patients with brain metastasis (BM on entry into the lapatinib expanded access program (LEAP. Methods LEAP is a worldwide, single-arm, open-label study. HER2-positive, locally-advanced or metastatic breast cancer patients with progression after an anthracycline, taxane, and trastuzumab were eligible. Patients received capecitabine 2000 mg/m2 daily in two divided doses, days 1–14, every 21 days and lapatinib 1250 mg once daily. Results Among 186 patients enrolled in 6 Korean centers, 58 had BM. Progression-free survival (PFS was 18.7 weeks in patients with BM and 19.4 weeks without BM (P = 0.88. In patients with BM, brain response was synchronized with systemic responses (P = 0.0001. Overall survival (OS was 48.9 weeks in patients with BM and 64.6 weeks without BM (P = 0.23. Multivariable analysis found hormone receptor positivity (P = 0.003 and clinical benefit rate (CBR of combined systemic and brain disease (P  Conclusion Lapatinib plus capecitabine is equally effective in patients with or without BM. Trial registration ClinicalTrials.gov (NCT00338247

  19. A randomized, open-label, multicentre study to evaluate plasma atherosclerotic biomarkers in patients with type 2 diabetes mellitus and arteriosclerosis obliterans when treated with Probucol and Cilostazol

    Institute of Scientific and Technical Information of China (English)

    Xiao-Wei Ma; Xiao-Hui Guo; Xin-Hua Xiao; Li-Xin Guo; Xiao-Feng Lv; Quan-Min Li; Yan Gao

    2012-01-01

    Objectives To evaluate the plasma atherosclerotic biomarkers in patients with type 2 diabetes mellitus (T2DM) and arteriosclerosis obliteran (ASO) when treated with Probucol plus Cilostazol in combination and individually. Methods In this open-label study, patients aged 40-75 years were randomized to receive conventional therapy alone, or with Cilostazol 100 mg bid, or with Probucol 250 mg bid, or with both in combination. Endpoints included changes in plasma biomarker and safety at 12 weeks. Results Of the 200 randomized patients, 165 for per-protocol and 160 for the safety (QTc intervals) were set, respectively. Probucol significantly reduced total cholesterol (P < 0.001), low-density lipoprotein cholesterol (LDL-C), (P = 0.01), and high-density lipoprotein cholesterol (HDL-C) (P < 0.001) compared with conventional therapy. Cilostazol was effective in increasing HDL-C (P = 0.002) and reducing triglycerides levels (P < 0.01) compared with conventional therapy. A trend towards significance was observed for the difference between conventional therapy alone and Probucol plus Cilostazol group for the change in oxidized low-density lipoprotein (Ox-LDL, P = 0.065). No significant effects on the majority of the remaining biomarkers were found across the treatment groups. Conclusions We have confirmed that Ox-LDL could be a possible plasma atherosclerotic biomarker among the evaluated biomarkers, which reflected the synergetic effect of Cilostazol plus Probucol in patients with T2DM and ASO shown previously in preclinical studies.

  20. 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

    Directory of Open Access Journals (Sweden)

    Mangesh Bhalerao

    2013-06-01

    Full Text Available 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 tolerability were analysed from the following grades by patients and confirmed by doctor. Of 50 patients, 63% were diagnosed with cough due to upper respiratory tract infections, 17% common cold, 12% allergic cough and 8% smoker’s cough. Substantial improvement, i.e., excellent to good response, in relief of cough was noted in 42 (84% out of 50 patients and fair response in another 4 (8%. Only 4 out of 50 patients showed no relief in symptoms. Most of the patients (98% accepted the remedy well. Only one adverse event was reported. However, a relation to the medication was classified to be unlikely. The test drug Mykoff® is an effective and safe cough syrup that is highly acceptable for patients with cough of short duration.

  1. Combined treatment with low-dose cyclosporine and calcipotriol/betamethasone dipropionate ointment for moderate-to-severe plaque psoriasis: a randomized controlled open-label study.

    Science.gov (United States)

    Vena, Gino A; Galluccio, Antonia; Pezza, Michele; Vestita, Michelangelo; Cassano, Nicoletta

    2012-08-01

    Combination therapy is a common approach to psoriasis, aimed at improving clinical response and minimizing the risk of side effects. The aim of this pilot randomized open-label study was to evaluate the efficacy and safety of the combination of low-dose cyclosporine (CsA) with calcipotriol-betamethasone dipropionate (CBD) ointment in the treatment of psoriasis. Sixty patients with moderate-to-severe plaque psoriasis were randomized to receive CsA, 2 mg/kg/day, combined with CBD ointment (n = 30) or CsA, at the same daily dosage, in combination with an emollient (n = 30), for 8 weeks. The primary efficacy parameter was the Psoriasis Area and Severity Index (PASI) 75 response rate at 8 weeks. Combination therapy with CsA and CBD ointment was more effective than CsA and emollient treatment, with statistically significant results, particularly less itching after 4 and 8 weeks and PASI reduction at all post-baseline visits. Significantly more patients treated with CsA + CBD achieved the PASI 75 at 8th week (87% vs 37% in the CsA-emollient group; p = 0.0001). The efficacy results were paralleled by the investigator and patient's global assessment of disease severity at the end of study. Our results suggest that the addition of CBD ointment to low-dose CsA enhances clinical response and improves the risk/benefit ratio. PMID:21756153

  2. Noninterventional Open-Label Trial Investigating the Efficacy and Safety of Ectoine Containing Nasal Spray in Comparison with Beclomethasone Nasal Spray in Patients with Allergic Rhinitis

    Directory of Open Access Journals (Sweden)

    Uwe Sonnemann

    2014-01-01

    Full Text Available Objectives. The current study aimed to compare the efficacy and safety of a classical anti-inflammatory beclomethasone nasal spray in comparison to a physic-chemical stabilizing ectoine containing nasal spray in the treatment of allergic rhinitis. Design and Methods. This was a noninterventional, open-label, observational trial investigating the effects of beclomethasone or ectoine nasal spray on nasal symptoms and quality of life. Over a period of 14 days, patients were asked to daily document their symptoms. Efficacy and tolerability were assessed by both physicians and patients. Results. Both treatments resulted in a significant decrease of TNSS values. An equivalence test could not confirm the noninferiority of ectoine treatment in comparison with beclomethasone treatment. Although clear symptom reduction was achieved with the ectoine products, the efficacy judgment showed possible advantages for the beclomethasone group. Importantly, tolerability results were comparably good in both groups, and a very low number of adverse events supported this observation. Both treatments resulted in a clear improvement in the quality of life as assessed by a questionnaire answered at the beginning and at the end of the trial. Conclusion. Taken together, it was shown that allergic rhinitis can be safely and successfully treated with beclomethasone and also efficacy and safety were shown for ectoine nasal spray.

  3. Omega-3 fatty acids in the management of autism spectrum disorders: findings from an open-label pilot study in Singapore.

    Science.gov (United States)

    Ooi, Y P; Weng, S-J; Jang, L Y; Low, L; Seah, J; Teo, S; Ang, R P; Lim, C G; Liew, A; Fung, D S; Sung, M

    2015-08-01

    The goal of this open-label trial was to examine the efficacy and safety of a 12-week omega-3 fatty acids supplementation among children suffering with Autism Spectrum Disorders (ASD). A total of 41 children and adolescents aged 7-18 years (36 boys, 5 girls; mean age = 11.66, s.d. = 3.05) diagnosed with ASD participated in the study. At post-treatment, participants showed significant improvements on all subscales of the Social Responsiveness Scale (P < 0.01) and the Social and Attention Problems syndrome scales of the Child Behavior Checklist (P < 0.05). Blood fatty acid levels were significantly correlated with changes in the core symptoms of ASD. Baseline levels of blood fatty acid levels were also predictive of response to the omega-3 treatment. Omega-3 fatty acids supplementation was well-tolerated and did not cause any serious side effects. Our findings lend some preliminary support for the use of omega-3 fatty acids supplementation in addressing ASD. Future randomized controlled trials of omega-3 fatty acids in ASD with blood fatty acid measurements with a larger sample and longer follow-up period is warranted. PMID:25804268

  4. The effects of orally administered Beta-glucan on innate immune responses in humans, a randomized open-label intervention pilot-study.

    Directory of Open Access Journals (Sweden)

    Jenneke Leentjens

    Full Text Available RATIONALE: To prevent or combat infection, increasing the effectiveness of the immune response is highly desirable, especially in case of compromised immune system function. However, immunostimulatory therapies are scarce, expensive, and often have unwanted side-effects. β-glucans have been shown to exert immunostimulatory effects in vitro and in vivo in experimental animal models. Oral β-glucan is inexpensive and well-tolerated, and therefore may represent a promising immunostimulatory compound for human use. METHODS: We performed a randomized open-label intervention pilot-study in 15 healthy male volunteers. Subjects were randomized to either the β -glucan (n = 10 or the control group (n = 5. Subjects in the β-glucan group ingested β-glucan 1000 mg once daily for 7 days. Blood was sampled at various time-points to determine β-glucan serum levels, perform ex vivo stimulation of leukocytes, and analyze microbicidal activity. RESULTS: β-glucan was barely detectable in serum of volunteers at all time-points. Furthermore, neither cytokine production nor microbicidal activity of leukocytes were affected by orally administered β-glucan. CONCLUSION: The present study does not support the use of oral β-glucan to enhance innate immune responses in humans. TRIAL REGISTRATION: ClinicalTrials.gov NCT01727895.

  5. Effect of osmotic-release oral system methylphenidate on learning skills in adolescents with attention-deficit/hyperactivity disorder: an open-label study.

    Science.gov (United States)

    Na, Kyoung-Sae; Lee, Soyoung Irene; Hong, Sungdo David; Kim, Ji-Hoon; Shim, Se-Hoon; Choi, Jeewook; Yang, Jaewon; Lee, Moon-Soo; Joung, Yoo-Sook; Kim, Eui-Jung; Park, Joon-Ho

    2013-07-01

    We evaluated the effect of osmotic-release oral system (OROS) methylphenidate on learning skills in adolescents with attention-deficit/hyperactivity disorder (ADHD). In an open-label study, 121 adolescents with ADHD were administered flexible doses of OROS methylphenidate for 12 weeks. The efficacy of methylphenidate on ADHD symptoms was evaluated by ADHD Rating Scale (ARS) and Clinical Global Impression Scale (CGI). Learning Skills Test (LST) was used to measure the learning skills of the participants at the baseline and the endpoint. Continuous performance test, visuospatial and verbal working memory, verbal fluency, and inhibition were evaluated before and after the 12 weeks of treatment. The mean total and subscores of LST were significantly increased after the 12-week treatment with OROS methylphenidate. Executive functions were also improved during the trial, with the exception of inhibition measured by the Stroop Test. To the best of our knowledge, this is the first study to examine the influence of OROS methylphenidate on learning skill. As a result, OROS methylphenidate was effective in enhancing learning skills in adolescents with ADHD.

  6. 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.

  7. A Prospective Open-Label Trial of Memantine Hydrochloride for the Treatment of Social Deficits in Intellectually Capable Adults With Autism Spectrum Disorder.

    Science.gov (United States)

    Joshi, Gagan; Wozniak, Janet; Faraone, Stephen V; Fried, Ronna; Chan, James; Furtak, Stephannie; Grimsley, Emily; Conroy, Kristina; Kilcullen, J Ryan; Woodworth, K Yvonne; Biederman, Joseph

    2016-06-01

    This prospective 12-week open-label trial evaluates the tolerability and efficacy of memantine hydrochloride for the treatment of core social and cognitive deficits in adults with high-functioning autism spectrum disorder (ASD). Measures for assessment of therapeutic response included the Social Responsiveness Scale-Adult Research Version (SRS-A), disorder-specific Clinical Global Impression scales, Behavior Rating Inventory of Executive Functioning-Adult Self-Report, Diagnostic Analysis of Nonverbal Accuracy Scale, and Cambridge Neuropsychological Test Automated Battery. Eighteen adults (mean age, 28 ± 9.5 years) with high-functioning ASD (SRS-A raw score, 99 ± 17) were treated with memantine (mean dose, 19.7 ± 1.2 mg/d; range, 15-20 mg), and 17 (94%) completed the trial. Treatment with memantine was associated with significant reduction on informant-rated (SRS-A, -28 ± 25; P nonverbal communication on the Diagnostic Analysis of Nonverbal Accuracy Scale test and in executive function per self-report (Behavior Rating Inventory of Executive Functioning-Adult Self-Report Global Executive Composite, -6 ± 8.8; P < 0.015) and neuropsychological assessments (Cambridge Neuropsychological Test Automated Battery). Memantine treatment was generally well tolerated and was not associated with any serious adverse events. Treatment with memantine appears to be beneficial for the treatment of ASD and associated psychopathology and cognitive dysfunction in intellectually capable adults. Future placebo-controlled trials are warranted. PMID:27043118

  8. Average bioequivalence of single 500 mg doses of two oral formulations of levofloxacin: a randomized, open-label, two-period crossover study in healthy adult Brazilian volunteers

    Directory of Open Access Journals (Sweden)

    Eunice Kazue Kano

    2015-03-01

    Full Text Available Average bioequivalence of two 500 mg levofloxacin formulations available in Brazil, Tavanic(c (Sanofi-Aventis Farmacêutica Ltda, Brazil, reference product and Levaquin(c (Janssen-Cilag Farmacêutica Ltda, Brazil, test product was evaluated by means of a randomized, open-label, 2-way crossover study performed in 26 healthy Brazilian volunteers under fasting conditions. A single dose of 500 mg levofloxacin tablets was orally administered, and blood samples were collected over a period of 48 hours. Levofloxacin plasmatic concentrations were determined using a validated HPLC method. Pharmacokinetic parameters Cmax, Tmax, Kel, T1/2el, AUC0-t and AUC0-inf were calculated using noncompartmental analysis. Bioequivalence was determined by calculating 90% confidence intervals (90% CI for the ratio of Cmax, AUC0-t and AUC0-inf values for test and reference products, using logarithmic transformed data. Tolerability was assessed by monitoring vital signs and laboratory analysis results, by subject interviews and by spontaneous report of adverse events. 90% CIs for Cmax, AUC0-t and AUC0-inf were 92.1% - 108.2%, 90.7% - 98.0%, and 94.8% - 100.0%, respectively. Observed adverse events were nausea and headache. It was concluded that Tavanic(c and Levaquin(c are bioequivalent, since 90% CIs are within the 80% - 125% interval proposed by regulatory agencies.

  9. Recent Ⅳ-drug users with chronic hepatitis C can be efficiently treated with daily high dose induction therapy using consensus interferon: An open-label pilot study

    Institute of Scientific and Technical Information of China (English)

    Th Witthoeft; M Fuchs; D Ludwig

    2007-01-01

    AIM: To investigate the use of high dose consensusinterferon in combination with ribavirin in former iv drug users infected with hepatitis C.METHODS: We started, before pegylated (PEG)interferons were available, an open-label study to investigate the efficacy and tolerability of high dose induction therapy with consensus interferon (CIFN) and ribavirin in treatment of naiive patients with chronic hepatitis C. Fifty-eight patients who were former iv drug users, were enrolled receiving 18 μg of CIFN daily for 8 wk, followed by 9 μg daily for up to wk 24 or 48 and 800 mg of ribavirin daily. End point of the study was tolerability and eradication of the virus at wk 48 and sustained virological response at wk 72.RESULTS: More than 62% of patients responded to the treatment with CIFN at wk 24 or 48, respectively,showing a negative qualitative PCR [genotype 1 fourteen patients (56%), genotype 2 five (50%),genotype 3 thirteen (87%), genotype 4 four (50%)].Forty-eight percent of genotype 1 patients showed sustained virological response (SVR) six months after the treatment.CONCLUSION: CIFN on a daily basis is well tolerated and side effects like leuko- and thrombocytopenia are moderate. End of therapy (EOT) rates are slightly lower than the newer standard therapy with pegylated interferons. CIFN on a daily basis might be a favourable therapy regimen for patients with GT1 and high viral load or for non-responders after failure of standard therapy.

  10. A Complex Multiherbal Regimen Based on Ayurveda Medicine for the Management of Hepatic Cirrhosis Complicated by Ascites: Nonrandomized, Uncontrolled, Single Group, Open-Label Observational Clinical Study

    Directory of Open Access Journals (Sweden)

    Manish V. Patel

    2015-01-01

    Full Text Available Hepatic cirrhosis is one of the leading causes of death worldwide, especially if complicated by ascites. This chronic condition can be related to the classical disease entity jalodara in Traditional Indian Medicine (Ayurveda. The present paper aims to evaluate the general potential of Ayurvedic therapy for overall clinical outcomes in hepatic cirrhosis complicated by ascites (HCcA. In form of a nonrandomized, uncontrolled, single group, open-label observational clinical study, 56 patients fulfilling standardized diagnostic criteria for HCcA were observed during their treatment at the P. D. Patel Ayurveda Hospital, Nadiad, India. Based on Ayurvedic tradition, a standardized treatment protocol was developed and implemented, consisting of oral administration of single and compound herbal preparations combined with purificatory measures as well as dietary and lifestyle regimens. The outcomes were assessed by measuring liver functions through specific clinical features and laboratory parameters and by evaluating the Child-Pugh prognostic grade score. After 6 weeks of treatment and a follow-up period of 18 weeks, the outcomes showed statistically significant and clinically relevant improvements. Further larger and randomized trials on effectiveness, safety, and quality of the Ayurvedic approach in the treatment of HCcA are warranted to support these preliminary findings.

  11. Efficacy and long term safety of alipogene tiparvovec (AAV1-LPLS447X) gene therapy for lipoprotein lipase deficiency: an open label trial

    Science.gov (United States)

    Gaudet, Daniel; Méthot, Julie; Déry, Stéphane; Brisson, Diane; Essiembre, Christiane; Tremblay, Gérald; Tremblay, Karine; de Wal, Janneke; Twisk, Jaap; van den Bulk, Nick; Sier-Ferreira, Valerie; van Deventer, Sander

    2016-01-01

    We describe the 2-year follow-up of an open-label trial (CT-AMT-011-01) of AAV1-LPLS447X gene therapy for lipoprotein lipase deficiency (LPLD), an orphan disease associated with chylomicronemia, severe hypertriglyceridemia, metabolic complications and potentially life-threatening pancreatitis. The LPL S447X gene variant, in an adeno-associated viral vector of serotype 1 (alipogene tiparvovec), was administered to 14 adult LPLD patients with a prior history of pancreatitis. Primary objectives were to assess the long-term safety of alipogene tiparvovec and achieve a ≥40% reduction in fasting median plasma triglyceride (TG) at 3–12 weeks compared with baseline. Cohorts 1 (n=2) and 2 (n=4) received 3 × 1011gc/kg, and cohort 3 (n=8) received 1 × 1012gc/kg. Cohorts 2 and 3 also received immunosuppressants from the time of alipogene tiparvovec administration and continued for 12 weeks. Alipogene tiparvovec was well tolerated, without emerging safety concerns for 2 years. Half of the patients demonstrated a ≥40% reduction in fasting TG between 3–12 weeks. TG subsequently returned to baseline, although sustained LPL S447X expression and long-term changes in TG-rich lipoprotein characteristics were noted independently of the effect on fasting plasma TG. PMID:22717743

  12. The efficacy and safety of cyclosporine reduction in de novo renal allograft patients receiving sirolimus and corticosteroids: results from an open-label comparative study.

    Science.gov (United States)

    Mühlbacher, Ferdinand; Neumayer, Hans-Helmut; del Castillo, Domingo; Stefoni, Sergio; Zygmunt, Anthony J; Budde, Klemens

    2014-02-01

    This study evaluated the safety and efficacy of a sirolimus, corticosteroid, and cyclosporine reduction regimen in an open-label, 12-month trial of 420 de novo renal allograft recipients at 49 European transplant centers. One month post-transplantation, 357 patients were randomized to receive standard-dose cyclosporine (sCsA, n = 179) or reduced-dose cyclosporine (rCsA, n = 178). All patients also received sirolimus and corticosteroids. The primary end points were the rate of biopsy-confirmed acute rejection (BCAR) and renal function, as measured by serum creatinine. Baseline demographic and donor characteristics were similar between groups. BCAR rates at 12 months were not significantly different: 11.2% for rCsA patients and 16.2% for sCsA patients. Mean serum creatinine (±SEM) was significantly lower (1.75 ± 0.10 vs. 1.97 ± 0.07 mg/dl, P renal allograft recipients. Sirolimus administered with rCsA and corticosteroids provided adequate immunosuppression while reducing the potential for the nephrotoxic effects of cyclosporine. These findings may help to improve long-term renal allograft outcomes.

  13. The Effect of a Phaseolus vulgaris and Dietary Fiber Based Supplement on Advanced Glycation End Products: An Open-label Trial

    Directory of Open Access Journals (Sweden)

    Brett J. West

    2015-07-01

    Full Text Available Elevated Advanced Glycation End product (AGE levels are associated with certain impaired health states. As these are disruptive to the function of healthy tissues, due to their protein cross-linking ability, AGEs are significant contributors to the aging process. In fact, population studies have revealed that AGE levels tend to increase as we get older. Certain lifestyle and dietary factors may accelerate AGE accumulation. Therefore, strategies intended to modify these factors, or mitigate their effects, may be useful in controlling the aging process. In an 11 week open-label clinical trial, 30 adult volunteers consumed daily a commercially available combination of white kidney bean extract, dietary fibers, &beta-carotene and noni (Morinda citrifolia fruit pulp, in combination with calorie restriction and exercise. During the course of the trial, participants experienced significant weekly declines in average body weight and fat mass. The average AGE score, as measured by skin auto-fluorescence, had also decreased significantly. In terms of AGE associated years, the change in AGE scores corresponded to an average decrease of 8.83 years. The results indicate that the intervention contributed to improved health and exhibited anti-aging properties.

  14. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial

    DEFF Research Database (Denmark)

    Home, Philip D; Pocock, Stuart J; Beck-Nielsen, Henning;

    2009-01-01

    with the combination of the two over 5-7 years of follow-up. We also assessed comparative safety. METHODS: In a multicentre, open-label trial, 4447 patients with type 2 diabetes on metformin or sulfonylurea monotherapy with mean haemoglobin A(1c) (HbA(1c)) of 7.9% were randomly assigned to addition of rosiglitazone (n.......80-1.63) for myocardial infarction, and 0.72 (0.49-1.06) for stroke. Heart failure causing admission to hospital or death occurred in 61 people in the rosiglitazone group and 29 in the active control group (HR 2.10, 1.35-3.27, risk difference per 1000 person-years 2.6, 1.1-4.1). Upper and distal lower limb fracture rates...... failure and of some fractures, mainly in women. Although the data are inconclusive about any possible effect on myocardial infarction, rosiglitazone does not increase the risk of overall cardiovascular morbidity or mortality compared with standard glucose-lowering drugs. FUNDING: GlaxoSmithKline plc, UK....

  15. 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

    Directory of Open Access Journals (Sweden)

    Jahan Ara Ainuddin

    2015-01-01

    Full Text Available 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 glycemic control. The patients were followed up till delivery. Maternal, and perinatal outcomes and pharmacotherapeutic characteristics were recorded on a proforma. Results. Maternal characteristics were comparable in metformin and insulin treated group. 84.9% patients in metformin group required add-on insulin therapy at mean gestational age of 26.58 ± 3.85 weeks. Less maternal weight gain (P24 hours in metformin group (P<0.01. Significant reduction in cost of treatment was found in metformin group. Conclusion. Metformin alone or with add-on insulin is an effective and cheap treatment option for patients with type 2 diabetes in pregnancy. This trial is registered with clinical trial registration number: Clinical trials.gov NCT01855763.

  16. Efeitos de 24 semanas de treinamento resistido sobre índices da aptidão aeróbia de mulheres idosas Effects of 24 weeks of resistance training on aerobic fitness indexes of older women

    Directory of Open Access Journals (Sweden)

    Marcelo Guido

    2010-08-01

    the main way to increase these indices. Conversely, resistance training (RT is not typically prescribed for this purpose. In elderly subjects, it has been suggested that RT may increase aerobic capacity; however, the literature is controversial. The purpose of the present study was to verify the effects of 24 weeks of RT on aerobic capacity indexes of elderly women. METHOD: Fifty elderly women voluntarily took part in this study and were divided into two possible groups: control group (CG - n=25; mean age of 68.00 ± 6.38 years and training group (TG - n=25; mean age of 68.04 ± 6.78 years. All volunteers underwent cardiopulmonary exercise test on treadmill until volitional exhaustion before and after the intervention period. A split plot ANOVA test was used to examine differences within and between groups. RESULTS: It was observed that the TG exhibited significant increase in the variables time of test and oxygen uptake for both AT and exhaustion moments. The CG did not show any significant alterations for any of the dependent variables. CONCLUSIONS: It can be concluded that 24 weeks of RT are capable of promoting improvement in performance during a cardiopulmonary exercise test in a sample of elderly women. Further studies are necessary to elucidate the mechanisms responsible for these adaptations.

  17. Open Label, Phase II Study to Evaluate Efficacy and Safety of Oral Nilotinib in Philadelphia Positive (Ph+) Chronic Myelogenous Leukemia (CML) Pediatric Patients.

    Science.gov (United States)

    2016-10-07

    Leukemia; Leukemia,Pediatric; Leukemia, Myleiod; Leukemia, Mylegenous, Chronic; Leukemia, Mylegenous, Accelerated; BCR-ABL Positive; Myeloproliferative Disorder; Bone Marrow Disease; Hematologic Diseases; Neoplastic Processes; Imatinib; Dasatinib; Enzyme Inhibitor; Protein Kinase Inhibitor

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

    OpenAIRE

    Domschke, Christoph

    2016-01-01

    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 fro...

  19. A 12 Week, Open Label, Phase I/IIa Study Using Apatone® for the Treatment of Prostate Cancer Patients Who Have Failed Standard Therapy

    Directory of Open Access Journals (Sweden)

    Basir Tareen, Jack L. Summers, James M. Jamison, Deborah R. Neal, Karen McGuire, Lowell Gerson, Ananias Diokno

    2008-01-01

    Full Text Available Purpose: To evaluate the safety and efficacy of oral Apatone® (Vitamin C and Vitamin K3 administration in the treatment of prostate cancer in patients who failed standard therapy. Materials and Methods: Seventeen patients with 2 successive rises in PSA after failure of standard local therapy were treated with (5,000 mg of VC and 50 mg of VK3 each day for a period of 12 weeks. Prostate Specific Antigen (PSA levels, PSA velocity (PSAV and PSA doubling times (PSADT were calculated before and during treatment at 6 week intervals. Following the initial 12 week trial, 15 of 17 patients opted to continue treatment for an additional period ranging from 6 to 24 months. PSA values were followed for these patients. Results: At the conclusion of the 12 week treatment period, PSAV decreased and PSADT increased in 13 of 17 patients (p ≤ 0.05. There were no dose-limiting adverse effects. Of the 15 patients who continued on Apatone after 12 weeks, only 1 death occurred after 14 months of treatment. Conclusion: Apatone showed promise in delaying biochemical progression in this group of end stage prostate cancer patients.

  20. Safety and Pharmacokinetics of Intravenous Zanamivir Treatment in Hospitalized Adults With Influenza: An Open-label, Multicenter, Single-Arm, Phase II Study

    Science.gov (United States)

    Marty, Francisco M.; Man, Choy Y.; van der Horst, Charles; Francois, Bruno; Garot, Denis; Máňez, Rafael; Thamlikitkul, Visanu; Lorente, José A.; Álvarez-Lerma, Francisco; Brealey, David; Zhao, Henry H.; Weller, Steve; Yates, Phillip J.; Peppercorn, Amanda F.

    2014-01-01

    Background. Intravenous zanamivir is a neuraminidase inhibitor suitable for treatment of hospitalized patients with severe influenza. Methods. Patients were treated with intravenous zanamivir 600 mg twice daily, adjusted for renal impairment, for up to 10 days. Primary outcomes included adverse events (AEs), and clinical/laboratory parameters. Pharmacokinetics, viral load, and disease course were also assessed. Results. One hundred thirty patients received intravenous zanamivir (median, 5 days; range, 1–11) a median of 4.5 days (range, 1–7) after onset of influenza; 83% required intensive care. The most common influenza type/subtype was A/H1N1pdm09 (71%). AEs and serious AEs were reported in 85% and 34% of patients, respectively; serious AEs included bacterial pulmonary infections (8%), respiratory failure (7%), sepsis or septic shock (5%), and cardiogenic shock (5%). No drug-related trends in safety parameters were identified. Protocol-defined liver events were observed in 13% of patients. The 14- and 28-day all-cause mortality rates were 13% and 17%. No fatalities were considered zanamivir related. Pharmacokinetic data showed dose adjustments for renal impairment yielded similar zanamivir exposures. Ninety-three patients, positive at baseline for influenza by quantitative polymerase chain reaction, showed a median decrease in viral load of 1.42 log10 copies/mL after 2 days of treatment. Conclusions. Safety, pharmacokinetic and clinical outcome data support further investigation of intravenous zanamivir. Clinical Trials Registration NCT01014988. PMID:23983212

  1. Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033-26033) : a randomised, open-label, phase 3 intergroup study

    NARCIS (Netherlands)

    Baumert, Brigitta G; Hegi, Monika E; van den Bent, Martin J; von Deimling, Andreas; Gorlia, Thierry; Hoang-Xuan, Khê; Brandes, Alba A; Kantor, Guy; Taphoorn, Martin J B; Hassel, Mohamed Ben; Hartmann, Christian; Ryan, Gail; Capper, David; Kros, Johan M; Kurscheid, Sebastian; Wick, Wolfgang; Enting, Roelien; Reni, Michele; Thiessen, Brian; Dhermain, Frederic; Bromberg, Jacoline E; Feuvret, Loic; Reijneveld, Jaap C; Chinot, Olivier; Gijtenbeek, Johanna M M; Rossiter, John P; Dif, Nicolas; Balana, Carmen; Bravo-Marques, Jose; Clement, Paul M; Marosi, Christine; Tzuk-Shina, Tzahala; Nordal, Robert A; Rees, Jeremy; Lacombe, Denis; Mason, Warren P; Stupp, Roger

    2016-01-01

    BACKGROUND: Outcome of low-grade glioma (WHO grade II) is highly variable, reflecting molecular heterogeneity of the disease. We compared two different, single-modality treatment strategies of standard radiotherapy versus primary temozolomide chemotherapy in patients with low-grade glioma, and asses

  2. A phase I, randomized, open-label, parallel-cohort, dose-finding study of elacridar (GF120918) and oral topotecan in cancer patients

    NARCIS (Netherlands)

    Kuppens, Isa E. L. M.; Witteveen, Els O.; Jewell, Roxanne C.; Radema, Sandra A.; Paul, Elaine M.; Mangum, Steve G.; Beijnen, Jos H.; Voest, Emile E.; Schellens, Jan H. M.

    2007-01-01

    Purpose: Breast cancer resistance protein (ABCG2) substantially limits the oral bioavailability of topotecan. Coadministration with elacridar, an inhibitor of breast cancer resistance protein mediated drug transport, increases the bioavailability of topotecan. The aim of this study was to establish

  3. An open-label, single-arm phase II clinical study of docetaxel plus lobaplatin for Chinese patients with pulmonary and hepatic metastasis of nasopharyngeal carcinoma.

    Science.gov (United States)

    Zhang, Shuai; Chen, Junni; Yang, Shiping; Lin, Shaomin

    2016-08-01

    To evaluate the efficacy and safety of the chemotherapy program of docetaxel combined with lobaplatin for Chinese patients with pulmonary and hepatic metastasis of nasopharyngeal carcinoma (NPC). This study included 37 NPC patients with pulmonary and hepatic metastasis. The chemotherapy program included docetaxel (75 mg/m, day 1) plus lobaplatin (30 mg/m, day 1). Cycle repetition was every 21 days. Patients were monitored for 7-41 months, with a median follow-up duration of 18 months. The total efficiency of this group was 67.6% and the disease control rate was 81.1%. The median progression-free survival was 9.4 months (95% confidence interval, 6.8-14.3 months), the median overall survival was 18.3 months (95% confidence interval, 13.7-22.8 months), and the 2-year survival rate was 37.8%. The main hematological toxicities were leukopenia (91.9%), anemia (81.1%), and thrombocytopenia (70.3%); other adverse reactions were mild. Changes in Epstein-Barr-DNA levels can basically reflect the dynamic changes in the efficacy of chemotherapy. Docetaxel combined with lobaplatin has a favorable outcome for the treatment of pulmonary and hepatic metastatic NPC. It has been a convenient regimen with tolerable toxicity. PMID:27088576

  4. An Open-label Phase 2 Study of UX007 (Triheptanoin) in Subjects With Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD)

    Science.gov (United States)

    2015-12-15

    Long-chain Fatty Acid Oxidation Disorders (LC-FAOD); Carnitine Palmitoyltransferase (CPT II) Deficiency; Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) Deficiency; Longchain 3-hydroxy-acyl-CoA Dehydrogenase (LCHAD) Deficiency; Trifunctional Protein (TFP) Deficiency

  5. Adjunctive Lisdexamfetamine Dimesylate Therapy in Adult Outpatients With Predominant Negative Symptoms of Schizophrenia: Open-Label and Randomized-Withdrawal Phases

    OpenAIRE

    Lasser, Robert A; Dirks, Bryan; Nasrallah, Henry; Kirsch, Courtney; Gao, Joseph; Pucci, Michael L.; Knesevich, Mary A; Lindenmayer, Jean-Pierre

    2013-01-01

    Negative symptoms of schizophrenia (NSS), related to hypodopaminergic activity in the mesocortical pathway and prefrontal cortex, are predictive of poor outcomes and have no effective treatment. Use of dopamine-enhancing drugs (eg, psychostimulants) has been limited by potential adverse effects. This multicenter study examined lisdexamfetamine dimesylate (LDX), a d-amphetamine prodrug, as adjunctive therapy to antipsychotics in adults with clinically stable schizophrenia and predominant NSS. ...

  6. Antiretroviral treatment is associated with iron deficiency in HIV-infected Malawian women that is mitigated with supplementation, but is not associated with infant iron deficiency during 24 weeks of exclusive breastfeeding

    Science.gov (United States)

    Widen, Elizabeth M; Bentley, Margaret E; Chasela, Charles S; Kayira, Dumbani; Flax, Valerie L; Kourtis, Athena P; Ellington, Sascha R; Kacheche, Zebrone; Tegha, Gerald; Jamieson, Denise J; van der Horst, Charles M; Allen, Lindsay H; Shahab-Ferdows, Setareh; Adair, Linda S

    2015-01-01

    Objective In resource-limited settings without safe alternatives to breastfeeding, the WHO recommends exclusive breastfeeding and antiretroviral (ARV) prophylaxis. Given the high prevalence of anemia among HIV-infected women, mothers and their infants (via fetal iron accretion) may be at risk of iron deficiency. We assessed the effects of maternal micronutrient-fortified lipid-based nutrient supplements (LNS) and maternal ARV treatment or infant ARV prophylaxis on maternal and infant iron status during exclusive breastfeeding from birth to 24 weeks. Methods The Breastfeeding, Antiretrovirals, and Nutrition Study was a randomized controlled trial conducted in Lilongwe, Malawi from 2004-2010. HIV-infected mothers (CD4>200 cells/ul) and their infants were randomly assigned to 28-week interventions: maternal-LNS/maternal-ARV (n=424), maternal-LNS/infant-ARV (n=426), maternal-LNS (n=334), maternal-ARV (n=425), infant-ARV (n=426), or control (n=334). Longitudinal models tested intervention effects on hemoglobin (Hb). In a subsample (n=537) with multiple iron indicators, intervention effects on Hb, transferrin receptors (TfR) and ferritin were tested with linear and Poisson regression. Results In longitudinal models, LNS effects on maternal and infant Hb were minimal. In subsample mothers, maternal ARVs were associated with tissue iron depletion (TfR>8.3 mg/L) (Risk ratio (RR): 3.1, p0.1). In subsample infants, interventions were not associated with impaired iron status (all p-values>0.1). Conclusions Maternal ARV treatment with protease inhibitors is associated with maternal tissue iron depletion; but LNS mitigates adverse effects. ARVs do not appear to influence infant iron status; however, extended use needs to be evaluated. PMID:25723140

  7. Fluticasone/formoterol combination therapy is as effective as fluticasone/salmeterol in the treatment of asthma, but has a more rapid onset of action: an open-label, randomized study

    Directory of Open Access Journals (Sweden)

    McAulay Kirsten

    2011-05-01

    Full Text Available Abstract Background The inhaled corticosteroid (ICS fluticasone propionate (fluticasone and the long-acting β2-agonist (LABA formoterol fumarate (formoterol are being made available as a combination product (fluticasone/formoterol, flutiform® in a single aerosol inhaler. This 12-week, open-label, randomized, active-controlled, parallel-group, multicentre, phase 3 study compared the efficacy and safety of fluticasone/formoterol with the commercially available combination product fluticasone/salmeterol. Methods Patients aged ≥ 18 years (N = 202 with mild-to-moderate–severe, persistent asthma for ≥ 6 months prior to screening were included in the study. After a screening phase (4–10 days, eligible patients were randomized 1:1 to receive fluticasone/formoterol or fluticasone/salmeterol during the 12-week treatment period. The primary objective was to demonstrate non-inferiority of fluticasone/formoterol versus fluticasone/salmeterol, measured by pre-dose forced expiratory volume in the first second (FEV1, at week 12. Results Fluticasone/formoterol was comparable to fluticasone/salmeterol for the primary efficacy endpoint, mean pre-dose FEV1 at week 12. The new combination was also comparable to fluticasone/salmeterol for change from baseline to week 12 in pre-dose FEV1, change from pre-dose FEV1 at baseline to 2-hour post-dose FEV1 at week 12 and discontinuations due to lack of efficacy. Importantly, fluticasone/formoterol was superior to fluticasone/salmeterol in time to onset of action throughout the duration of the study. The two treatments demonstrated similar results for various other secondary efficacy parameters, including other lung function tests, patient-reported outcomes, rescue medication use, asthma exacerbations and Asthma Quality of Life Questionnaire scores. Fluticasone/formoterol was well tolerated and had a good safety profile that was similar to fluticasone/salmeterol. Conclusions The results of this study indicate that

  8. Open-label observational study to assess the efficacy and safety of aprepitant for chemotherapy-induced nausea and vomiting prophylaxis in Indian patients receiving chemotherapy with highly emetogenic chemotherapy/moderately emetogenic chemotherapy regimens

    OpenAIRE

    Hingmire Sachin; Raut Nirmal

    2015-01-01

    Context: Currently, there is limited data on the prevention of chemotherapy-induced nausea and vomiting (CINV) in Indian population with aprepitant containing regimens. Aims: The aim was to assess the Efficacy and Safety of Aprepitant for the prevention of nausea and vomiting associated with highly emetogenic chemotherapy/moderately emetogenic chemotherapy (HEC/MEC) regimens. Settings and Design: Investigator initiated, multicentric, open-label, prospective, noncomparative, observational tria...

  9. Long-term efficacy and safety of incobotulinumtoxinA and conventional treatment of poststroke arm spasticity: a prospective, non-interventional, open-label, parallel-group study

    OpenAIRE

    Dressler, Dirk; Rychlik, Reinhard; Kreimendahl, Fabian; Schnur, Nicole; Lambert-Baumann, Judith

    2015-01-01

    Objective To compare the efficacy and safety of incobotulinumtoxinA with conventional antispastic therapy for poststroke arm spasticity in routine clinical practice over a 1-year period. Design Prospective, non-interventional, open-label, parallel-group study. Setting 47 centres in Germany. Participants Patients with poststroke arm spasticity; 108 receiving incobotulinumtoxinA, 110 conventional therapy. Intervention Conventional antispastic treatment including oral antispastic medications, ph...

  10. An open-label randomized clinical trial of prophylactic paracetamol coadministered with 7-valent pneumococcal conjugate vaccine and hexavalent diphtheria toxoid, tetanus toxoid, 3-component acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b vaccine

    OpenAIRE

    Rose, Markus A.; Jürgens, Christine; Schmoele-Thoma, Beate; Gruber, William C.; Baker, Sherryl; Zielen, Stefan

    2013-01-01

    BACKGROUND: In two clinical trials, low-grade fever was observed more frequently after coadministration than after separate administration of two recommended routine pediatric vaccines. Since fever is an important issue with vaccine tolerability, we performed this open-label study on the efficacy and safety of prophylactic use of paracetamol (acetaminophen, Benuron(R)) in children administered routine 7-valent pneumococcal conjugate vaccine (PCV-7) coadministered with hexavalent vaccine (diph...

  11. The safety and effectiveness of open-label extended-release carbamazepine in the treatment of children and adolescents with bipolar I disorder suffering from a manic or mixed episode

    OpenAIRE

    Findling RL; Ginsberg LD

    2014-01-01

    Robert L Findling,1,2 Lawrence D Ginsberg31Division of Child and Adolescent Psychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, 2Kennedy Krieger Institute, Baltimore, MD, USA; 3Red Oak Psychiatry Associates, PA, Houston, TX, USAObjective: To assess the safety and effectiveness of open-label treatment with extended-release carbamazepine (ERC) in pediatric subjects suffering from bipolar I disorder.Method: Medically healthy youths aged 10–17&nbs...

  12. Efficacy, safety and tolerability of ongoing statin plus ezetimibe versus doubling the ongoing statin dose in hypercholesterolemic Taiwanese patients: an open-label, randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Yu Chih-Chieh

    2012-05-01

    Full Text Available Abstract Background Reducing low-density lipoprotein cholesterol (LDL-C is associated with reduced risk for major coronary events. Despite statin efficacy, a considerable proportion of statin-treated hypercholesterolemic patients fail to reach therapeutic LDL-C targets as defined by guidelines. This study compared the efficacy of ezetimibe added to ongoing statins with doubling the dose of ongoing statin in a population of Taiwanese patients with hypercholesterolemia. Methods This was a randomized, open-label, parallel-group comparison study of ezetimibe 10 mg added to ongoing statin compared with doubling the dose of ongoing statin. Adult Taiwanese hypercholesterolemic patients not at optimal LDL-C levels with previous statin treatment were randomized (N = 83 to ongoing statin + ezetimibe (simvastatin, atorvastatin or pravastatin + ezetimibe at doses of 20/10, 10/10 or 20/10 mg or doubling the dose of ongoing statin (simvastatin 40 mg, atorvastatin 20 mg or pravastatin 40 mg for 8 weeks. Percent change in total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C and triglycerides, and specified safety parameters were assessed at 4 and 8 weeks. Results At 8 weeks, patients treated with statin + ezetimibe experienced significantly greater reductions compared with doubling the statin dose in LDL-C (26.2% vs 17.9%, p = 0.0026 and total cholesterol (20.8% vs 12.2%, p = 0.0003. Percentage of patients achieving treatment goal was greater for statin + ezetimibe (58.6% vs doubling statin (41.2%, but the difference was not statistically significant (p = 0.1675. The safety and tolerability profiles were similar between treatments. Conclusion Ezetimibe added to ongoing statin therapy resulted in significantly greater lipid-lowering compared with doubling the dose of statin in Taiwanese patients with hypercholesterolemia. Studies to assess clinical outcome benefit are ongoing. Trial registration Registered at ClinicalTrials.gov: NCT00652327

  13. Improvement of executive functions in boys with attention deficit hyperactivity disorder: an open-label follow-up study with once-daily atomoxetine.

    Science.gov (United States)

    Gau, Susan Shur-Fen; Shang, Chi-Yung

    2010-03-01

    Atomoxetine is efficacious in reducing symptoms of attention deficit hyperactivity disorder (ADHD) but its effect on executive functions needs more investigation. We examined the effect of atomoxetine on a wide range of non-verbal executive functions among 30 drug-naive male patients with DSM-IV ADHD, aged 8-16 yr, in an open-label 12-wk atomoxetine treatment trial. Before administration of atomoxetine, the participants were assessed by psychiatric interviews, the WISC-III, and the tasks involving executive functions of the Cambridge Neuropsychological Test Automated Battery (CANTAB): Intra-dimensional/Extra-dimensional Shifts (IED), Rapid Visual Information Processing (RVIP), Spatial Span (SSP), Spatial Working Memory (SWM), and Stockings of Cambridge (SOC); and reassessed at weeks 4 and 12. All the raw scores of the CANTAB were transformed to z scores based on a normative sample of 180 children aged 8-16 yr. Results showed significant improvement in executive functions after treatment with atomoxetine for 4 wk or 12 wk including improved shifting and flexibility of attention in the IED; improved spatial short-term memory in the SSP; improved sustained attention and increased response inhibition in the RVIP; improved spatial working memory in the SWM; and improved spatial planning and problem solving in the SOC. Our findings suggested that atomoxetine was associated with significant improvement in various non-verbal executive functions among boys with ADHD, in addition to its well-known efficacy in ADHD-related symptom reductions. However, owing to lack of a placebo-controlled trial design, the findings should be interpreted with caution that changes in performance may be due to practice effects.

  14. An Open Label Clinical Trial of a Multi-Ingredient Anti-Aging Moisturizer Designed to Improve the Appearance of Facial Skin.

    Science.gov (United States)

    Herndon, James H; Jiang, Lily; Kononov, Tatiana; Fox, Theresa

    2015-07-01

    An open label clinical trial was conducted to determine the effectiveness of a multi-ingredient anti-aging moisturizer designed to improve the appearance of facial skin. Parameters studied included fine lines and wrinkles, clarity/brightness, visual roughness, tactile roughness, evenness of skin tone (redness), evenness of skin tone (hyperpigmentation) and overall appearance. Thirty-seven female subjects, ages 35-60 years completed the study. Effective ingredients incorporated into the facial anti-aging moisturizer include: Astragalus membranaceus root extract, a peptide blend including palmitoyl tripeptide-38, standardized rosemary leaf extract (ursolic acid), tetrahexyldecyl ascorbate (THD ascorbate) and ubiquinone (coenzyme Q10). Subjects were instructed to apply the moisturizer twice daily, once in the morning and once in the evening. Subjects were evaluated at baseline and after 4, 8, and 12 weeks of product usage. Clinical evaluations were conducted at each visit. A self-assessment questionnaire was conducted at week 4, week 8, and week 12. The self-assessment questionnaire included product efficacy inquiries and product aesthetic inquiries. Digital photography was conducted at baseline, week 8, and week 12. After 8 weeks of twice daily use, clinical evaluation results show that the multi-ingredient anti-aging moisturizer produced a statistically significant improvement in the scores of all clinical grading parameters assessed compared to baseline. A greater statistically significant improvement was seen at 12 weeks. At week 12, there was a statistically significant percentage of favorable results versus unfavorable results in all product efficacy and product aesthetic self-assessment questionnaire results. Digital photography supported the clinical grading and self-assessment questionnaire results. Additionally, the multi-ingredient anti-aging moisturizer is judged to be mild and well tolerated. Several tolerability parameters were assessed at all time

  15. Comparative randomized open-label trial on efficacy and safety of Persen® and Persen® Night herbal extracts in patients with short-term insomnia

    Directory of Open Access Journals (Sweden)

    A. P. Rachin

    2016-01-01

    Full Text Available Herbal sedatives serve an alternative to antipsychotics and hypnotics aimed to alleviate symptoms of anxious disorders and insomnia. Valeriana officinalis L., Mentha piperita L. and Melissa officinalis are most widely used in neurology as sedatives of herbal origin. We present the results of a randomized open-label trial on efficiency and safety of Persen® and Persen® Night containing extracts of the above mentioned plants in patients with short-term insomnia. The study consisted of 60 subjects of 18–65 y.o. (mean 42.4 ± 6.9 y.o. with short-term insomnia due to adjustment disorder or mixed anxiety-depressive disorders: 30 of them got Persen® 2 tablets a day and 30 – Persen® Night, 1 capsule 30–60 min before sleep during 4 weeks. The majority (76.5 % of patients referred the onset of insomnia with psychosocial traumatic stressor. Persen® Night’s main action was found on superficial sleep, number of night awakenings, sleep onset rate. At the end of the therapy with this substance 39.7 % of patients fell asleep in 10–15 min, and 92.2 % – in 30 min, accordingly, while for Persen® at 17.4 and 80.3 % accordingly (р < 0.05. In the meantime Persen® decreased the bad sleep perception at awakening and day somnolence, mostly attributed to the mood improvement and decrease of anxiety. Levels of efficacy and safety for both substances were significant, allowing to regard them as potential phytotherapeutic agent in the treatment of insomnia and mixed anxiety-depressive disorders.

  16. WIN OVER study: Efficacy and safety of olmesartan in Indian hypertensive patients: Results of an open label, non-comparative, multi-centric, post marketing observational study

    Science.gov (United States)

    Kumbla, D.K.; Kumar, S.; Reddy, Y.V.; Trailokya, A.; Naik, M.

    2014-01-01

    Background Hypertension is a global health problem. Multiple classes of drugs including angiotensin receptor blockers (ARBs) are available for the treatment of hypertension. Olmesartan is a relatively newer ARB used in hypertension management. Objective To assess the efficacy and safety of WIN-BP (Olmesartan 20 mg/40 mg) tablet in Indian patients with hypertension. Material and methods An open label, non-comparative, multi-centric, real world post marketing observational study included Indian adult hypertensive patients who were treated with olmesartan 20 mg/40 mg tablet once daily for six months. The primary outcome was reduction of systolic blood pressure (SBP) to <140 mmHg and diastolic BP (DBP) to <90 mmHg at 3 and 6 months after initiation of treatment with olmesartan. All reported adverse events were recorded. Results A total of 8940 patients were enrolled in this study. Baseline SBP of 164 mmHg was reduced to 153, 145, 134 and 130 mmHg at the end of 15 days, 1, 3 and 6 months respectively. Similarly, baseline DBP of 100 mmHg was reduced to 93, 89, 84 and 82 mmHg at the end of 15 days, 1, 3 and 6 months respectively. The reduction in both systolic and diastolic blood pressure from day 15 to month 6 was statistically significant (p < 0.0001) with olmesartan treatment. The percentage of responders for both systolic and diastolic blood pressure increased consistently from day 15 to month 6. Only 0.08% patients reported the adverse events. No serious adverse event was reported in the study. Conclusion Olmesartan 20 mg/40 mg is effective and well tolerated without any serious adverse events in patients with hypertension. PMID:24973841

  17. Open label smoking cessation with varenicline is associated with decreased glutamate levels and functional changes in anterior cingulate cortex: preliminary findings

    Directory of Open Access Journals (Sweden)

    Muriah Dawn Wheelock

    2014-07-01

    Full Text Available Rationale: Varenicline, the most effective single agent for smoking cessation, is a partial agonist at α4β2 nicotinic acetylcholine receptors. Increasing evidence implicates glutamate in the pathophysiology of addiction and one of the benefits of treatment for smoking cessation is the ability to regain cognitive control. Objective: To evaluate the effects of 12 week varenicline administration on glutamate levels in the dorsal anterior cingulate cortex (dACC and functional changes within the cognitive control network.Methods: We used single-voxel proton magnetic resonance spectroscopy (1H-MRS in the dACC and functional MRI (fMRI during performance of a Stroop color-naming task before and after smoking cessation with varenicline in 11 healthy smokers (open label design. Using the dACC as a seed region, we evaluated functional connectivity changes using a psychophysiological interaction (PPI analysis. Results: We observed a significant decrease in dACC glutamate + glutamine (Glx/Cr levels as well as significant blood oxygen level-dependent signal (BOLD decreases in the rostral ACC/medial orbitofrontal cortex and precuneus/posterior cingulate cortex. These BOLD changes are suggestive of alterations in default mode network (DMN function and are further supported by the results of the PPI analysis that revealed changes in connectivity between the dACC and regions of the DMN. Baseline measures of nicotine dependence and craving positively correlated with baseline Glx/Cr levels.Conclusions: These results suggest possible mechanisms of action for varenicline such as reduction in Glx levels in dACC and shifts in BOLD activities between large scale brain networks. They also suggest a role for ACC Glx in the modulation of behavior. Due to the preliminary nature of this study (lack of control group and small sample size, future studies are needed to replicate these findings.

  18. A Preliminary, Open Label, Single-arm Study of Calcipotriene/Betamethasone Topical Suspension as a Supplement to Non-biologic Systemic Therapy for Psoriasis

    Science.gov (United States)

    Kupetsky, Erine; Houston, Neil A.M.

    2016-01-01

    Background: Calcipotriene/betamethasone topical suspension is a topical therapy that is often used as monotherapy as a first-line treatment for plaque psoriasis. The objective of this preliminary, open label, single arm study was to determine the efficacy of adding a topical suspension to a traditional systemic therapy for psoriasis, either methotrexate or acitretin. Methods: In this exploratory study, eight patients with chronic plaque psoriasis who were on stable methotrexate or acitretin treatment without clearance were treated with once-daily calcipotriene/betamethasone topical suspension. Subjects completed five study visits over 12 weeks. Primary outcome measure was improvement of two or more points in Investigator Global Assessment. Secondary endpoints included change in Body Surface Area, Dermatology Life Quality Index, and Patient’s Global Assessment from baseline to Week 12. Results: Overall, the median decrease in Investigator Global Assessment over 12 weeks was 1.5 points, with 50 percent of subjects experiencing a drop of two or more points in Investigator Global Assessment. All eight subjects had a reduction in Body Surface Area and Patient’s Global Assessment. There was a mean decrease in Dermatology Life Quality Index score of 78.9 percent, showing improved patient quality of life. In addition, all patients tolerated the treatment well and 6 of 8 patients had improved satisfaction level with their treatment by the end of the study. Conclusion: The topical suspension was effective and well-tolerated in conjunction with stable methotrexate or acitretin treatment in all eight patients in this study. These results support the feasibility of a larger scale study to further investigate the efficacy of these treatment combinations. The trial is registered at ClinicalTrials.gov, number NCT01761019. PMID:27462386

  19. Efficacy of two versus three-day regimens of dihydroartemisinin-piperaquine for uncomplicated malaria in military personnel in northern Cambodia: an open-label randomized trial.

    Directory of Open Access Journals (Sweden)

    Chanthap Lon

    Full Text Available Emerging antimalarial drug resistance in mobile populations remains a significant public health concern. We compared two regimens of dihydroartemisinin-piperaquine in military and civilians on the Thai-Cambodian border to evaluate national treatment policy.Efficacy and safety of two and three-day regimens of dihydroartemisinin-piperaquine were compared as a nested open-label evaluation within a malaria cohort study in 222 otherwise healthy volunteers (18% malaria-infected at baseline. The first 80 volunteers with slide-confirmed Plasmodium falciparum or vivax malaria were randomized 1:1 to receive either regimen (total dose 360 mg dihydroartemisinin and 2880 mg piperaquine and followed weekly for up to 6 months. The primary endpoint was malaria recurrence by day 42. Volunteers with vivax infection received primaquine at study discharge with six months follow-up.Eighty patients (60 vivax, 15 falciparum, and 5 mixed were randomized to dihydroartemisinin-piperaquine. Intention-to-treat all-species efficacy at Day 42 was 85% for the two-day regimen (95% CI 69-94 and 90% for the three-day regimen (95% CI 75-97. PCR-adjusted falciparum efficacy was 75% in both groups with nearly half (45% still parasitemic at Day 3. Plasma piperaquine levels were comparable to prior published reports, but on the day of recrudescence were below measurable in vitro piperaquine IC50 levels in all falciparum treatment failures.In the brief period since introduction of dihydroartemisinin-piperaquine, there is early evidence suggesting declining efficacy relative to previous reports. Parasite IC50 levels in excess of plasma piperaquine levels seen only in treatment failures raises concern for clinically significant piperaquine resistance in Cambodia. These findings warrant improved monitoring of clinical outcomes and follow-up, given few available alternative drugs.ClinicalTrials.gov NCT01280162.

  20. Tetrabenazine as anti-chorea therapy in Huntington Disease: an open-label continuation study. Huntington Study Group/TETRA-HD Investigators

    Directory of Open Access Journals (Sweden)

    Frank Samuel

    2009-12-01

    Full Text Available Abstract Background Tetrabenazine (TBZ selectively depletes central monoamines by reversibly binding to the type-2 vesicular monoamine transporter. A previous double blind study in Huntington disease (HD demonstrated that TBZ effectively suppressed chorea, with a favorable short-term safety profile (Neurology 2006;66:366-372. The objective of this study was to assess the long-term safety and effectiveness of TBZ for chorea in HD. Methods Subjects who completed the 13-week, double blind protocol were invited to participate in this open label extension study for up to 80 weeks. Subjects were titrated to the best individual dose or a maximum of 200 mg/day. Chorea was assessed using the Total Maximal Chorea (TMC score from the Unified Huntington Disease Rating Scale. Results Of the 75 participants, 45 subjects completed 80 weeks. Three participants terminated due to adverse events (AEs including depression, delusions with associated previous suicidal behavior, and vocal tics. One subject died due to breast cancer. The other 26 subjects chose not to continue on with each ensuing extension for various reasons. When mild and unrelated AEs were excluded, the most commonly reported AEs (number of subjects were sedation/somnolence (18, depressed mood (17, anxiety (13, insomnia (10, and akathisia (9. Parkinsonism and dysphagia scores were significantly increased at week 80 compared to baseline. At week 80, chorea had significantly improved from baseline with a mean reduction in the TMC score of 4.6 (SD 5.5 units. The mean dosage at week 80 was 63.4 mg (range 12.5-175 mg. Conclusions TBZ effectively suppresses HD-related chorea for up to 80 weeks. Patients treated chronically with TBZ should be monitored for parkinsonism, dysphagia and other side effects including sleep disturbance, depression, anxiety, and akathisia. Trial Registration Clinicaltrials.gov registration number (initial study: NCT00219804

  1. Psychosocial outcomes after initial treatment of erectile dysfunction with tadalafil once daily, tadalafil on demand or sildenafil citrate on demand: results from a randomized, open-label study.

    Science.gov (United States)

    Hatzimouratidis, K; Buvat, J; Büttner, H; Vendeira, P A S; Moncada, I; Boehmer, M; Henneges, C; Boess, F G

    2014-01-01

    Initiation of ED treatment with a particular PDE5I may influence treatment-adherence and other outcomes. In this multicenter, open-label study, men with ED, naïve to PDE5I, were randomized to tadalafil 5 mg once-a-day (OaD; N=257), 10 mg on demand (PRN; N = 252) or sildenafil-citrate (sildenafil) 50 mg PRN (N = 261) for 8 weeks (dose adjustments allowed), followed by 16 weeks of pragmatic treatment (switching between PDE5I allowed). Primary outcomes (treatment-adherence) were reported previously. Here, we report effects on: Psychological and Interpersonal Relationship Scales, Self-Esteem and Relationship (SEAR) questionnaire, ED Inventory of Treatment Satisfaction (EDITS), International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP) and Global Assessment Questions (GAQ). Mixed-model for repeated measures and analysis of covariance were used to analyze changes from baseline; GAQ-responses were evaluated by logistic regression. Analyses were adjusted for treatment, country, ED-severity, baseline and baseline-by-treatment interaction. Patients randomized to tadalafil OaD or PRN reported greater improvement (least-square mean (s.e.) change) in Sexual Self-Confidence (OaD +0.90 (0.048), PRN +0.93 (0.050), vs +0.73 (0.049); P=0.006 and P=0.001) and Spontaneity (OaD +0.11 (0.035), PRN +0.13 (0.035), vs +0.02 (0.035); P = 0.044 and P = 0.010) compared with sildenafil. Improvements in GAQ and SEP responses, IIEF-EF, orgasmic function, sexual desire, overall satisfaction domains, SEAR and EDITS scores did not differ significantly between treatment groups. PMID:24784894

  2. Study protocol for a randomized controlled trial to assess the feasibility of an open label intervention to improve hydroxyurea adherence in youth with sickle cell disease

    Science.gov (United States)

    Smaldone, Arlene; Findley, Sally; Bakken, Suzanne; Matiz, L. Adriana; Rosenthal, Susan L.; Jia, Haomiao; Matos, Sergio; Manwani, Deepa; Green, Nancy S.

    2016-01-01

    Background Community health workers (CHW) are increasingly recognized as a strategy to improve health outcomes for the underserved with chronic diseases but has not been formally explored in adolescents with sickle cell disease (SCD). SCD primarily affects African American, Hispanic and other traditionally underserved populations. Hydroxyurea (HU), an oral, once-daily medication, is the only approved therapeutic drug for sickle cell disease and markedly reduces symptoms, morbidity and mortality and improves quality of life largely by increasing hemoglobin F blood levels. This paper presents the rationale, study design and protocol for an open label randomized controlled trial to improve parent-youth partnerships in self-management and medication adherence to HU in adolescents with SCD. Methods/Design A CHW intervention augmented by text messaging was designed for adolescents with SCD ages 10–18 years and their parents to improve daily HU adherence. Thirty adolescent parent dyads will be randomized with 2:1 intervention group allocation. Intervention dyads will establish a relationship with a culturally aligned CHW to identify barriers to HU use, identify cues to build a habit, and develop a dyad partnership to improve daily HU adherence and achieve their individualized “personal best” hemoglobin F target. Intervention feasibility, acceptability and efficacy will be assessed via a 2-site trial. Outcomes of interest are HU adherence, dyad self-management communication, quality of life, and resource use. Discussion Despite known benefits, poor HU adherence is common. If feasible and acceptable, the proposed intervention may improve health of underserved adolescents with SCD by enhancing long-term HU adherence. PMID:27327779

  3. Comparative efficacy trial of cupping and serkangabin versus conventional therapy of migraine headaches: A randomized, open-label, comparative efficacy trial

    Directory of Open Access Journals (Sweden)

    Mohammad Dehghani Firoozabadi

    2014-01-01

    Full Text Available Background: Migraine headaches are the most common acute and recurrent headaches. Current treatment of a migraine headache consists of multiple medications for control and prevention of recurrent attacks. Global emergence of alternative medicine led us to examine the efficacy of cupping therapy plus serkangabin syrup in the treatment of migraine headaches. Materials and Methods: This study was a randomized, controlled, open-label, comparative efficacy trial. We randomly assigned patients with migraine into cupping therapy plus serkangabin group (30 patients and conventional treatment group (30 patients. An investigator assessed the severity of headache, frequency of attacks in a week and duration of attacks per hour in 5 visits (at the end of 2 weeks, 1, 3 and 6 months. Generalized estimating equations approach was used to analyze repeated measures data to compare outcomes in both groups. Results: Average age for cupping therapy group and conventional treatment group were 31.7 (±7.6 and 32.6 (±12.7 years, respectively (P = 0.45. After treatment for 2 weeks; and 1, 3 and 6 months, severity of headache (P = 0.80, frequency of migraine attacks (P = 0.63 and duration of attacks per hours (P = 0.48 were similar in conventional and cupping groups but these symptoms were decreased in each group during the study (P < 0.001. Conclusion: There was no significant difference between cupping plus serkangabin therapy and conventional treatment in the treatment and prophylaxis of migraine. The alternative therapy may be used in cases of drug intolerance, no medication response, and in primary care.

  4. Effect of Vitamin D supplementation on glycemic parameters and progression of prediabetes to diabetes: A 1-year, open-label randomized study

    Directory of Open Access Journals (Sweden)

    Mohammad Shafi Kuchay

    2015-01-01

    Full Text Available Background: Whether Vitamin D supplementation in prediabetes subjects prevents the development of diabetes is a matter of debate, and the results are inconsistent. This open-label, randomized study in subjects with prediabetes evaluated the effect of 12 months of Vitamin D supplementation on glycemic parameters and progression of prediabetes to diabetes in an ethnically homogeneous Kashmiri population. Materials and Methods: A total of 147 subjects were diagnosed as prediabetes out of which 137 subjects were randomized to receive in addition to standard lifestyle measures, either Vitamin D 60,000 IU weekly for 4 weeks and then 60,000 IU monthly (n = 69 or no Vitamin D (n = 68. Fasting plasma glucose (FPG, 2-h plasma glucose and A1C levels were estimated at 0, 6 and 12 months. Changes in FPG, 2-h plasma glucose, A1C level and the proportion of subjects developing diabetes were assessed among 129 subjects. Results: At 12 months, A1C levels were significantly lesser (5.7% ± 0.4% in the Vitamin D supplemented group when compared with non-Vitamin D supplemented (6.0% ± 0.3%. Similarly, FPG (97 ± 7 and 2-h plasma glucose (132 ± 16 were significantly less in Vitamin D supplemented group as compared with non-Vitamin D supplemented group (FPG = 116 ± 6 and 2-h plasma glucose = 157 ± 25 at 12 months. Nine out of 65 in non-Vitamin D supplemented and seven out of 64 in the Vitamin D supplemented group developed diabetes. Conclusions: Vitamin D supplementation in prediabetes subjects significantly lowered FPG, 2-h plasma glucose and A1C levels.

  5. Efficacy and safety of open-label etanercept on extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis and psoriatic arthritis: part 1 (week 12) of the CLIPPER study

    Science.gov (United States)

    Horneff, Gerd; Burgos-Vargas, Ruben; Constantin, Tamas; Foeldvari, Ivan; Vojinovic, Jelena; Chasnyk, Vyacheslav G; Dehoorne, Joke; Panaviene, Violeta; Susic, Gordana; Stanevica, Valda; Kobusinska, Katarzyna; Zuber, Zbigniew; Mouy, Richard; Rumba-Rozenfelde, Ingrida; Breda, Luciana; Dolezalova, Pavla; Job-Deslandre, Chantal; Wulffraat, Nico; Alvarez, Daniel; Zang, Chuanbo; Wajdula, Joseph; Woodworth, Deborah; Vlahos, Bonnie; Martini, Alberto; Ruperto, Nicolino

    2014-01-01

    Objective To investigate the efficacy and safety of etanercept (ETN) in paediatric subjects with extended oligoarticular juvenile idiopathic arthritis (eoJIA), enthesitis-related arthritis (ERA), or psoriatic arthritis (PsA). Methods CLIPPER is an ongoing, Phase 3b, open-label, multicentre study; the 12-week (Part 1) data are reported here. Subjects with eoJIA (2–17 years), ERA (12–17 years), or PsA (12–17 years) received ETN 0.8 mg/kg once weekly (maximum 50 mg). Primary endpoint was the percentage of subjects achieving JIA American College of Rheumatology (ACR) 30 criteria at week 12; secondary outcomes included JIA ACR 50/70/90 and inactive disease. Results 122/127 (96.1%) subjects completed the study (mean age 11.7 years). JIA ACR 30 (95% CI) was achieved by 88.6% (81.6% to 93.6%) of subjects overall; 89.7% (78.8% to 96.1%) with eoJIA, 83.3% (67.2% to 93.6%) with ERA and 93.1% (77.2% to 99.2%) with PsA. For eoJIA, ERA, or PsA categories, the ORs of ETN vs the historical placebo data were 26.2, 15.1 and 40.7, respectively. Overall JIA ACR 50, 70, 90 and inactive disease were achieved by 81.1, 61.5, 29.8 and 12.1%, respectively. Treatment-emergent adverse events (AEs), infections, and serious AEs, were reported in 45 (35.4%), 58 (45.7%), and 4 (3.1%), subjects, respectively. Serious AEs were one case each of abdominal pain, bronchopneumonia, gastroenteritis and pyelocystitis. One subject reported herpes zoster and another varicella. No differences in safety were observed across the JIA categories. Conclusions ETN treatment for 12 weeks was effective and well tolerated in paediatric subjects with eoJIA, ERA and PsA, with no unexpected safety findings. PMID:23696632

  6. Milnacipran and venlafaxine at flexible doses (up to 200 mg/day in the outpatient treatment of adults with moderate-to-severe major depressive disorder: a 24-week randomized, double-blind exploratory study

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Olié

    2010-03-01

    Full Text Available Jean-Pierre Olié1, David Gourion2, Agnès Montagne3, Michel Rostin4, Marie-France Poirier11Service de Santé Mentale et Thérapeutique, Centre Hospitalier Sainte-Anne, Paris, France; 217 rue des Marronniers, 75016 Paris, France; 3Pierre Fabre Médicament, Labège, France; 4Pierre Fabre Médicament, Castres, FranceAbstract: The objective of this exploratory, multicenter, randomized, double-blind study, was to evaluate the efficacy and safety/tolerability of milnacipran and venlafaxine administered at flexible doses (100, 150 or 200 mg/day, bid administration for 24 weeks (including 4 weeks up titration period in the outpatient treatment of adults presenting with a moderate or severe episode of major depressive disorder (MDD without high suicidal risk (MINI-DSM IV-TR. Of the 195 patients included, 134 (68.7% completed the study. At baseline the two groups were similar, except there was a higher proportion of patients whose episode was severe-DSM IV in the milnacipran group (63.3% versus 54.0% in the venlafaxine group. The initial MADRS score (mean 31.0 decreased progressively during the study, and this decrease was in the two treatment groups (n = 177: 90 milnacipran; 87 venlafaxine at week 24 (observed case/OC, mean change –23.1 milnacipran; –22.4 venlafaxine. The rate of MADRS response (reduction ≥ 50% at week 8 and week 24-last observation carried forward/LOCF was similar in the two groups (week 8: 64.4% milnacipran; 65.5% venlafaxine; week 24: 70% milnacipran; 77% venlafaxine, as was the rate of MADRS remission (score ≤ 10 (week 8: 42.2% milnacipran; 42.5% venlafaxine; week 24: 52.2% milnacipran; 62.1% venlafaxine. In both groups, the most common adverse events were: nausea, dizziness, headache, hyperhidrosis and, in males, genito-urinary problems. The overall safety/tolerability and efficacy profiles of milnacipran and venlafaxine administered at flexible dosages (up to 200 mg/day were similar in the long term treatment of adults

  7. Effect of Oral Beta-Hydroxy-Beta-Methylbutyrate (HMB Supplementation on Physical Performance in Healthy Old Women Over 65 Years: An Open Label Randomized Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Linda Berton

    Full Text Available Although older people are particularly liable to sarcopenia, limited research is available on beta-hydroxy-beta-methylbutyrate (HMB supplementation in this population, particularly in healthy subjects. In this parallel-group, randomized, controlled, open-label trial, we aimed to evaluate whether an oral supplement containing 1.5 g of calcium HMB for 8 weeks could improve physical performance and muscle strength parameters in a group of community-dwelling healthy older women. Eighty healthy women attending a twice-weekly mild fitness program were divided into two equal groups of 40, and 32 of the treated women and 33 control completed the study. We considered a change in the Short Physical Performance Battery (SPPB score as the primary outcome and changes in the peak torque (PT isometric and isokinetic strength of the lower limbs, 6-minute walking test (6MWT, handgrip strength and endurance as secondary outcomes. Body composition was assessed with dual-energy X-ray absorptiometry (DXA and peripheral quantitative computerized tomography (pQCT. The mean difference between the two groups on pre-post change were finally calculated (delta for each outcome. After 8 weeks, there were no significant differences between the groups’ SPPB, handgrip strength or DXA parameters. The group treated with HMB scored significantly better than the control group for PT isokinetic flexion (delta = 1.56±1.56 Nm; p = 0.03 and extension (delta = 3.32±2.61 Nm; p = 0.03, PT isometric strength (delta = 9.74±3.90 Nm; p = 0.02, 6MWT (delta = 7.67±8.29 m; p = 0.04, handgrip endurance (delta = 21.41±16.28 s; p = 0.02, and muscle density assessed with pQCT. No serious adverse effects were reported in either group. In conclusion, a nutritional supplement containing 1.5 g of calcium HMB for 8 weeks in healthy elderly women had no significant effects on SPPB, but did significantly improve several muscle strength and physical performance parameters.ClinicalTrials.gov NCT

  8. 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

  9. Effectiveness of artemether-lumefantrine provided by community health workers in under-five children with uncomplicated malaria in rural Tanzania: an open label prospective study

    Directory of Open Access Journals (Sweden)

    Blessborn Daniel

    2011-03-01

    Full Text Available Abstract Background Home-management of malaria (HMM strategy improves early access of anti-malarial medicines to high-risk groups in remote areas of sub-Saharan Africa. However, limited data are available on the effectiveness of using artemisinin-based combination therapy (ACT within the HMM strategy. The aim of this study was to assess the effectiveness of artemether-lumefantrine (AL, presently the most favoured ACT in Africa, in under-five children with uncomplicated Plasmodium falciparum malaria in Tanzania, when provided by community health workers (CHWs and administered unsupervised by parents or guardians at home. Methods An open label, single arm prospective study was conducted in two rural villages with high malaria transmission in Kibaha District, Tanzania. Children presenting to CHWs with uncomplicated fever and a positive rapid malaria diagnostic test (RDT were provisionally enrolled and provided AL for unsupervised treatment at home. Patients with microscopy confirmed P. falciparum parasitaemia were definitely enrolled and reviewed weekly by the CHWs during 42 days. Primary outcome measure was PCR corrected parasitological cure rate by day 42, as estimated by Kaplan-Meier survival analysis. This trial is registered with ClinicalTrials.gov, number NCT00454961. Results A total of 244 febrile children were enrolled between March-August 2007. Two patients were lost to follow up on day 14, and one patient withdrew consent on day 21. Some 141/241 (58.5% patients had recurrent infection during follow-up, of whom 14 had recrudescence. The PCR corrected cure rate by day 42 was 93.0% (95% CI 88.3%-95.9%. The median lumefantrine concentration was statistically significantly lower in patients with recrudescence (97 ng/mL [IQR 0-234]; n = 10 compared with reinfections (205 ng/mL [114-390]; n = 92, or no parasite reappearance (217 [121-374] ng/mL; n = 70; p ≤ 0.046. Conclusions Provision of AL by CHWs for unsupervised malaria treatment at home

  10. Yokukansan (TJ-54 for treatment of pervasive developmental disorder not otherwise specified and Asperger’s disorder: a 12-week prospective, open-label study

    Directory of Open Access Journals (Sweden)

    Miyaoka Tsuyoshi

    2012-11-01

    Full Text Available Abstract Background Numerous medications have been tested on patients with pervasive developmental disorder not otherwise specified (PDD-NOS and Asperger’s disorder. Although many of these medications have been demonstrated to be useful, no clear primary treatment for PDD-NOS and Asperger’s disorder has emerged. Despite the efficacy of some of the medicines, the acceptability and side effects have proven to be barriers to their use. Recent studies indicate that the traditional Japanese herbal medicine yokukansan (TJ-54 may be safe and useful in treating behavioral and psychological symptoms in dementia and some neuropsychiatric disorders. We aimed at evaluating both the efficacy and safety of TJ-54 in patients with well-defined PDD-NOS and Asperger’s disorder. Methods This was a 12-week prospective, open-label investigation of TJ-54 in 40 children, adolescents, and adults diagnosed with PDD-NOS or Asperger’s disorder. Primary outcome measures included the Clinical Global Impressions-Severity of Illness Scale (CGI-S and the Aberrant Behavior Checklist-Iritability subscale score (ABC-I. Results Forty subjects, ages 8–40 years (mean 22.7 ± 7.3 years received a mean final TJ-54 dosage of 6.4 ± 1.3 g/day (range 2.5-7.5 g/day. Full-scale intelligence quotient (IQ scores ranged from 70 to 110 (mean 88.9 ± 13.2. Thirty-six (90% of 40 subjects showed fewer interfering symptoms of irritability, including aggression, self-injury, and tantrums, with a final CGI-S of 1 or 2 (normal, not at all ill or borderline mentally ill and a 80% or greater improvement on the ABC-I. The mean CGI-S score at baseline was 6.8 ± 0.8 whereas scores at end point was 1.9 ± 0.1 ( Conclusions These preliminary data suggest that TJ-54 may be effective and well tolerated for treatment of severe irritability, lethargy/withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate speech in patients with PDD-NOS or Asperger’s disorder. However

  11. The efficacy and safety of a proprietary onion-pumpkin extract (OPtain120 on blood pressure: an open-label study

    Directory of Open Access Journals (Sweden)

    Orie Yoshinari

    2015-06-01

    Full Text Available Background: Nutraceuticals and functional foods are increasingly being used to help manage hypertension. Treatment with either pumpkin or onion can significantly lower systolic and diastolic blood pressure in animal studies. Traditionally, pumpkin has been used to support healthy blood pressure, glucose tolerance and lipid levels. Onion contains high levels of flavonoids, including quercetin, which decreases blood pressure and promotes restoration of healthy endothelial function. However, human trials on these food sources are limited, and the combined effects of pumpkin and onion have not been examined yet. Objective: We performed an open-label clinical study to evaluate the effects of a proprietary onion-pumpkin extract (OPtain120 on systolic and diastolic blood pressure. Methods: Healthy adults with systolic blood pressure (SBP and diastolic blood pressure (DBP in the elevated range of 140-159 and 80-90 mmHg, respectively, were enrolled in this study. Subjects consumed one capsule of onion-pumpkin extract twice daily for 12 weeks. Daily Home Blood Pressure Measurement (HBPM was taken upon waking and before bed. Office Blood Pressure Measurement (OBPM was taken in-clinic at Week 0, 6, and 12. Results: 52 subjects were screened and 12 were enrolled in the study, with a total of 10 subjects completing the study. Systolic HBPM taken before bed demonstrated a statistically significant reduction from baseline (147.23 mmHg to Week 12 (138.14 mmHg, representing a reduction of 9.09 mmHg (6.17%, p=0.021. Diastolic HBPM taken before bed demonstrated a decrease of 4.06 mmHg (4.46%, p=0.085, a significant reduction from baseline (91.07 mmHg at Week 12 (87.02 mmHg. Non-statistically significant reductions were seen in the early morning Systolic (3.14% and Diastolic (2.57% HBPM and in the Systolic (1.36% OBPM. Conclusion: OPtain120 was safely consumed over a 12-week period. OPtain120 appears to be effective in lowering Systolic Blood Pressure at bedtime in

  12. Bioavailability of everolimus administered as a single 5 mg tablet versus five 1 mg tablets: a randomized, open-label, two-way crossover study of healthy volunteers

    Directory of Open Access Journals (Sweden)

    Thudium K

    2015-01-01

    Full Text Available Karen Thudium,1 Jorge Gallo,2 Emmanuel Bouillaud,2 Carolin Sachs,2 Simantini Eddy,1 Wing Cheung1 1Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 2Novartis Pharma AG, Basel, Switzerland Background: The mammalian target of rapamycin (mTOR inhibitor everolimus has a well-established pharmacokinetics profile. We conducted a randomized, single-center, open-label, two-sequence, two-period crossover study of healthy volunteers to assess the relative bioavailability of everolimus administered as one 5 mg tablet or five 1 mg tablets. Methods: Subjects were randomized 1:1 to receive everolimus dosed as one 5 mg tablet or as five 1 mg tablets on day 1, followed by a washout period on days 8–14 and then the opposite formulation on day 15. Blood sampling for pharmacokinetic evaluation was performed at prespecified time points, with 17 samples taken for each treatment period. Primary variables for evaluation of relative bioavailability were area under the concentration–time curve from time zero to infinity (AUCinf and maximum blood concentration (Cmax. Safety was assessed by reporting the incidence of adverse events (AEs. Results: Twenty-two participants received everolimus as one 5 mg tablet followed by five 1 mg tablets (n=11 or the opposite sequence (n=11. The Cmax of five 1 mg tablets was 48% higher than that of one 5 mg tablet (geometric mean ratio, 1.48; 90% confidence interval [CI], 1.35–1.62. AUCinf was similar (geometric mean ratio, 1.08; 90% CI, 1.02–1.16, as were the extent of absorption and the distribution and elimination kinetics. AEs, all grade 1 or 2, were observed in 54.5% of subjects. Conclusion: Although the extent of absorption was similar, the Cmax of five 1 mg tablets was higher than that of one 5 mg tablet, suggesting these formulations lead to different peak blood concentrations and are not interchangeable at the dose tested. Keywords: absorption kinetics, healthy volunteers

  13. The effects of hyperbaric oxygen therapy on oxidative stress, inflammation, and symptoms in children with autism: an open-label pilot study

    Directory of Open Access Journals (Sweden)

    Melnyk Stepan

    2007-11-01

    worsen oxidative stress and significantly decreased inflammation as measured by CRP levels. Parental observations support anecdotal accounts of improvement in several domains of autism. However, since this was an open-label study, definitive statements regarding the efficacy of HBOT for the treatment of individuals with autism must await results from double-blind, controlled trials. Trial Registration clinicaltrials.gov NCT00324909

  14. The safety and tolerability of vortioxetine: Analysis of data from randomized placebo-controlled trials and open-label extension studies.

    Science.gov (United States)

    Baldwin, David S; Chrones, Lambros; Florea, Ioana; Nielsen, Rebecca; Nomikos, George G; Palo, William; Reines, Elin

    2016-03-01

    The safety and tolerability of vortioxetine in adults with major depressive disorder was assessed. Tolerability was based on the nature, incidence and severity of treatment-emergent adverse events (TEAEs) during acute (6/8) week treatment in 11 randomized, double-blind placebo-controlled short-term studies in major depressive disorder: six with an active reference. Symptoms following discontinuation were assessed through the Discontinuation-Emergent Signs and Symptoms checklist in three studies. Long-term (⩽52 weeks) tolerability was evaluated in five open-label extension studies. Patients (n =5701) were acutely treated with either placebo (n=1817), vortioxetine (5-20mg/day; n=3018), venlafaxine XR (225mg/day; n=113) or duloxetine (60mg/day; n=753). The withdrawal rate due to TEAEs during treatment with vortioxetine (5-20mg/day) was 4.5-7.8%, compared with placebo (3.6%), venlafaxine XR (14.2%) or duloxetine (8.8%). Common TEAEs (incidence ⩾5% and >2 × placebo) with vortioxetine (5-20mg/day) were nausea (20.9-31.2%) and vomiting (2.9-6.5%). For vortioxetine (5-20mg/day), the incidence of TEAEs associated with insomnia was 2.0-5.1% versus 4.0% for placebo, and with sexual dysfunction 1.6-1.8% versus 1.0% for placebo. Discontinuation symptoms as assessed by the mean Discontinuation-Emergent Signs and Symptoms total score after abrupt discontinuation were comparable to placebo in the first and second week. Vortioxetine had no effect relative to placebo on clinical laboratory parameters, body weight, heart rate or blood pressure. Vortioxetine showed no clinically relevant effect on ECG parameters, including the QTcF interval. In long-term treatment, no new types of TEAEs were seen; the mean weight gain was 0.7-0.8kg. Thus, vortioxetine (5-20mg/day) appears safe and generally well tolerated in the treatment of major depressive disorder.

  15. Effects and safety profile of betahistine in patients in the Russian contingent of OSVaLD, an open-label observational study in vestibular vertigo

    Directory of Open Access Journals (Sweden)

    Morozova SV

    2015-01-01

    Full Text Available Svetlana Vyacheslavovna Morozova,1 Natalia Stepanovna Alekseeva,2 Sergey Vasilyevich Lilenko,3 Eduard Ivanovich Matsnev,4 Oleg Anatol'evich Melnikov51Department of Ear, Nose, and Throat, State Budgetary Educational Institution of Higher Professional Training, IM Sechenov First Moscow State Medical University of the Ministry of Healthcare and Social Development of the Russian Federation, Moscow, 2Federal State Budgetary Institution, Scientific Neurology Center of the Russian Academy of Medical Sciences, Moscow, 3St Petersburg Research Institute of Ear, Throat, Nose and Speech, St Petersburg, 4Department of Physiology and Pathology of Auditory and Vestibular Systems, Federal Scientific Center (FSC, Institute for Biomedical Problems, Russian Academy of Sciences (RAS, Moscow, 5ANO Guta Clinic, Moscow, Russian Federation Background: We report here data from the >200 patients recruited in Russia to take part in OSVaLD, a 12-week, open-label, post-marketing surveillance study of the response to betahistine 48 mg/day in vertigo of peripheral vestibular origin carried out in a total of 13 countries.Methods: The primary efficacy endpoint was change in the Dizziness Handicap Inventory (DHI; 100-point scale. Changes in Hospital Anxiety and Depression Scale (HADS and Medical Outcomes Study Short-Form 36, version 2 (SF-36v2® scores were a priori secondary Outcomes.Results: Total DHI score improved by 43 points during betahistine treatment. This aggregate improvement was equally distributed across the three domains of the DHI (physical, emotional, and functional; P<0.0001 for main and subscore changes from baseline. Statistically significant improvements versus baseline were also observed in mean HADS scores for anxiety and depression (both P<0.0001, and in the Physical Component Summary and Mental Component Summary scores of the SF-36v2 (both P<0.0001 versus baseline. Only one suspected adverse drug reaction was recorded in the Russian safety population (n

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  18. 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

  19. Long-Term Efficacy, Safety, and Pharmacokinetics of Drisapersen in Duchenne Muscular Dystrophy: Results from an Open-Label Extension Study

    Science.gov (United States)

    Goemans, Nathalie M.; Tulinius, Már; van den Hauwe, Marleen; Kroksmark, Anna-Karin; Buyse, Gunnar; Wilson, Rosamund J.; van Deutekom, Judith C.; de Kimpe, Sjef J.; Lourbakos, Afrodite; Campion, Giles

    2016-01-01

    Background Drisapersen induces exon 51 skipping during dystrophin pre-mRNA splicing and allows synthesis of partially functional dystrophin in Duchenne muscular dystrophy (DMD) patients with amenable mutations. Methods This 188-week open-label extension of the dose-escalation study assessed the long-term efficacy, safety, and pharmacokinetics of drisapersen (PRO051/GSK2402968), 6 mg/kg subcutaneously, in 12 DMD subjects. Dosing was once weekly for 72 weeks. All subjects had a planned treatment interruption (weeks 73–80), followed by intermittent dosing (weeks 81–188). Results Subjects received a median (range) total dose of 5.93 (5.10 to 6.02) mg/kg drisapersen. After 177 weeks (last efficacy assessment), median (mean [SD]) six-minute walk distance (6MWD) improved by 8 (-24.5 [161]) meters for the 10 subjects able to complete the 6MWD at baseline (mean age [SD]: 9.5 [1.9] years). These statistics include 2 subjects unable to complete the test at later visits and who scored “zero”. When only the 8 ambulant subjects at week 177 were taken into account, a median (mean [SD]) increase of 64 (33 [121]) meters in 6MWD was observed. Of 7 subjects walking ≥330 m at extension baseline, 5 walked farther at week 177. Of 3 subjects walking <330 m, 2 lost ambulation, while 1 declined overall but walked farther at some visits. Over the 188 weeks, the most common adverse events were injection-site reactions, raised urinary α1-microglobulin and proteinuria. Dystrophin expression was detected in all muscle biopsies obtained at week 68 or 72. Conclusion Drisapersen was generally well tolerated over 188 weeks. Possible renal effects, thrombocytopenia and injection-site reactions warrant continued monitoring. Improvements in the 6MWD at 12 weeks were sustained after 3.4 years of dosing for most patients. For a small, uncontrolled study, the outcomes are encouraging, as natural history studies would anticipate a decline of over 100 meters over a 3-year period in a comparable

  20. A randomized open-label trial of on-demand rabeprazole vs ranitidine for patients with non-erosive reflux disease

    Institute of Scientific and Technical Information of China (English)

    Abdallah A Kobeissy; Jana G Hashash; Faek R Jamali; Assaad M Skoury; Reham Haddad; Sarah El-Samad; Rami Ladki

    2012-01-01

    AIM:To compare the efficacy of the proton-pump inhibitor,rabeprazole,with that of the H2-receptor antagonist,ranitidine,as on-demand therapy for relieving symptoms associated with non-erosive reflux disease (NERD).METHODS:This is a single center,prospective,randomized,open-label trial of on-demand therapy with rabeprazole (group A) vs ranitidine (group B) for 4 wk.Eighty-three patients who presented to the American University of Beirut Medical Center with persistent gastroesophageal reflux disease (GERD) symptoms and a normal upper gastrointestinal endoscopy were eligible for the study.Patients in group A (n =44) were allowed a maximum rabeprazole dose of 20 mg twice daily,while those in group B (n =39) were allowed a maximum ranitidine dose of 300 mg twice daily.Efficacy was assessed by patient evaluation of global symptom relief,scores of the SF-36 quality of life (QoL)questionnaires,total number of pills used,and number of medication-free days.RESULTS:Among the 83 patients who were enrolled in the study,76 patients (40 in the rabeprazole group and 36 in the ranitidine group) completed the 4-wk trial.Baseline characteristics were comparable between both groups.After 4 wk,there was no significant difference in the subjective global symptom relief between the rabeprazole and the ranitidine groups (71.4% vs 65.4%,respectively; P =0.9).There were no statistically significant differences between mean cumulative scores of the SF-36 QoL questionnaire for the two study groups (rabeprazole 22.40 ± 27.53 vs ranitidine 17.28 ± 37.06;P =0.582).There was no significant difference in the mean number of pills used (rabeprazole 35.70 ± 29.75vs ranitidine 32.86 ± 26.98; P =0.66).There was also no statistically significant difference in the mean number of medication-free days between both groups.CONCLUSION:Rabeprazole has a comparable efficacy compared to ranitidine when given on-demand for the treatment of NERD.Both medications were associated with improved quality of

  1. Symptomatic or prophylactic treatment of weekend migraine: an open-label, nonrandomized, comparison study of frovatriptan versus naproxen sodium versus no therapy

    Directory of Open Access Journals (Sweden)

    Guidotti M

    2013-01-01

    Full Text Available Mario Guidotti,1 Caterina Barrilà,1 Serena Leva,1 Claudio De Piazza,1 Stefano Omboni21Department of Neurology, Valduce Hospital, Como, 2Italian Institute of Telemedicine, Varese, ItalyBackground: Migraine often occurs during weekends. The efficacy of frovatriptan, naproxen sodium, or no therapy for the acute or prophylactic treatment of weekend migraineurs was tested in an open-label, nonrandomized pilot study.Methods: Twenty-eight subjects (mean age 36 ± 12 years, including 18 females suffering from migraine without aura were followed up for six consecutive weekends. No treatment was administered during the first two weekends. On the third and fourth weekends, patients were given frovatriptan 2.5 mg and on the fifth and sixth weekends naproxen sodium 500 mg. Treatment was taken on Saturday and Sunday morning, regardless of the occurrence of migraine. Efficacy was evaluated through a diary, where patients reported the severity of migraine on a scale from 0 (no migraine to 10 (severe migraine and use of rescue medication.Results: The migraine severity score was significantly lower with frovatriptan (4.8 [95% confidence interval (CI 3.8–5.9] than with naproxen sodium (5.7 [CI 5.1–6.4], P < 0.05 versus frovatriptan or no therapy (6.6 [6.2–7.0], P < 0.01 versus frovatriptan. The difference in favor of frovatriptan was more striking in patients not taking rescue medication (frovatriptan, 1.9 [1.5–2.3] versus naproxen sodium 3.6 [3.0–4.2], P < 0.001 and versus no therapy (5.1 [4.4–5.8], P < 0.001 and on the second day of treatment. The rate of use of rescue medication was significantly (P < 0.05 lower on frovatriptan (12.5% than on naproxen sodium (31.3% or no therapy (56.3%.Conclusion: This pilot study provides the first evidence of the efficacy of a second-generation triptan as symptomatic or prophylactic treatment for weekend migraine.Keywords: migraine, frovatriptan, naproxen sodium, weekend

  2. Acti-Tape™ (elastic therapeutic tape as compared with a knee guard in providing support to the knee joint: an open-label, randomized, crossover study

    Directory of Open Access Journals (Sweden)

    Hui HK

    2014-04-01

    Full Text Available Hoong Keong Hui,1 Narayan J Karne,2 Navneet Sonawane31Nutriworks Ltd, Kowloon, Hong Kong; 2Karne Hospital, Pune, India; 3Vedic Lifesciences Pvt Ltd, Mumbai, IndiaStudy design: Randomized, open-label, crossover, controlled study.Background: Elastic taping methods are used to provide support to the musculoskeletal system in athletes. Acti-Tape™ (an elastic therapeutic tape has been marketed for the last 2–3 years and has shown good results in providing support to the joints. This pilot study was planned to collect data on the clinical outcomes and to assess if a single tape application of Acti-Tape over the knee joint could provide benefits similar to a traditionally used knee guard.Methods: Thirteen subjects aged 30–65 years visiting an orthopedic center in Pune, India who were suffering from osteoarthritis were randomly assigned to either Acti-Tape (n=6 or a knee guard (n=7 in the first intervention period (6 days and were crossed over to the other group in the second intervention period (6 days after a washout of 1 day. Main outcome measures were change from day 0 to day 6 in pain visual analog score (VAS; timed up and go (TUG, medial step down (MSD, and unilateral anterior reach (UAR tests; and subject's preference.Results: Data for all the 13 subjects were pooled and analyzed by Student's t-test as treatment-by-period interaction was not significant by analysis of variance (P>0.05. The changes (mean ± standard deviation after using Acti-Tape and a knee guard, respectively, were pain VAS, –10±5.4 versus (vs –11.5±5.83; TUG, –0.62±1.33 vs –0.46±1.56; UAR, 0.15±1.07 vs 0.75±0.44; and MSD, 1.08±095 vs 0.85±1.14. These were statistically significant with both devices for pain VAS, UAR, and MSD, but not for TUG. Between the treatments however, no statistically significant difference was seen. Eleven of 13 (85% subjects preferred Acti-Tape for future use (P<0.05 by McNemar’s χ2 test. No safety concerns were reported by the

  3. Self-esteem in adolescent patients with attention-deficit/hyperactivity disorder during open-label atomoxetine treatment: psychometric evaluation of the Rosenberg Self-Esteem Scale and clinical findings

    OpenAIRE

    Dittmann, Ralf W.; Wehmeier, Peter M; Schacht, Alexander; Lehmann, Martin; Lehmkuhl, Gerd

    2009-01-01

    To report on (1) psychometric properties of the Rosenberg Self-Esteem Scale (SES) studied in adolescents with ADHD, (2) correlations of SES with ADHD scale scores, and (3) change in patient-reported self-esteem with atomoxetine treatment. ADHD patients (12–17 years), treated in an open-label study for 24 weeks. Secondary analyses on ADHD symptoms (assessed with ADHD-RS, CGI, GIPD scales) and self-esteem (SES) were performed. One hundred and fifty-nine patients were treated. A dichotomous stru...

  4. Differing effects of PTH 1-34, PTH 1-84 and zoledronic acid on bone microarchitecture and estimated strength in postmenopausal women with osteoporosis. An 18 month open-labeled observational study using HR-pQCT

    DEFF Research Database (Denmark)

    Hansen, Stinus; Hauge, Ellen Margrethe; Jensen, Jens-Erik Beck;

    2012-01-01

    Whereas the beneficial effects of intermittent treatment with parathyroid hormone (PTH) (intact PTH 1-84 or fragment PTH 1-34, teriparatide) on vertebral strength is well documented, treatment may not be equally effective in the peripheral skeleton. We used high resolution peripheral quantitative......, n=20) for 18 month in an open label, non-randomized study. A group of postmenopausal osteoporotic women receiving zoledronic acid (5 mg infusion once yearly, n=33) was also included. Anabolic therapy increased cortical porosity in radius (PTH 1-34 32±37%, PTH 1-84 39±32%, both p...

  5. Pharmacokinetics and Bioequivalence of Two Formulations of Febuxostat 40-Mg and 80-Mg Tablets: A Randomized, Open-Label, 4-Way Crossover Study in Healthy Chinese Male Volunteers.

    Directory of Open Access Journals (Sweden)

    Zhu Luo

    Full Text Available The present study aimed to investigate the pharmacokinetic properties of febuxostat in healthy Chinese male volunteers and evaluate whether the two formulations of febuxostat 40-mg and 80-mg tablets are bioequivalent. A randomized, open-label, 4-way crossover study was conducted in healthy Chinese male volunteers under fasting conditions. 24 eligible subjects were randomized in a 1:1:1:1 ratio to receive a single dose of test or reference formulation of febuxostat 40-mg or 80-mg tablet. The washout period between each administration was 1 week. Plasma febuxostat was quantified by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS method. Tolerability was evaluated by monitoring adverse events, physical examinations, 12-lead ECG and laboratory tests. After single-dosing of 1 tablet of 40-mg febuxostat, the pharmacokinetic parameters of test and reference formulations were: Tmax 1.22±0.87 and 1.85±1.03 h, Cmax 1689.16±461.31 and 1613.80±608.43 ng·mL-1, AUC0-t 5139.87±1349.28 and 5517.91±2024.26 ng·mL-1·h, AUC0-∞ 5263.06±1339.16 and 5640.48±2040.22 ng·mL-1·h, t1/2 4.82±2.61 and 4.85±1.78 h, respectively. After single-dosing of 1 tablet of 80-mg febuxostat, the pharmacokinetic parameters of test and reference formulations were: Tmax 1.71±1.21 and 2.23±1.55 h, Cmax 2744.47±1157.44 and 2998.17±1200.13 ng·mL-1, AUC0-t 9634.03±2768.25 and 10467.95±3501.65 ng·mL-1·h, AUC0-∞ 9834.32±2730.51 and 10626.63±3504.08 ng·mL-1·h, t1/2 6.25±2.44 and 5.46±1.65 h, respectively. For single-dosing of 1 tablet of 40-mg febuxostat, 90% CIs for the test/reference ratio of AUC0-t, AUC0-∞ and Cmax were 89.79 to 102.55, 90.14 to 102.56 and 93.99 to 129.63, respectively. For single-dosing of 1 tablet of 80-mg febuxostat, 90% CIs for the test/reference ratio of AUC0-t, AUC0-∞ and Cmax were 86.67 to 100.00, 87.50 to 100.51 and 79.48 to 105.99, respectively. This single dose study revealed similar pharmacokinetic

  6. Diurnal Glycemic Patterns during an 8-Week Open-Label Proof-of-Concept Trial of Empagliflozin in Type 1 Diabetes.

    Directory of Open Access Journals (Sweden)

    Bruce A Perkins

    Full Text Available We recently reported improved glycemic control with reduced insulin dose in subjects with type 1 diabetes treated with the sodium glucose co-transporter-2 inhibitor empagliflozin. To further characterize the effects, we analyzed diurnal glycemic patterns by continuous glucose monitoring (CGM.In an 8-week single-arm open-label pilot study of empagliflozin, we compared ambulatory glucose profiles produced from CGM data during 2-week intervals in a placebo run-in baseline period, end-of-treatment, and post-treatment. Change in glycemic exposure was evaluated by area under the median curve according to time of day (AUCTOTAL 12:00am-11:55pm; AUCDAY 7:05am-10:55pm, AUCNIGHT 11:00pm-7:00am, as well as glycemic variability, glycemic stability and time-in-target (≥70 to ≤140mg/dL.The 40 patients (26 on insulin pump were aged 24±5 years and BMI 24.5±3.2 kg/m2. Consistent with the observed HbA1c decrease (8.0±0.9% to 7.6±0.9%, p<0.0001, normalized AUCTOTAL CGM decreased from 153.7±25.4 to 149.0±30.2mg/dL∙h at end-of-treatment (p = 0.31, and significantly increased post-treatment (164.1±29.5mg/dL∙h, p = 0.02. The numerical decrease in normalized AUCNIGHT (152.0±36.6 to 141.9±34.4mg/dL∙h, p = 0.13 exceeded AUCDAY (154.5±24.5 to 152.6±30.4mg/dL∙h, p = 0.65. Trends toward lower glycemic variability (83.1±18.9 to 75.6±28.6mg/dL, p = 0.06 and little change in glycemic stability (10.8±3.6 to 10.3±4.5mg/dL/h, p = 0.51 were observed. When empagliflozin was discontinued, these worsened relative to baseline (89.3±19.3mg/dL, p = 0.04 and 11.8±3.7mg/dL/hr, p = 0.08. Time-in-target numerically increased (40.2±11.9 to 43.1±13.5%, p = 0.69 at end-of-treatment but reversed post-treatment. Findings were similar on stratification of pump and MDI subjects.We observed that empagliflozin was associated with patterns of improved nighttime glycemia more prominent than daytime.Clinicaltrials.gov NCT01392560.

  7. 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

  8. Open-label comparative clinical study of chlorproguanil-dapsone fixed dose combination (Lapdap alone or with three different doses of artesunate for uncomplicated Plasmodium falciparum malaria.

    Directory of Open Access Journals (Sweden)

    Daniel G Wootton

    Full Text Available UNLABELLED: The objective of this study was to determine the appropriate dose of artesunate for use in a fixed dose combination therapy with chlorproguanil-dapsone (CPG-DDS for the treatment of uncomplicated falciparum malaria. METHODS: Open-label clinical trial comparing CPG-DDS alone or with artesunate 4, 2, or 1 mg/kg at medical centers in Blantyre, Malawi and Farafenni, The Gambia. The trial was conducted between June 2002 and February 2005, including 116 adults (median age 27 years and 107 children (median age 38 months with acute uncomplicated Plasmodium falciparum malaria. Subjects were randomized into 4 groups to receive CPG-DDS alone or plus 4, 2 or 1 mg/kg of artesunate once daily for 3 days. Assessments took place on Days 0-3 in hospital and follow-up on Days 7 and 14 as out-patients. Efficacy was evaluated in the Day 3 per-protocol (PP population using mean time to reduce baseline parasitemia by 90% (PC90. A number of secondary outcomes were also included. Appropriate artesunate dose was determined using a pre-defined decision matrix based on primary and secondary outcomes. Treatment emergent adverse events were recorded from clinical assessments and blood parameters. Safety was evaluated in the intent to treat (ITT population. RESULTS: In the Day 3 PP population for the adult group (N = 85, mean time to PC90 was 19.1 h in the CPG-DDS group, significantly longer than for the +artesunate 1 mg/kg (12.5 h; treatment difference -6.6 h [95%CI -11.8, -1.5], 2 mg/kg (10.7 h; -8.4 h [95%CI -13.6, -3.2] and 4 mg/kg (10.3 h; -8.7 h [95%CI -14.1, -3.2] groups. For children in the Day 3 PP population (N = 92, mean time to PC90 was 21.1 h in the CPG-DDS group, similar to the +artesunate 1 mg/kg group (17.7 h; -3.3 h [95%CI -8.6, 2.0], though the +artesunate 2 mg/kg and 4 mg/kg groups had significantly shorter mean times to PC90 versus CPG-DDS; 14.4 h (treatment difference -6.4 h [95%CI -11.7, -1.0] and 12.8 h (-7.4 h [95%CI -12.9, -1

  9. Effects of flurbiprofen and tiaprofenic Acid on oxidative stress markers in osteoarthritis: A prospective, randomized, open-label, active- and placebo-controlled trial

    Science.gov (United States)

    Tuzun, Sansin; Uzun, Hafize; Aydin, Seval; Dinc, Ahmet; Sipahi, Sevtap; Topcuoglu, Mehmet Ata; Yucel, Rifat; Belce, Ahmet

    2005-01-01

    Background: The relationship between oxidative stress and osteoarthritis (OA) has been widely investigated. Serum malondialdehyde (MDA), nitric oxide (NO), and Cu/Zn superoxide dismutase (SOD) levels are useful markers of oxidative stress. Because of the importance of oxidative stress markers in the pathogenesis of OA, treatment might involve modification of these markers to control oxidative stress. Objective: The aim of this study was to compare the effects of 2 conventionalNSAIDs on markers of oxidative stress in patients with OA of the knee. Methods: This 3-week, prospective, randomized, open-label, active- and placebo-controlled study was conducted at the Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey. Adult patients with clinically and radiographically diagnosed moderate OA of the knee who were previously untreated were enrolled. Patients were randomly assigned to 1 of 3 treatment groups: flurbiprofen 100 mg PO (tablets) BID, tiaprofenic acid 300 mg PO (tablets) BID, or placebo tablets BID. Patients were evaluated using clinical assessment and laboratory testing before treatment (week 0; baseline) and at the end of week 3. The primary end points were the differences in serum MDA, NO, and SOD levels versus placebo. Clinical parameters-pain at rest and on motion-were evaluated using a 10-cm visual analog scale (0 = no pain to 10 = worst pain imaginable). The duration (in minutes) of morning stiffness was recorded by patients, using patient diaries. The differences between treatment groups were assessed using multivariate analysis. Results: Thirty-nine patients (20 women, 19 men; mean [SD] age, 59.0 [11.3]years) were included in the study. Mean serum MDA and NO levels were significantly decreased at 3 weeks compared with baseline in the 2 active-treatment groups (all, P < 0.001); these values remained statistically similar to baseline in the placebo group. Serum SOD levels were increased significantly from baseline in the 2 active

  10. Different dose combinations of bortezomib and dexamethasone in the treatment of relapsed or refractory myeloma: an open-label,observational, multi-center study in China

    Institute of Scientific and Technical Information of China (English)

    YUAN Zhen-gang; JIN Jie; HUANG Xiao-jun; LI Yan; CHEN Wen-ming; LIU Zhuo-gang; CHEN Xie-qun; SHEN Zhi-xiang; HOU Jian

    2011-01-01

    Background Although previous clinical study revealed that bortezomib combined with dexamethasone had improved the outcomes of relapsed or refractory multiple myeloma (RRMM), the optimal dose combinations of bortezomib and dexamethasone remain unknown. This trial aimed to observe the efficacy and safety of different dose combinations of bortezomib and dexamethasone in the treatment of RRMM patients in China.Methods A total of 168 patients with relapsed multiple myeloma (MM) who were refractory to at lest two prior treatments were enrolled in this multicenter, open-label, non-randomized, prospective clinical trial. Twenty patients received 1.3 mg/m2 of bortezomib twice weekly for 2 weeks of a 3-week cycle for up to 8 cycles and oral or intravenous dexamethasone 20 mg on the day of and after each bortezomib dose (group 1); 66 patients received less than 1.3 mg/m2(0.7-1.0 mg/m2) of bortezomib and dexamethasone 20 mg on the same schedule (group 2); 37 patients received 1.3 mg/m2 of bortezomib and dexamethasone 40 mg (group 3) and 45 patients received less than 1.3 mg/m2 (0.7-1.0 mg/m2)of bortezomib and dexamethasone 40 mg (group 4). The response was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation and confirmed by an independent review committee. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria, version 3.0. Results The median age of groups 1 to 4 was 61,62, 56, and 60 years, respectively. Most patients were in stages Ⅱ/Ⅲ of MM and the most common subtype was IgG The rate of overall response to bortezomib and dexamethasone of group 1 to 4 was 72.2% (13/18), 73.8% (48/65), 78.8% (26/33) and 78.0% (32/41) (P=0.91), including a complete response rate of 22.2% (4/18), 20.0% (13/65), 33.3% (11/33) and 29.3% (12/41) (P=0.67), respectively. There was no statistical significance in time to progression and overall survival among these 4 groups (P >0.05). The most

  11. Eggshell membrane: A possible new natural therapeutic for joint and connective tissue disorders. Results from two open-label human clinical studies

    Directory of Open Access Journals (Sweden)

    Kevin J Ruff

    2009-05-01

    Full Text Available Kevin J Ruff1, Dale P DeVore2, Michael D Leu3, Mark A Robinson41ESM Technologies, LLC, Carthage, MO, USA; 2Membrell, LLC, Carthage, MO, USA; 3Private Practice, Jenks, OK, USA; 4Robinson Family Health Center, Carthage, MO, USABackground: Natural Eggshell Membrane (NEM® is a novel dietary supplement that contains naturally occurring glycosaminoglycans and proteins essential for maintaining healthy joint and connective tissues. Two single center, open-label human clinical studies were conducted to evaluate the efficacy and safety of NEM® as a treatment for pain and inflexibility associated with joint and connective tissue disorders. Methods: Eleven (single-arm trial and 28 (double-arm trial patients received oral NEM® 500 mg once daily for four weeks. The primary outcome measure was to evaluate the change in general pain associated with the treatment joints/areas (both studies. In the single-arm trial, range of motion (ROM and related ROM-associated pain was also evaluated. The primary treatment response endpoints were at seven and 30 days. Both clinical assessments were performed on the intent-to-treat (ITT population within each study.Results: Single-arm trial: Supplementation with NEM® produced a significant treatment response at seven days for flexibility (27.8% increase; P = 0.038 and at 30 days for general pain (72.5% reduction; P = 0.007, flexibility (43.7% increase; P = 0.006, and ROM-associated pain (75.9% reduction; P = 0.021. Double-arm trial: Supplementation with NEM® produced a significant treatment response for pain at seven days for both treatment arms (X: 18.4% reduction; P = 0.021. Y: 31.3% reduction; P = 0.014. There was no clinically meaningful difference between treatment arms at seven days, so the Y arm crossed over to the X formulation for the remainder of the study. The significant treatment response continued through 30 days for pain (30.2% reduction; P = 0.0001. There were no adverse events reported during either

  12. 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...

  13. Open-Label Study of the Influence of Food Containing the Royal Sun Mushroom, Agaricus brasiliensis KA21 (Higher Basidiomycetes), on the Quality of Life of Healthy Human Volunteers.

    Science.gov (United States)

    Motoi, Masuro; Motoi, Akitomo; Yamanaka, Daisuke; Ohno, Naohito

    2015-01-01

    We conducted an open-label study in which food containing Agaricus brasiliensis KA21 was consumed continuously for 12 weeks. A questionnaire for subjective evaluation of the efficacy of this food (hereafter, subjective evaluation questionnaire) revealed significant improvements compared with before its intake; there were improvements in the scores of the amounts of hair loss and gray hair, fatigue and general malaise, eye strain, shoulder stiffness, coldness of extremities, difficulty staying awake during the day, and ease of getting out of bed. These findings suggest that intake of food containing A. brasiliensis KA21 results in the above-mentioned subjectively evaluated improvements, and the possibility that A. brasiliensis KA21 improves the body's immunity. Moreover, no issues regarding the safety of the test food were found. PMID:26756293

  14. Strong Correlation Between Concentrations of Tenofovir (TFV) Emtricitabine (FTC) in Hair and TFV Diphosphate and FTC Triphosphate in Dried Blood Spots in the iPrEx Open Label Extension: Implications for Pre-exposure Prophylaxis Adherence Monitoring.

    Science.gov (United States)

    Gandhi, Monica; Glidden, David V; Liu, Albert; Anderson, Peter L; Horng, Howard; Defechereux, Patricia; Guanira, Juan V; Grinsztejn, Beatriz; Chariyalertsak, Suwat; Bekker, Linda-Gail; Grant, Robert M

    2015-11-01

    Self-reported adherence to pre-exposure prophylaxis (PrEP) has limitations, raising interest in pharmacologic monitoring. Drug concentrations in hair and dried blood spots (DBS) are used to assess long-term-exposure; hair shipment/storage occurs at room temperature. The iPrEx Open Label Extension collected DBS routinely, with opt-in hair collection; concentrations were measured with liquid chromatography/tandem mass spectrometry. In 806 hair-DBS pairs, tenofovir (TFV) hair levels and TFV diphosphate (DP) in DBS were strongly correlated (Spearman coefficient r = 0.734; P hair TFV/DBS emtricitabine (FTC) triphosphate (TP) (r = 0.781; P hair FTC/DBS TFV-DP (r = 0.74; P hair FTC/DBS FTC-TP (r = 0.587; P Hair TFV/FTC concentrations correlate strongly with DBS levels, which are predictive of PrEP outcomes.

  15. [The results of Russian multicenter open-label observational study of the efficacy and safety of мelaxen (melatonin) for the treatment of disordered sleep in patients with chronic cerebral ischemia].

    Science.gov (United States)

    Poluéktov, M G; Levin, Ia I; Boĭko, A N; Skoromets, A A; Bel'skaia, G N; Gustov, A V; Doronin, B M; Poverennova, I E; Spirin, N N; Iakupov, E Z

    2012-01-01

    The results of the multicenter open-label observational study of the efficacy and safety of the Melaxen (melatonin) for the treatment of disordered sleep in patients with chronic cerebral ischemia are presented. 2062 patients were studied with the use of subjective psychometric scales: subjective sleep characteristics scale, sleep apnea screening questionnaire, Epworth sleepiness scale, hospital anxiety and depression scale. Mean age of patients was 55.7±9.0 years, there were 74.1% females and 25.9% males. Melaxen was given in dosage of 3 mg. before sleep for 24 days. The use of Melaxen leads to the increase of subjective sleep quality by the subjective sleep characteristics scale from 19.7±3.1 points to и 22.7±3.4 points on day 14 and 22.7±3.4 on day 24 (differences are significant at pinsomnia treatment in patients with chronic cerebral ischemia. PMID:23235408

  16. Effects of a Facial Cream Containing the Minor Alkaloid Anatabine on Improving the Appearance of the Skin in Mild to Moderate Rosacea: An Open-Label Case Series Study

    Directory of Open Access Journals (Sweden)

    Ryan K. Lanier

    2013-11-01

    Full Text Available Background: Current medical and scientific research indicates that rosacea, a chronic and often debilitating skin condition that primarily affects the central face, may be caused by an overactive or excessive inflammatory immune response. Regardless of etiology, the accompanying redness and inflammation is unsightly and difficult for the patient. Anatabine is an alkaloid from the plant family Solanaceae that has been shown in several preclinical studies to modulate proinflammatory signaling pathways. Objective: A cream containing anatabine was developed and evaluated in an open-label case series study for safety and effects on the appearance of the skin in 10 patients with mild to moderate rosacea. Methods: Patients applied the cream to the face twice daily for a period of 30 days. Patients and the study physician completed safety and efficacy assessments at study end. Results: Results showed that 50% of the patients self-reported improvement in the appearance of their skin, and the physician noted improvement in 70% of the patients. Photographs taken before and after 30 days of cream use provide visual evidence of the improvement in several patients. There were no complications or adverse events reported by any of the patients in the study, indicating that the anatabine cream was safe and very well tolerated. Conclusion: The results of this open-label case series show that a facial cream containing anatabine can improve the appearance of the skin in patients with mild to moderate rosacea and suggest that a double-blind, vehicle-controlled trial in a larger number of subjects is warranted.

  17. Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the phase 3 BENEFIT trial

    DEFF Research Database (Denmark)

    Kappos, Ludwig; Freedman, Mark S; Polman, Chris H;

    2009-01-01

    beta-1b 250 microg (n=292; early treatment) or placebo (n=176; delayed treatment) subcutaneously every other day for 2 years, or until diagnosis of CDMS. All patients were then eligible to enter a prospectively planned follow-up phase with open-label interferon beta-1b up to a maximum of 5 years after...

  18. Congenital multifocal osteomyelitis at 24 weeks' gestation

    Energy Technology Data Exchange (ETDEWEB)

    Raupp, Peter; Shubbar, Adil; Baichoo, Vijaymani; Samson, Gregory [Al Corniche Hospital, Department of Neonatology, P.O. Box 3788, Abu Dhabi (United Arab Emirates)

    2007-12-15

    We report an extremely rare case of congenital nonsyphilitic osteomyelitis in a very preterm infant, providing a unique illustration of the radiological appearances at birth, which may serve as a reference to facilitate diagnosis. (orig.)

  19. The safety and effectiveness of open-label extended-release carbamazepine in the treatment of children and adolescents with bipolar I disorder suffering from a manic or mixed episode

    Directory of Open Access Journals (Sweden)

    Findling RL

    2014-08-01

    Full Text Available Robert L Findling,1,2 Lawrence D Ginsberg31Division of Child and Adolescent Psychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, 2Kennedy Krieger Institute, Baltimore, MD, USA; 3Red Oak Psychiatry Associates, PA, Houston, TX, USAObjective: To assess the safety and effectiveness of open-label treatment with extended-release carbamazepine (ERC in pediatric subjects suffering from bipolar I disorder.Method: Medically healthy youths aged 10–17 years suffering from an acute manic or mixed episode were eligible. After screening for study eligibility, the youths began a 5-week titration period in which doses of ERC were adjusted in order to optimize benefit whilst minimizing adverse events, at doses between 200–1,200 mg/day. Thereafter, subjects could continue to receive treatment during a subsequent 21-week period. Safety measures included spontaneously reported adverse events (AEs and laboratory assessments. The primary efficacy measure was the Young Mania Rating Scale (YMRS.Results: A total of 60 children (ages 10–12 and 97 adolescents (ages 13–17, with an overall average age of 13.4 years (standard deviation [SD] 2.0 years received ERC. The mean duration of study participation was 109.6 days (SD 70.2 days, with 66 (42% completing the entire study. At end of study participation (end point, the most prevalent dose of ERC was 1,200 mg: 31.7% of children and 24.7% of adolescents reached the 1,200 mg dose. The YMRS decreased from a mean of 28.6 (SD 6.2 at baseline to a mean of 13.8 (SD 9.4 (P<0.0001 at end point. A total of 26 subjects discontinued study participation because of AEs, the most common of which were rash (n=6, white blood cell count decreased (n=5, nausea (n=3, and vomiting (n=3. No deaths were reported. The most commonly reported AEs were headache (n=41, somnolence (n=30, nausea (n=22, dizziness (n=21, and fatigue (n=19.Conclusions: Open-label administration of ERC might be a safe

  20. Safety and immunogenicity of the DTP/HB /Hib combination vaccine: phase I study

    OpenAIRE

    Kusnandi Rusmil; Eddy Fadlyana; Novilia Sjafri Bachtiar; Hadyana

    2013-01-01

    Background The World Health Organization (WHO) has recommended the introduction of hepatitis B (HB) and Haemophilus influenza type b (Hib) vaccines into routine childhood vaccination programs. A new diptheria/tetanus/pertussis (DTP)/hepatitis B/Hib pentavalent combination vaccine has been developed. Objective To evaluate the safety and immunogenicity of a new combination DTP/HB/Hib liquid vaccine in infants. Methods An open-label, uncontrolled, prospective intervention phase I study w...

  1. 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.

  2. Vagus nerve stimulation therapy: 2-year prospective open-label study of 40 subjects with refractory epilepsy and low IQ who are living in long-term care facilities.

    Science.gov (United States)

    Huf, Roger L; Mamelak, Adam; Kneedy-Cayem, Kara

    2005-05-01

    Treating seizures among patients with mental retardation/developmental disabilities (MR/DD) is difficult owing in large part to the presence of additional comorbidities and the resulting need for polytherapy. Therefore, a nonpharmacological treatment option is needed for this population. This prospective, open-label study documented the long-term outcome of 40 low-IQ (<70) patients living in long-term care facilities who received vagus nerve stimulation (VNS) therapy for pharmacoresistant epilepsy. Subjects were seen every 1 to 3 months by their neurologist (R.H.). Seizure frequency, antiepileptic medication, and quality-of-life information were documented preimplantation and quarterly thereafter through 2 years. The surgery and therapy were well tolerated. Seizures were reduced by at least 50% for 11 subjects. Antiepileptic medications were reduced from 3.3 per subject at baseline to an average of 2.3 per subject after 2 years. According to caregiver reports, overall quality of life improved for the majority of subjects; also, using the Client Development Evaluation Report (CDER), statistically significant improvements were reported at both 1 and 2 years in attention span, word usage, clarity of speech, standing balance, washing dishes, and household chores. VNS is a viable treatment option for low-IQ patients with pharmacoresistant epilepsy who are living in long-term care facilities. PMID:15820352

  3. Efficacy and Safety of Oral Lactoferrin Supplementation in Combination with rHuEPO-β for the Treatment of Anemia in Advanced Cancer Patients Undergoing Chemotherapy: Open-Label, Randomized Controlled Study

    Science.gov (United States)

    Madeddu, Clelia; Gramignano, Giulia; Mulas, Carlo; Sanna, Eleonora; Mantovani, Giovanni

    2010-01-01

    Advanced-stage cancer patients often suffer from anemia that closely resembles the anemia of chronic inflammatory diseases characterized by specific changes in iron homeostasis and absorption. i.v. iron improves the efficacy of recombinant human erythropoietin (rHuEPO) in anemic cancer patients undergoing chemotherapy. We report the results of an open-label, randomized, prospective trial aimed at testing the efficacy and safety of treatment with oral lactoferrin versus i.v. iron, both combined with rHuEPO, for the treatment of anemia in a population of 148 advanced cancer patients undergoing chemotherapy. All patients received s.c. rHuEPO-β, 30,000 UI once weekly for 12 weeks, and were randomly assigned to ferric gluconate (125 mg i.v. weekly) or lactoferrin (200 mg/day). Both arms showed a significant hemoglobin increase. No difference in the mean hemoglobin increase or the hematopoietic response, time to hematopoietic response, or mean change in serum iron, C-reactive protein, or erythrocyte sedimentation rate were observed between arms. In contrast, ferritin decreased in the lactoferrin arm whereas it increased in the i.v. iron arm. In conclusion, these results show similar efficacy for oral lactoferrin and for i.v. iron, combined with rHuEPO, for the treatment of anemia in advanced cancer patients undergoing chemotherapy. PMID:20647390

  4. Strong Correlation Between Concentrations of Tenofovir (TFV) Emtricitabine (FTC) in Hair and TFV Diphosphate and FTC Triphosphate in Dried Blood Spots in the iPrEx Open Label Extension: Implications for Pre-exposure Prophylaxis Adherence Monitoring

    Science.gov (United States)

    Gandhi, Monica; Glidden, David V.; Liu, Albert; Anderson, Peter L.; Horng, Howard; Defechereux, Patricia; Guanira, Juan V.; Grinsztejn, Beatriz; Chariyalertsak, Suwat; Bekker, Linda-Gail; Grant, Robert M.

    2015-01-01

    Self-reported adherence to pre-exposure prophylaxis (PrEP) has limitations, raising interest in pharmacologic monitoring. Drug concentrations in hair and dried blood spots (DBS) are used to assess long-term-exposure; hair shipment/storage occurs at room temperature. The iPrEx Open Label Extension collected DBS routinely, with opt-in hair collection; concentrations were measured with liquid chromatography/tandem mass spectrometry. In 806 hair-DBS pairs, tenofovir (TFV) hair levels and TFV diphosphate (DP) in DBS were strongly correlated (Spearman coefficient r = 0.734; P < .001), as were hair TFV/DBS emtricitabine (FTC) triphosphate (TP) (r = 0.781; P < .001); hair FTC/DBS TFV-DP (r = 0.74; P < .001); hair FTC/DBS FTC-TP (r = 0.587; P < .001). Drug detectability was generally concordant by matrix. Hair TFV/FTC concentrations correlate strongly with DBS levels, which are predictive of PrEP outcomes. PMID:25895984

  5. A Prospective, Open-label Study to Compare the Efficacy and the Safety of Topical Loteprednol Etabonate and Topical Flurbiprofen Sodium in Patients with Post-Operative Inflammation after Cataract Extraction

    Science.gov (United States)

    Bannale, Sheshidhar G.; Pundarikaksha, H.P.; Sowbhagya, H.N.

    2012-01-01

    Purpose To study the effect of the topical Non-Steroidal Anti Inflammatory Drug (NSAID), Flurbiprofen 0.03%, as an alternative to the topical steroids for the postoperative control of inflammation in cataract surgeries. Methods The effect of the topical NSAID, flurbiprofen sodium 0.03%, was studied and compared with that of the topical steroid – Loteprednol etabonate 0.5% suspension (as eye drops) in a prospective, open labelled study. Both the groups (20 patients each) were similar in the baseline parameters. The postoperative inflammatory response following the standard, small incision, extra capsular cataract extraction was assessed in both the groups for 28 post-operative days. The parameters which were considered for the study were conjunctival hyperaemia, ciliary congestion, corneal oedema, cells in the anterior chamber, aqueous flare and ocular pain. The severity of the postoperative inflammatory responses for both the drugs was graded on the post-operative days 1, 7, 14, 21 and 28 and it was statistically analyzed. Results The 2 groups did not differ statistically in the effect of the treatment for any of the variables, which included aqueous cells, flare, ciliary congestion and conjunctival congestion (p< 0.001). Both the drugs were well tolerated and no severe adverse Drug Reactions (ADRs) were caused by the topical NSAID and the topical steroid. Conclusion The topical NSAID, Flurbiprofen, is as effective as the topical corticosteroid, Loteprednol and it can be used as an alternative in the routine postoperative treatment following uncomplicated cataract surgeries. PMID:23285440

  6. Effects of an ethyl lactate shampoo in conjunction with a systemic antibiotic in the treatment of canine superficial bacterial pyoderma in an open-label, nonplacebo-controlled study.

    Science.gov (United States)

    de Jaham, Caroline

    2003-01-01

    An open-label, nonplacebo-controlled study was designed to compare systemic cephalexin therapy versus systemic cephalexin and ethyl lactate shampoo therapy in the treatment of canine superficial bacterial pyoderma. Twenty client-owned dogs diagnosed with generalized superficial bacterial pyoderma (SP) were alternately assigned to oral treatment with cephalexin (25 to 30 mg/kg every 12 hours) or treatment with cephalexin (as for Group 1) and twice-weekly shampooing with a 10% ethyl lactate shampoo, which was left in contact with the dog's skin for 10 minutes. On Days 14 and 28, skin lesion severity scores, assessed by the investigators, were significantly (P shampoo than for the group treated with cephalexin only. On Day 14, dog owners gave better scores to dogs treated with cephalexin and shampoo for haircoat appearance and body odor than for dogs treated only with cephalexin. Clinical and cytologic resolution of SP occurred significantly (P shampoo group (29.4 days) than in the cephalexin only group (37.8 days).

  7. Effects of an ethyl lactate shampoo in conjunction with a systemic antibiotic in the treatment of canine superficial bacterial pyoderma in an open-label, nonplacebo-controlled study.

    Science.gov (United States)

    de Jaham, Caroline

    2003-01-01

    An open-label, nonplacebo-controlled study was designed to compare systemic cephalexin therapy versus systemic cephalexin and ethyl lactate shampoo therapy in the treatment of canine superficial bacterial pyoderma. Twenty client-owned dogs diagnosed with generalized superficial bacterial pyoderma (SP) were alternately assigned to oral treatment with cephalexin (25 to 30 mg/kg every 12 hours) or treatment with cephalexin (as for Group 1) and twice-weekly shampooing with a 10% ethyl lactate shampoo, which was left in contact with the dog's skin for 10 minutes. On Days 14 and 28, skin lesion severity scores, assessed by the investigators, were significantly (P shampoo than for the group treated with cephalexin only. On Day 14, dog owners gave better scores to dogs treated with cephalexin and shampoo for haircoat appearance and body odor than for dogs treated only with cephalexin. Clinical and cytologic resolution of SP occurred significantly (P shampoo group (29.4 days) than in the cephalexin only group (37.8 days). PMID:12756640

  8. Effects of a One Year Reusable Contraceptive Vaginal Ring on Vaginal Microflora and the Risk of Vaginal Infection: An Open-Label Prospective Evaluation.

    Directory of Open Access Journals (Sweden)

    Yongmei Huang

    Full Text Available A contraceptive vaginal ring (CVR containing Nestorone® (NES and ethinyl estradiol (EE that is reusable for 1- year (13 cycles is under development. This study assessed effects of this investigational CVR on the incidence of vaginal infections and change in vaginal microflora.There were 120 women enrolled into a NES/EE CVR Phase III trial and a microbiology sub-study for up to 1- year of cyclic product use. Gynecological examinations were conducted at baseline, the first week of cycle 6 and last week of cycle 13 (or during early discontinuation visits. Vaginal swabs were obtained for wet mount microscopy, Gram stain and culture. The CVR was removed from the vagina at the last study visit and cultured. Semi-quantitative cultures for Lactobacillus, Gardnerella vaginalis, Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, anaerobic gram negative rods (GNRs, Candida albicans and other yeasts were performed on vaginal and CVR samples. Vaginal infections were documented throughout the study.Over 1- year of use, 3.3% of subjects were clinically diagnosed with bacterial vaginosis, 15.0% with vulvovaginal candidiasis, and 0.8% with trichomoniasis. The detection rate of these three infections did not change significantly from baseline to either Cycle 6 or 13. Nugent scores remained stable. H2O2-positive Lactobacillus dominated vaginal flora with a non-significant prevalence increase from 76.7% at baseline to 82.7% at cycle 6 and 90.2% at cycle 13, and a median concentration of 107 colony forming units (cfu per gram. Although anaerobic GNRs prevalence increased significantly, the median concentration decreased slightly (104 to 103cfu per gram. There were no significant changes in frequency or concentrations of other pathogens. High levels of agreement between vaginal and ring surface microbiota were observed.Sustained use of the NES/EE CVR did not increase the risk of vaginal infection and was not disruptive to the vaginal ecosystem

  9. Craving decrease with topiramate in outpatient treatment for cocaine dependence: an open label trial Diminuição da fissura com topiramato no tratamento ambulatorial para dependência de cocaína: um ensaio clínico aberto

    OpenAIRE

    Alessandra Diehl Reis; Luiz André Castro; Roberta Faria; Ronaldo Laranjeira

    2008-01-01

    OBJECTIVE: To evaluate anticraving action and tolerability of topiramate in cocaine user treatment. METHOD: Male users of inhaled cocaine which met criteria for cocaine dependence (Diagnostic and Statistical Manual of Mental Disorders, fourth edition) were selected for outpatient 12-week, open label trial with topiramate; individual dosage ranged between 25-300 mg/day. Main clinical variables were abstinence rate, craving intensity, frequency and duration, adherence, dropouts, side effects an...

  10. Scheduled Intermittent Screening with Rapid Diagnostic Tests and Treatment with Dihydroartemisinin-Piperaquine versus Intermittent Preventive Therapy with Sulfadoxine-Pyrimethamine for Malaria in Pregnancy in Malawi: An Open-Label Randomized Controlled Trial

    Science.gov (United States)

    Madanitsa, Mwayiwawo; Kalilani, Linda; Mwapasa, Victor; van Eijk, Anna M.; Khairallah, Carole; Ali, Doreen; Pace, Cheryl; Smedley, James; Thwai, Kyaw-Lay; Levitt, Brandt; Kang’ombe, Arthur; Faragher, Brian; Taylor, Steve M.; Meshnick, Steve; ter Kuile, Feiko O.

    2016-01-01

    Background In Africa, most plasmodium infections during pregnancy remain asymptomatic, yet are associated with maternal anemia and low birthweight. WHO recommends intermittent preventive therapy in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP). However, sulfadoxine-pyrimethamine (SP) efficacy is threatened by high-level parasite resistance. We conducted a trial to evaluate the efficacy and safety of scheduled intermittent screening with malaria rapid diagnostic tests (RDTs) and treatment of RDT-positive women with dihydroartemisinin-piperaquine (DP) as an alternative strategy to IPTp-SP. Methods and Findings This was an open-label, two-arm individually randomized superiority trial among HIV-seronegative women at three sites in Malawi with high SP resistance. The intervention consisted of three or four scheduled visits in the second and third trimester, 4 to 6 wk apart. Women in the IPTp-SP arm received SP at each visit. Women in the intermittent screening and treatment in pregnancy with DP (ISTp-DP) arm were screened for malaria at every visit and treated with DP if RDT-positive. The primary outcomes were adverse live birth outcome (composite of small for gestational age, low birthweight [<2,500 g], or preterm birth [<37 wk]) in paucigravidae (first or second pregnancy) and maternal or placental plasmodium infection at delivery in multigravidae (third pregnancy or higher). Analysis was by intention to treat. Between 21 July 2011 and 18 March 2013, 1,873 women were recruited (1,155 paucigravidae and 718 multigravidae). The prevalence of adverse live birth outcome was similar in the ISTp-DP (29.9%) and IPTp-SP (28.8%) arms (risk difference = 1.08% [95% CI −3.25% to 5.41%]; all women: relative risk [RR] = 1.04 [95% CI 0.90–1.20], p = 0.625; paucigravidae: RR = 1.10 [95% CI 0.92–1.31], p = 0.282; multigravidae: RR = 0.92 [95% CI 0.71–1.20], p = 0.543). The prevalence of malaria at delivery was higher in the ISTp-DP arm (48.7% versus 40.8%; risk difference

  11. 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)

  12. A randomized, open-label, comparative efficacy trial of artemether-lumefantrine suspension versus artemether-lumefantrine tablets for treatment of uncomplicated Plasmodium falciparum malaria in children in western Kenya

    Directory of Open Access Journals (Sweden)

    Akhwale Willis S

    2008-12-01

    Full Text Available Abstract Background Artemether/lumefantrine (AL has been adopted as the treatment of choice for uncomplicated malaria in Kenya and other countries in the region. Six-dose artemether/lumefantrine tablets are highly effective and safe for the treatment of infants and children weighing between five and 25 kg with uncomplicated Plasmodium falciparum malaria. However, oral paediatric formulations are urgently needed, as the tablets are difficult to administer to young children, who cannot swallow whole tablets or tolerate the bitter taste of the crushed tablets. Methods A randomized, controlled, open-label trial was conducted comparing day 28 PCR corrected cure-rates in 245 children aged 6–59 months, treated over three days with either six-dose of artemether/lumefantrine tablets (Coartem® or three-dose of artemether/lumefantrine suspension (Co-artesiane® for uncomplicated falciparum malaria in western Kenya. The children were followed-up with clinical, parasitological and haematological evaluations over 28 days. Results Ninety three percent (124/133 and 90% (121/134 children in the AL tablets and AL suspension arms respectively completed followed up. A per protocol analysis revealed a PCR-corrected parasitological cure rate of 96.0% at Day 28 in the AL tablets group and 93.4% in the AL suspension group, p = 0.40. Both drugs effectively cleared gametocytes and were well tolerated, with no difference in the overall incidence of adverse events. Conclusion The once daily three-dose of artemether-lumefantrine suspension (Co-artesiane® was not superior to six-dose artemether-lumefantrine tablets (Coartem® for the treatment of uncomplicated malaria in children below five years of age in western Kenya. Trial registration ClinicalTrials.gov NCT00529867

  13. Multicentre, prospective, randomised, open-label, blinded end point trial of the efficacy of allopurinol therapy in improving cardiovascular outcomes in patients with ischaemic heart disease: protocol of the ALL-HEART study

    Science.gov (United States)

    Ford, Ian; Walker, Andrew; Hawkey, Chris; Begg, Alan; Avery, Anthony; Taggar, Jaspal; Wei, Li; Struthers, Allan D; MacDonald, Thomas M

    2016-01-01

    Introduction Ischaemic heart disease (IHD) is one of the most common causes of death in the UK and treatment of patients with IHD costs the National Health System (NHS) billions of pounds each year. Allopurinol is a xanthine oxidase inhibitor used to prevent gout that also has several positive effects on the cardiovascular system. The ALL-HEART study aims to determine whether allopurinol improves cardiovascular outcomes in patients with IHD. Methods and analysis The ALL-HEART study is a multicentre, controlled, prospective, randomised, open-label blinded end point (PROBE) trial of allopurinol (up to 600 mg daily) versus no treatment in a 1:1 ratio, added to usual care, in 5215 patients aged 60 years and over with IHD. Patients are followed up by electronic record linkage and annual questionnaires for an average of 4 years. The primary outcome is the composite of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary outcomes include all-cause mortality, quality of life and cost-effectiveness of allopurinol. The study will end when 631 adjudicated primary outcomes have occurred. The study is powered at 80% to detect a 20% reduction in the primary end point for the intervention. Patient recruitment to the ALL-HEART study started in February 2014. Ethics and dissemination The study received ethical approval from the East of Scotland Research Ethics Service (EoSRES) REC 2 (13/ES/0104). The study is event-driven and results are expected after 2019. Results will be reported in peer-reviewed journals and at scientific meetings. Results will also be disseminated to guideline committees, NHS organisations and patient groups. Trial registration number 32017426, pre-results. PMID:27609859

  14. Multicentre open-label randomised controlled trial to compare colistin alone with colistin plus meropenem for the treatment of severe infections caused by carbapenem-resistant Gram-negative infections (AIDA): a study protocol

    Science.gov (United States)

    Dickstein, Yaakov; Leibovici, Leonard; Yahav, Dafna; Eliakim-Raz, Noa; Daikos, George L; Skiada, Anna; Antoniadou, Anastasia; Carmeli, Yehuda; Nutman, Amir; Levi, Inbar; Adler, Amos; Durante-Mangoni, Emanuele; Andini, Roberto; Cavezza, Giusi; Mouton, Johan W; Wijma, Rixt A; Theuretzbacher, Ursula; Friberg, Lena E; Kristoffersson, Anders N; Zusman, Oren; Koppel, Fidi; Dishon Benattar, Yael; Altunin, Sergey; Paul, Mical

    2016-01-01

    Introduction The emergence of antibiotic-resistant bacteria has driven renewed interest in older antibacterials, including colistin. Previous studies have shown that colistin is less effective and more toxic than modern antibiotics. In vitro synergy studies and clinical observational studies suggest a benefit of combining colistin with a carbapenem. A randomised controlled study is necessary for clarification. Methods and analysis This is a multicentre, investigator-initiated, open-label, randomised controlled superiority 1:1 study comparing colistin monotherapy with colistin–meropenem combination therapy for infections caused by carbapenem-resistant Gram-negative bacteria. The study is being conducted in 6 centres in 3 countries (Italy, Greece and Israel). We include patients with hospital-associated and ventilator-associated pneumonia, bloodstream infections and urosepsis. The primary outcome is treatment success at day 14, defined as survival, haemodynamic stability, stable or improved respiratory status for patients with pneumonia, microbiological cure for patients with bacteraemia and stability or improvement of the Sequential Organ Failure Assessment (SOFA) score. Secondary outcomes include 14-day and 28-day mortality as well as other clinical end points and safety outcomes. A sample size of 360 patients was calculated on the basis of an absolute improvement in clinical success of 15% with combination therapy. Outcomes will be assessed by intention to treat. Serum colistin samples are obtained from all patients to obtain population pharmacokinetic models. Microbiological sampling includes weekly surveillance samples with analysis of resistance mechanisms and synergy. An observational trial is evaluating patients who met eligibility requirements but were not randomised in order to assess generalisability of findings. Ethics and dissemination The study was approved by ethics committees at each centre and informed consent will be obtained for all patients. The

  15. Protocol for an open-label, single-arm trial of HIV pre-exposure prophylaxis (PrEP) among people at high risk of HIV infection: the NSW Demonstration Project PRELUDE

    Science.gov (United States)

    Vaccher, S; Grulich, A; McAllister, J; Templeton, D J; Bloch, M; McNulty, A; Holden, J; Poynten, I M; Prestage, G; Zablotska, I

    2016-01-01

    Introduction Despite a number of HIV prevention strategies, the number of new HIV infections remains high. In Australia, over three-quarters of new HIV diagnoses are in gay and bisexual men (GBM). Pre-exposure prophylaxis (PrEP) has been shown to be effective at preventing new HIV infections in several randomised trials. The PRELUDE study aims to evaluate the implementation of PrEP in healthcare settings in New South Wales (NSW), Australia, among a sample of high-risk adults. Methods and analysis PRELUDE is an ongoing open-label, single-arm demonstration project, conducted in public and private clinics across NSW, Australia. Enrolment began in November 2014. The study is designed for 300 high-risk participants—mainly GBM and heterosexual women. Participants receive daily oral PrEP, composed of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF), for up to 2.5 years. Quarterly study visits include testing for HIV and sexually transmitted infections (STIs), assessment of ongoing eligibility and side effects, and self-reported adherence. Following each study visit, online behavioural surveys are administered to collect information on medication adherence, risk behaviours and attitudes. Blood samples will be collected in a subset of patients 1, 6 and 12 months after PrEP initiation to measure FTC/TDF concentrations. Analyses using longitudinal regression models will focus on feasibility, adherence, safety, tolerability and effects of PrEP on behaviour. This study will inform PrEP policy and guide the implementation of PrEP in Australia in people at high risk of HIV. Ethics and dissemination The study will be conducted in accordance with the Declaration of Helsinki. All patients will provide written informed consent prior to participation in the study. Publications relating to each of the primary end points will be gradually released after 12 months of follow-up is complete. Trial registration number NCT02206555; Pre-results. PMID:27324719

  16. 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

  17. 24周综合运动对45至59岁中年人群膝关节等速肌力干预效果的研究%Intervention outcomes of 24-week comprehensive exercise on knee isokinetic muscle strength in 45-59-year-old middle-aged population

    Institute of Scientific and Technical Information of China (English)

    高雪峰; 徐勇灵; 张晓文; 陈守超

    2015-01-01

    目的 探讨24周综合运动干预方案对中年健身人群膝关节肌群力量素质的影响.方法 选取年龄45至49岁中年男性21人、女性34人进行运动干预并进行等速肌力测量膝关节肌群,指标包括屈膝峰值力矩(FPT)、伸膝峰值力矩(EPT)、屈膝相对峰值力矩(FPT/BW)、屈膝相对峰值力矩(EPT/BW)、屈伸力矩比(F/E)、屈膝总功(FTW)、伸膝总功(ETW)、屈膝平均功率(FAP)、伸膝平均功率(EAP).结果 男性受试者在60°/s速度运动干预16周、24周后较运动干预前FPT(屈)分别增加14.18%、11.52%,FPT/BW(屈)分别增加16.39%、15.57%,EPT/BW(伸)分别增加0.45%、6.28%,F/E、FTW(屈)、ETP(伸)等指标呈现出明显增加.在180°/s速度下上述各指标增加幅度更为明显.女性受试者在60°/s速度运动干预16周、24周后较运动干预前FPT(屈)分别增加29.48%、27.66%,FPT/BW(屈)分别增加29.76%、29.76%,在180./s速度下除EPT/BW(伸)、ETP(伸)无明显变化外,上述各指标呈现出更为显著的增加.结论 24周综合运动干预对中年健身人群膝关节肌群力量素质有明显改善,本方案对中年人群膝关节肌群的锻炼有显著促进作用.%Objective To investigate the effects of the intervention protocol of 24-week comprehensive exercise on knee isokinetic muscle strength in middle-aged population.Methods Twentyone males and 34 females aged 45-49 years were included in the study and underwent exercise intervention and isokinetic muscle strength measurement to determine indicators of the knee muscle group,which included flexion peak torque (FPT),extension peak torque (EPT),FPT/BW,EPT/BW,Flexor/Extensor (F/ E),flexion total work (FTW),extensor total work (ETW),flexion average power (FAP),and extensor average power (EAP).Results The FPT (flexor),FPT/BW (flexor) and EPT/ BW (flexor) in male subjects were increased 14.18% vs.11.52%,16.39% vs.15.57%,and 0.45% vs.6.28% after received 60

  18. Efeito do Hólmio YAG laser (Ho: YAG sobre o tendão patelar de ratos após 12 e 24 semanas de seguimento The effects of Holmium YAG laser (Ho:YAG on the patellar tendon of rats after 12 and 24 weeks of follow up

    Directory of Open Access Journals (Sweden)

    Waldo Lino Júnior

    2005-01-01

    , com neoformação vascular evidente. No grupo de 24 semanas as fibras de colágeno se apresentavam com disposição regular e paralela ao longo eixo do tendão.The authors have studied the effects of the Holmium: Yttrium Aluminum Grenade (Ho:YAG laser on tendon sizes (proximal and distal length and width and on the cellularity and arrangement of collagen fibers in 20 Wistar variety, male, white, adult rats (Rattus Novergicus. The animals have been divided in two groups, according to the follow-up time (12 and 24 weeks and pursuant to the for form of laser application (continuous or two-point. A Holmium laser (pulsed, solid state, 2.1 micron waves, 40 watts, OmniTip 30º tip apparatus was used. After the animals were sacrificed, the proximal and distal length and width of the operated size of such rats were compared to those of the non-operated size be means of non-parametric testing (considering p=0,05. The length in the operated size was significantly bigger for both follow-up groups, when compared to the length of the non-operated size, however there was no significant difference in such measures in function of the type of laser application. In the same manner, the width, both in the proximal and distal regions, was significantly bigger in the operated size in both follow-up groups, without showing any significant difference whatsoever in function of the type of application. When the measures in both follow-up groups were compared, distal length and width showed a trend to become bigger after 24 weeks, while width in the proximal region was significantly bigger in this group. As for the subjective microscopic evaluation, both in longitudinal and cross sections, it was possible to observe and increase in the number of fibroblasts, mainly in the 12-week group. The average fibroblast concentration in the tendon with 24-week follow-up was group deemed to be intermediate between the 12-week group and non-operated tendon. The conjunctive tissue was exuberant in the region

  19. Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial

    DEFF Research Database (Denmark)

    Sternberg, Cora N; Skoneczna, Iwona; Kerst, J Martijn;

    2015-01-01

    143 to deferred treatment), and followed up until the data cutoff of Aug 21, 2013. After a median follow-up of 7.0 years (IQR 5.2-8.7), 66 (47%) of 141 patients in the immediate treatment group had died compared with 82 (57%) of 143 in the deferred treatment group. No significant improvement in...

  20. Feasibility of a prospective, randomised, open-label, international multicentre, phase III, non-inferiority trial to assess the safety of active surveillance for low risk ductal carcinoma in situ - The LORD study

    NARCIS (Netherlands)

    Elshof, Lotte E.; Tryfonidis, Konstantinos; Slaets, Leen; van Leeuwen-Stok, A. Elise; Skinner, Victoria P.; Dif, Nicolas; Pijnappel, Ruud M.; Bijker, Nina; Rutgers, Emiel J. Th.; Wesseling, Jelle

    2015-01-01

    Background: The current debate on overdiagnosis and overtreatment of screen-detected ductal carcinoma in situ (DCIS) urges the need for prospective studies to address this issue. A substantial number of DCIS lesions will never form a health hazard, particularly if it concerns non-to slow-growing low

  1. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial

    NARCIS (Netherlands)

    Donker, M.; Tienhoven, G. van; Straver, M.E.; Meijnen, P.; Velde, C.J. van de; Mansel, R.E.; Cataliotti, L.; Westenberg, A.H.; Klinkenbijl, J.H.G.; Orzalesi, L.; Bouma, W.H.; Mijle, H.C. van der; Nieuwenhuijzen, G.A.; Veltkamp, S.C.; Slaets, L.; Duez, N.J.; Graaf, P.W. de; Dalen, T. van; Marinelli, A.; Rijna, H.; Snoj, M.; Bundred, N.J.; Merkus, J.W.M.J.; Belkacemi, Y.; Petignat, P.; Schinagl, D.A.X.; Coens, C.; Messina, C.G.; Bogaerts, J.; Rutgers, E.J.

    2014-01-01

    BACKGROUND: If treatment of the axilla is indicated in patients with breast cancer who have a positive sentinel node, axillary lymph node dissection is the present standard. Although axillary lymph node dissection provides excellent regional control, it is associated with harmful side-effects. We ai

  2. Safety and reactogenicity of the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTPa-IPV/Hib) vaccine in healthy Vietnamese toddlers: An open-label, phase III study.

    Science.gov (United States)

    Anh, Dang Duc; Van Der Meeren, Olivier; Karkada, Naveen; Assudani, Deepak; Yu, Ta-Wen; Han, Htay Htay

    2016-03-01

    The introduction of combination vaccines plays a significant role in increasing vaccine acceptance and widening vaccine coverage. Primary vaccination against diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenza type b (Hib) diseases has been implemented in Vietnam. In this study we evaluated the safety and reactogenicity of combined diphtheria-tetanus-pertussis-inactivated polio (DTPa-IPV)/Hib vaccine when administered as a booster dose in 300 healthy Vietnamese children <2 years of age (mean age: 15.8 months). During the 4-day follow-up period, pain (31.7%) and redness (27.3%) were the most frequent solicited local symptoms. Pain (2%) was also the most frequent grade 3 local symptom. One subject reported 2 serious adverse events that were not causally related to the study vaccine. DTPa-IPV/Hib conjugate vaccine was well tolerated as a booster dose in healthy Vietnamese children aged <2 years. PMID:26337197

  3. 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

  4. European Organization for Research and Treatment of Cancer (EORTC) open label phase II study on glufosfamide administered as a 60-minute infusion every 3 weeks in recurrent glioblastoma multiforme

    NARCIS (Netherlands)

    M.J. van den Bent (Martin); R. Stupp (Roger); D. Lacombe (Denis); J.P. Desir; T. Lesimple; C. Dittrich (Christian); B. Baron; P. Fumoleau (Pierre); M.J.A. de Jonge (Maja); A. Brandes (Alba); J. Oliveira; M. Frenay (Marc); P. Chollet; M. Schuessler; A.F. Carpentier; W. Grisold (Wolfgang); D. Frappaz

    2003-01-01

    textabstractBACKGROUND: Glufosfamide is a new alkylating agent in which the active metabolite of isophosphoramide mustard is covalently linked to beta-D-glucose to target the glucose transporter system and increase intracellular uptake in tumor cells. We investigated this drug in a

  5. Health-related quality of life in patients with high-risk low-grade glioma (EORTC 22033-26033) : a randomised, open-label, phase 3 intergroup study

    NARCIS (Netherlands)

    Reijneveld, Jaap C; Taphoorn, Martin J B; Coens, Corneel; Bromberg, Jacoline E C; Mason, Warren P; Hoang-Xuan, Khê; Ryan, Gail; Hassel, Mohamed Ben; Enting, Roelien H; Brandes, Alba A; Wick, Antje; Chinot, Olivier; Reni, Michele; Kantor, Guy; Thiessen, Brian; Klein, Martin; Verger, Eugenie; Borchers, Christian; Hau, Peter; Back, Michael; Smits, Anja; Golfinopoulos, Vassilis; Gorlia, Thierry; Bottomley, Andrew; Stupp, Roger; Baumert, Brigitta G

    2016-01-01

    BACKGROUND: Temozolomide chemotherapy versus radiotherapy in patients with a high-risk low-grade glioma has been shown to have no significant effect on progression-free survival. If these treatments have a different effect on health-related quality of life (HRQOL), it might affect the choice of ther

  6. An open-label Phase I/II clinical trial of pyrimethamine for the treatment of patients affected with chronic GM2 gangliosidosis (Tay-Sachs or Sandhoff variants).

    Science.gov (United States)

    Clarke, Joe T R; Mahuran, Don J; Sathe, Swati; Kolodny, Edwin H; Rigat, Brigitte A; Raiman, Julian A; Tropak, Michael B

    2011-01-01

    Late-onset GM2 gangliosidosis is an autosomal recessive, neurodegenerative, lysosomal storage disease, caused by deficiency of ß-hexosaminidase A (Hex A), resulting from mutations in the HEXA (Tay-Sachs variant) or the HEXB (Sandhoff variant) genes. The enzyme deficiency in many patients with juvenile or adult onset forms of the disease results from the production of an unstable protein, which becomes targeted for premature degradation by the quality control system of the smooth endoplasmic reticulum and is not transported to lysosomes. In vitro studies have shown that many mutations in either the α or β subunit of Hex A can be partially rescued, i.e. enhanced levels of both enzyme protein and activity in lysosomes, following the growth of patient cells in the presence of the drug, pyrimethamine. The objectives of the present clinical trial were to establish the tolerability and efficacy of the treatment of late-onset GM2 gangliosidosis patients with escalating doses of pyrimethamine, to a maximum of 100 mg per day, administered orally in a single daily dose, over a 16-week period . The primary objective, tolerability, was assessed by regular clinical examinations, along with a panel of hematologic and biochemical studies. Although clinical efficacy could not be assessed in this short trial, treatment efficacy was evaluated by repeated measurements of leukocyte Hex A activity, expressed relative to the activity of lysosomal ß-glucuronidase. A total of 11 patients were enrolled, 8 males and 3 females, aged 23 to 50 years. One subject failed the initial screen, another was omitted from analysis because of the large number of protocol violations, and a third was withdrawn very early as a result of adverse events which were not drug-related. For the remaining 8 subjects, up to a 4-fold enhancement of Hex A activity at doses of 50 mg per day or less was observed. Additionally marked individual variations in the pharmacokinetics of the drug among the patients were noted. However, the study also found that significant side effects were experienced by most patients at or above 75 mg pyrimethamine per day. We concluded that pyrimethamine treatment enhances leukocyte Hex A activity in patients with late-onset GM2 gangliosidosis at doses lower than those associated with unacceptable side effects. Further plans are underway to extend these trials and to develop methods to assess clinical efficacy. PMID:20926324

  7. Phase II, Open Label, Randomized Comparative Trial of Ondansetron Alone versus the Combination of Ondansetron and Aprepitant for the Prevention of Nausea and Vomiting in Patients with Hematologic Malignancies Receiving Regimens Containing High-Dose Cytarabine

    Directory of Open Access Journals (Sweden)

    Talha Badar

    2015-01-01

    Full Text Available Background. Aprepitant is a P/neurokinin-1 receptor antagonist approved for the prevention of CINV in moderate emetic risk chemotherapy. We explored its effectiveness in patients with leukemia receiving cytarabine-based chemotherapy. Methods. Patients were randomized to ondansetron (OND 8 mg IV 30 minutes before cytarabine followed by 24 mg IV continuous infusion daily until 6–12 hours after the last dose of chemotherapy alone or with aprepitant (APREP oral 125 mg 6–12 hrs before chemotherapy and 80 mg daily until 1 day after the last dose of chemotherapy. Results. Forty-nine patients were enrolled in each arm; 42 in OND and 41 in OND + APREP arm were evaluable for efficacy. The ORR with OND + APREP was 80% compared to 67% with OND alone (P=0.11. On days 6 and 7, higher proportion of patients treated with OND + APREP were free from nausea (74%, 74% versus 68%, 67%; P=0.27 and 0.18, resp.. Requirement of rescue medications on days 2 and 3 was fewer in OND + APREP arm 7% and 5% compared to 21% and 16% in the OND arm, respectively (P=0.06 and P=0.07. Conclusions. There was a trend for overall improvement in emesis with ondansetron plus aprepitant. The potential benefit of this approach with specific chemotherapy combinations remains to be determined.

  8. Single and Multiple Dose Pharmacokinetics, Pharmacodynamics and Safety of the Novel Lipoprotein-Associated Phospholipase A2 Enzyme Inhibitor Darapladib in Healthy Chinese Subjects: An Open Label Phase-1 Clinical Trial.

    Directory of Open Access Journals (Sweden)

    Chaoying Hu

    Full Text Available Darapladib is a lipoprotein-associated phospholipase A2 (Lp-PLA2 inhibitor. This study evaluated the pharmacokinetics, pharmacodynamics and safety of darapladib in healthy Chinese subjects.Twenty-four subjects received darapladib 160 mg orally, approximately 1 hour after a standard breakfast, as a single dose and once daily for 28 days. Non-compartmental methods were used to determine the single and multiple dose pharmacokinetics of darapladib and its metabolite SB-553253. Repeat dose Lp-PLA2 activity and safety were evaluated.Systemic exposure (AUC(0-T, Cmax geometric mean (CVb% of darapladib was higher after multiple-dosing (519 ng.h/mL (33.3%, 34.4 ng/mL (49.9% compared to single-dose administration (153 ng.h/mL (69.0%, 17.9 ng/mL (55.2%. The steady-state accumulation ratio was less than unity (Rs = 0.80, indicating time-dependent pharmacokinetics of darapladib. Darapladib steady-state was reached by Day 14 of once daily dosing. Systemic exposure to SB-553253 was lower than darapladib with median (SB-553253: darapladib ratios for AUC(0-τ of 0.0786 for single dose and 0.0532 for multiple dose administration. On Day 28, pre-dose and maximum inhibition of Lp-PLA2 activity was approximately 70% and 75% relative to the baseline value, respectively and was dependent of darapladib concentration. The most common adverse events (≥ 21% subjects were abnormal faeces, abnormal urine odour, diarrhoea and nasopharyngitis.Darapladib 160 mg single and repeat doses were profiled in healthy Chinese subjects. Single dose systemic exposure to darapladib in healthy Chinese subjects was consistent with that observed previously in Western subjects whereas steady-state systemic exposure was approximately 65% higher in Chinese than Western subjects. The Lp-PLA2 activity and adverse event profile were similar in healthy Chinese and previous reports in Western subjects. Ethnic-specific dose adjustment of darapladib is not considered necessary for the Chinese population.ClinicalTrials.gov NCT02000804.

  9. Efficacy and safety profile of combination of tramadol-diclofenac versus tramadol-paracetamol in patients with acute musculoskeletal conditions, postoperative pain, and acute flare of osteoarthritis and rheumatoid arthritis: a Phase III, 5-day open-label study

    Science.gov (United States)

    Chandanwale, Ajay S; Sundar, Subramanian; Latchoumibady, Kaliaperumal; Biswas, Swati; Gabhane, Mukesh; Naik, Manoj; Patel, Kamlesh

    2014-01-01

    Objective We aimed to evaluate the safety and efficacy of a fixed-dose combination (FDC) of tramadol and diclofenac versus a standard approved FDC of tramadol and paracetamol, in patients with acute moderate to severe pain. Methods A total of 204 patients with moderate to severe pain due to acute musculoskeletal conditions (n=52), acute flare of osteoarthritis (n=52), acute flare of rheumatoid arthritis (n=50), or postoperative pain (n=50) were enrolled in the study at baseline. Each disease category was then randomized to receive either of two treatments for 5 days: group A received an FDC of immediate-release tramadol hydrochloride (50 mg) and sustained-release diclofenac sodium (75 mg) (one tablet, twice daily), and group B received an FDC of tramadol hydrochloride (37.5 mg) and paracetamol (325 mg) (two tablets every 4–6 hours, up to a maximum of eight tablets daily). The primary efficacy end points were reductions in pain intensity from baseline at day 3 and day 5 as assessed by a Visual Analog Scale (VAS) score. Results Group A showed a significant reduction in the VAS score for overall pain from baseline on day 3 (P=0.001) and day 5 (P<0.0001) as compared with group B. The combination of tramadol-diclofenac resulted in few mild to moderate adverse events (nausea, vomiting, epigastric pain, and gastritis), which required minimal management, without any treatment discontinuation. The number of adverse events in group A was nine (8.82%) compared with 22 (21.78%) in group B, after 5 days of treatment. Conclusion An FDC of tramadol-diclofenac showed a significantly greater reduction in pain intensity and was well tolerated compared with tramadol-paracetamol, resulting in better analgesia in patients suffering from moderate to severe pain due to acute musculoskeletal conditions, postoperative pain following orthopedic surgery, or acute flare of osteoarthritis and rheumatoid arthritis. PMID:25152629

  10. Efficacy and safety analysis of trastuzumab and paclitaxel based regimen plus carboplatin or epirubicin as neoadjuvant therapy for clinical stage II-III, HER2-positive breast cancer patients: a phase 2, open-label, multicenter, randomized trial.

    Science.gov (United States)

    Huang, Liang; Chen, Sheng; Yang, Wentao; Xu, Binghe; Huang, Tao; Yang, Hongjian; Zheng, Hong; Wang, Yongsheng; Song, Erwei; Zhang, Jin; Cui, Shude; Pang, Da; Tang, Lili; Lei, Yutao; Geng, Cuizhi; Shao, Zhiming

    2015-07-30

    This trial was designed to compare the efficacy and safety between epirubicin (E) and carboplatin (C) in combination with paclitaxel (P) and trastuzumab (H) in neoadjuvant setting. In 13 Chinese cancer centers, 100 patients with HER2-positive, locally advanced breast cancer were 1:1 randomized to receive medication as follows: trastuzumab and paclitaxel weekly combined with carboplatin weekly for PCH group, or epirubicin every 3 weeks for PEH group. Patients were given 4 to 6 cycles of chemotherapy. The primary endpoint was pathologic complete response (pCR) rate, which was no significant difference in PCH and PEH regimen (39.1% vs. 48.8%; p=0.365). However, PEH regimen achieved higher pCR in luminal-B (HER2-poitive) subgroup (55.0% vs. 24.0%; p = 0.033), but not in ERBB2+ subgroup (42.9% vs. 57.1%; p = 0.355). PEH regimen showed a favorable efficacy in PIK3CA mutated subgroup (69.2% vs.23.5%, p=0.012). No significant difference was observed in the subgroup analysis of TP53 mutation status, PTEN expression, FCGR2A SNP and FCGR3A SNP. Both regimens as neoadjuvant chemotherapy achieve similar efficacy and safety. PEH might improve pCR rate, especially in the luminal-B subtype and PIK3CA mutation subtype. PEH is feasible and less likely to increase the incidence of acute cardiac events compared to PCH. PMID:26084292

  11. An adjuvant autologous therapeutic vaccine (HSPPC-96; vitespen) versus observation alone for patients at high risk of recurrence after nephrectomy for renal cell carcinoma: a multicentre, open-label, randomised phase III trial.

    NARCIS (Netherlands)

    Wood, C.; Srivastava, P.; Bukowski, R.; Lacombe, L.; Gorelov, A.I.; Gorelov, S.; Mulders, P.F.A.; Zielinski, H.; Hoos, A.; Teofilovici, F.; Isakov, L.; Flanigan, R.; Figlin, R.; Gupta, R.; Escudier, B.

    2008-01-01

    BACKGROUND: Treatment of localised renal cell carcinoma consists of partial or radical nephrectomy. A substantial proportion of patients are at risk for recurrence because no effective adjuvant therapy exists. We investigated the use of an autologous, tumour-derived heat-shock protein (glycoprotein

  12. Safety and reactogenicity of the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTPa-IPV/Hib) vaccine in healthy Vietnamese toddlers: An open-label, phase III study.

    Science.gov (United States)

    Anh, Dang Duc; Van Der Meeren, Olivier; Karkada, Naveen; Assudani, Deepak; Yu, Ta-Wen; Han, Htay Htay

    2016-03-01

    The introduction of combination vaccines plays a significant role in increasing vaccine acceptance and widening vaccine coverage. Primary vaccination against diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenza type b (Hib) diseases has been implemented in Vietnam. In this study we evaluated the safety and reactogenicity of combined diphtheria-tetanus-pertussis-inactivated polio (DTPa-IPV)/Hib vaccine when administered as a booster dose in 300 healthy Vietnamese children <2 years of age (mean age: 15.8 months). During the 4-day follow-up period, pain (31.7%) and redness (27.3%) were the most frequent solicited local symptoms. Pain (2%) was also the most frequent grade 3 local symptom. One subject reported 2 serious adverse events that were not causally related to the study vaccine. DTPa-IPV/Hib conjugate vaccine was well tolerated as a booster dose in healthy Vietnamese children aged <2 years.

  13. 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

  14. A 2-way cross-over, open-labeled trial to compare efficacy and safety of insulin Aspart and Novolin R delivered with CSII in 21 Chinese diabetic patients

    Institute of Scientific and Technical Information of China (English)

    BI Yu-fang; NING Guang; ZHAO Lie-bin; LI Xiao-ying; WANG Wei-qing; SUN Shou-yue; CHEN Yu-hong; HONG Jie; SU Ting-wei; LIU Jian-min

    2007-01-01

    Background Subcutaneous absorption is accelerated by the monomeric conformation of insulin Aspart, which provides good glycemic control with a lower risk of hypoglycemia and less body weight increase. In the present study we investigated the efficacy and safety of a rapid-acting human insulin analogue (insulin Aspart) delivered with continuous subcutaneous insulin infusion (CSII) into Chinese diabetic patients.Methods Atotal of 21 patients with type 1 or type 2 diabetes were recruited for the 2-way cross-over, open-labeled trial,and then randomized to Group A (n=10, treated with insulin Aspart) or Group B (n=11, treated with Novolin R). Insulin Aspart and Novolin R were administered by CSII. Capillary glucose concentrations were measured at 8 time points,pre-prandial and postprandial, bedtime (10 pm), midnight (2 am) every day during the treatment.Results The average capillary glucose profiles for the day were much better controlled in Group A than in Group B (P<0.01). The blood glucose levels were particularly better controlled in Group A than in Group B at pre-breakfast ((6.72±1.24) mmol/L vs (7.84±1.58) mmol/L, P=0.014), post-breakfast ((8.96±2.41) mmol/L vs (11.70±3.11) mmol/L,P=0.0028), post-supper ((8.15±2.10) mmol/L vs (10.07±2.36) mmol/L, P=0.008), bed time ((7.73±1.72) mmol/L vs (9.39±2.05) mmol/L, P=0.007) and midnight ((6.32±1.16) mmol/L vs (7.48±1.36) mmol/L, P=0.0049). There was no significant difference in the frequency of hypoglycemic episodes between the two groups.Conclusion Insulin Aspart results in better control of blood glucose levels than regular human insulin (Novolin R) in diabetic patients during delivery by CSII.

  15. Recent availability of two novel, fixed formulations of antiretroviral nucleoside analogues: a 12-month prospective, open-label survey of their practical use and therapeutic perspectives in antiretroviral-naive and -experienced patients.

    Science.gov (United States)

    Manfredi, Roberto; Calza, Leonardo

    2008-04-01

    The recent introduction of novel, fixed nucleoside-nucleotide reverse transcriptase inhibitor (NRTI) combinations (tenofovir-emtricitabine, and abacavir-lamivudine) expanded the spectrum of available formulations and concurrently increased patients' adherence levels. A prospective survey of the open-label use of these two fixed combinations was performed in 158 patients belonging to our single-center cohort of more than 1,000 HIV-infected subjects enrolled in the last 18 months, and followed for at least 12 months. During the last 18 months, 95 consecutive, evaluable patients (60.1%) received for the first time tenofovir-emtricitabine, or abacavir-lamivudine (63 patients, 39.9%), and were followed for at least 12 months with periodic clinical and laboratory examinations. Among the 53 evaluable patients who were naïve to all antiretrovirals, tenofovir-emtricitabine has been given to 42 subjects (79.2%), mostly associated with efavirenz (26 cases), or different boosted protease inhibitors (16 subjects), whereas abacavir-lamivudine was administered to 11 patients (in 10 cases of 11, together with boosted protease inhibitors). In the remaining 105 patients, tenofovir-emtricitabine or abacavir-lamivudine therapy represented a switch from a prior combination antiretroviral regimen, and was predominantly associated with boosted protease inhibitors (61 patients), versus efavirenz or nevirapine (26 cases), or other drug combinations containing protease inhibitors (the remaining 18 patients). Among the 105 pretreated patients, the prescription of tenofovir-emtricitabine (53 patients) was as frequent as that of abacavir-lamivudine (52 cases), and the therapeutic change was primarily prompted by toxicity or poor tolerability (59 patients), followed by therapeutic failure and viral resistance (46 cases as a whole), and always encompassed a regimen simplification also. Both fixed combinations were well tolerated, and an adherence rate more than 90% was estimated among evaluable

  16. PHARMACOKINETIC AND BIOEQUIVALENCE COMPARISON BETWEEN EXTENDED RELEASE CAPSULES OF VENLAFAXINE HYDROCHLORIDE 150MG: AN OPEN LABEL, BALANCED, RANDOMIZED-SEQUENCE, SINGLE-DOSE, TWO-PERIOD CROSSOVER STUDY IN HEALTHY INDIAN MALE VOLUNTEERS

    Directory of Open Access Journals (Sweden)

    I.Sarath chandiran

    2011-03-01

    Full Text Available This bioequivalence study was designed to determine the pharmacokinetic, bioavailability and bioequivalence of Venlafaxine HCl 150 mg Extended Release Capsules in comparison with Effexor®-XR 150mg Extended Release Capsules after single dose administration under fed conditions in 20 healthy adult male subjects. Therefore the design of an open label, balanced, randomized, two-sequence, single dose, two way crossover study with a washout period of at least 7 days was used.Each volunteer received a 150 mg capsule of the reference or test drug respectively. On the day of dosing, blood samples were collected before dosing and at various time points up to 72 hours after dosing. Analysis of venlafaxine and its metabolite O-Desmethylvenlafaxine concentrations was performed using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS method. The pharmacokinetic parameters including Cmax, AUC0-t, AUC0-inf, Tmax, t1/2 and Kel were analyzed using the non-compartmental model. Drug safety and tolerability were assessed.The pharmacokinetic parameters including Cmax, AUC0-t, AUC0-inf, Tmax, t1/2 and Kel were analyzed using the non-compartmental model. Drug safety and tolerability were assessed. The primary pharmacokinetic parameters (Cmax, AUC0-t and AUC0-inf 90%CI were within the 80 to 125% interval required for bioequivalence as stipulated in the current regulations of the USFDA acceptance criteria. The geometric mean ratios (Test/Reference between the two products of extended-release venlafaxine capsule under fed condition were 104.91% (92.86%-118.53% and 114.41% (103.43%-124.55% for Cmax ratios, 102.24% (95.95%-108.94% and 105.27% (96.76%-114.53% for AUC0-t ratios and 101.66% (95.73%-107.97% and 104.71% (96.13%-114.05% for AUC0-inf ratios of Venlafaxine and its metabolite O-Desmethylvenlafaxine (ODV respectively. 20 volunteers had completed both treatment periods. There was no significant difference of the Tmax parameter between the two

  17. Comparisons of the pharmacokinetics and tolerability of fixed-dose combinations of amlodipine besylate/losartan and amlodipine camsylate/losartan in healthy subjects: a randomized, open-label, single-dose, two-period, two-sequence crossover study

    Science.gov (United States)

    Choi, YoonJung; Lee, SeungHwan; Cho, Sang-Min; Kang, Won-Ho; Nam, Kyu-Yeol; Jang, In-Jin; Yu, Kyung-Sang

    2016-01-01

    Background A fixed-dose combination (FDC) of amlodipine and losartan has been used to reduce blood pressure in patients whose hypertension is not sufficiently controlled with either drug alone. The aim of this study was to evaluate the pharmacokinetic (PK) characteristics and tolerability of an FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine)/50 mg losartan potassium compared to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium in healthy subjects. Subjects and methods A randomized, open-label, single-dose, two-period, two-sequence crossover study was conducted on 46 healthy male subjects. Blood concentrations were measured by liquid chromatography–tandem mass spectrometry. Blood samples were collected up to 144 hours post dose for each period. PK parameters were calculated in each treatment group using a noncompartmental method. The 90% confidence intervals (CIs) of the geometric mean ratios of the two treatments for the maximum plasma concentration (Cmax) and the area under the concentration curve from time zero to the last quantifiable time point (AUC0–t) were estimated. Tolerability assessments were performed for all subjects who received the drug at least once. Results The PK profiles of the two treatments were similar. For amlodipine, the geometric mean ratios (90% CIs) of amlodipine besylate to amlodipine camsylate for the Cmax and AUC0–t were 0.98 (0.94−1.01) and 0.97 (0.93−1.01), respectively. The corresponding values for losartan were 0.91 (0.81−1.02) and 1.05 (0.98−1.12), respectively. The incidence of adverse events was not significantly different between the two treatments, and both were well tolerated. Conclusion An FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine)/50 mg losartan potassium produced similar results to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium treatment with respect to the PK parameters of amlodipine and losartan based on Cmax and AUC0–t values. The amlodipine besylate

  18. SmartPill® as an objective parameter for determination of severity and duration of postoperative ileus: study protocol of a prospective, two-arm, open-label trial (the PIDuSA study)

    Science.gov (United States)

    Vilz, Tim O; Pantelis, Dimitrios; Lingohr, Philipp; Fimmers, Rolf; Esmann, Anke; Randau, Thomas; Kalff, Jörg C; Coenen, Martin; Wehner, Sven

    2016-01-01

    Introduction Postoperative ileus (POI) is a frequent complication after abdominal surgery (AS). Until today, neither a prophylaxis nor an evidence-based therapy exists. This originates from the absence of objective parameters evaluating the severity and duration of POI resulting in clinical trials of modest quality. The SmartPill®, a capsule which frequently measures pH value, temperature and intraluminal pressure after swallowing, offers an elegant option for analysing gastrointestinal (GI) transit times and smooth muscle activity in vivo. As the use in patients in the first months after AS is not covered by the marketing authorisation, we aim to investigate the safety and feasibility of the SmartPill® immediately after surgery. Additionally, we analyse the influence of prokinetics and laxatives as well as standardised physiotherapy on postoperative bowel contractility, as scientific evidence of its effects is still lacking. Methods and analysis The PIDuSA study is a prospective, single-centre, two-arm, open-label trial. The SmartPill® will be applied to 55 patients undergoing AS having a high risk for POI and 10 patients undergoing extra-abdominal surgery rarely developing POI. The primary objective is the safety of the SmartPill® in patients after surgery on the basis of adverse device effects/serious adverse device effects (ADE/SADE). The sample size suggests that events with a probability of 3% could be seen with a certainty of 80% for at least once in the sample. Secondary objective is the analysis of postoperative intestinal activity in the GI tract in both groups. Furthermore, clinical signs of bowel motility disorders will be correlated to the data measured by the SmartPill® to evaluate its significance as an objective parameter for assessing POI severity. Additionally, effects of prokinetics, laxatives and physiotherapy on postoperative peristaltic activity recorded by the SmartPill® will be analysed. Ethics and dissemination The protocol was

  19. Repeated treatment of recurrent uncomplicated Plasmodium falciparum malaria in Senegal with fixed-dose artesunate plus amodiaquine versus fixed-dose artemether plus lumefantrine: a randomized, open-label trial

    Directory of Open Access Journals (Sweden)

    Barry Aichatou

    2011-08-01

    Full Text Available Abstract Background The use of artemisinin-based combination therapy (ACT is currently recommended for treating uncomplicated malaria. The objective was to assess the efficacy and safety of repeated administrations of two fixed-dose presentations of ACT - artesunate plus amodiaquine (ASAQ and artemether-lumefantrine (AL - in subsequent episodes of Plasmodium falciparum malaria. Methods A randomized comparative study was conducted in a rural community of central Senegal from August 2007 to January 2009. Children and adults with uncomplicated P. falciparum malaria were randomized to receive open-label ASAQ once daily or AL twice daily for three days. Drug doses were given according to body weight. Treatments for first episodes were supervised. For subsequent episodes, only the first intake of study drug was supervised. ECGs and audiograms were performed in patients ≥12 years of age. Primary outcome was adequate clinical and parasitological response rate (ACPR after polymerase chain reaction (PCR correction on day 28 for the first episode. Results A total of 366 patients were enrolled in the two groups (ASAQ 184, AL 182 and followed up during two malaria transmission seasons. In the intent-to-treat population, PCR-corrected ACPRs at day 28 for the first episode were 98.4% and 96.2%, respectively, in the ASAQ and AL groups. For the per-protocol population (ASAQ 183, AL 182, PCR-corrected ACPRs at day 28 for the first episode were 98.9% and 96.7%, respectively. A 100% ACPR rate was obtained at day 28 in the 60 and four patients, respectively, who experienced second and third episodes. Treatment-related adverse events were reported in 11.7% of the patients, without significant differences between the two groups. A better improvement of haemoglobin at day 28 was noted in the ASAQ versus the AL group (12.2 versus 11.8 g/dL; p = 0.03. No sign of ototoxicity was demonstrated. A prolongation of the QTc interval was observed in both groups during

  20. Efficacy of intravenous hydrocortisone administered 2-4 h prior to antivenom as prophylaxis against adverse drug reactions to snake antivenom in Sri Lanka: An open labelled randomized controlled trial.

    Science.gov (United States)

    Kularatne, Senanayake A M; Weerakoon, Kosala; Silva, Anjana; Maduwage, Kalana; Walathara, Chamara; Rathnayake, Ishani; Medagedara, Senal; Paranagama, Ranjith; Mendis, Suresh; Kumarasiri, P V R

    2016-09-15

    The prevention of adverse drug reactions to antivenom serum poses a formidable challenge in the management of snakebite. Hydrocortisone is being used concurrently with antivenom in order to prevent these adverse drug reactions without a proven benefit. However, all previous studies seemed to ignore the testing of effectiveness of hydrocortisone therapy during its pharmacological effects, which come hours later. On this principle, we aimed to test the effectiveness of intravenous hydrocortisone given 2 h or more prior to the commencement of antivenom therapy to reduce adverse drug reactions to antivenom. In an open-labelled randomized controlled trial, patients with a history of snakebite were randomly assigned to receive either 500 mg intravenous hydrocortisone bolus given 2 h or more prior to antivenom therapy (Group A) or at the time of antivenom therapy (Group B). The primary endpoint was the reduction of adverse drug reactions to antivenom of any grade of severity within the first 48 h. This trial has been registered with the "Sri Lanka Clinical Trials Registry", number SLCTR/2010/005. A total of 236 patients were randomized to group A or Group B. In the group A, 38 participants received hydrocortisone 2 h before administration of antivenom whilst 33 received hydrocortisone less than 2 h before administration of antivenom. In the Group B, 84 participants received hydrocortisone at the time of antivenom therapy. In Group A (n, 38), and Group B (n, 84), 15 patients (39%) and 29 patients (35%) developed reactions respectively and the difference is not significant (p = 0.598). Moreover, hydrocortisone therapy did not significantly reduce the occurrence of antievnom reactions of any grade of severity. Further, it didn't delay the occurrence of antivenom reactions in patients who received hydrocortisone either more than 2 h or less than 2 h before the antivenom as opposed to the control group (group B). Intravenous hydrocortisone shows no difference in the

  1. An Open-label, Self-control, Prospective Study on Cognitive Function, Academic Performance, and Tolerability of Osmotic-release Oral System Methylphenidate in Children with Attention-deficit Hyperactivity Disorder

    Institute of Scientific and Technical Information of China (English)

    Yi Zheng; Jian-Min Liang; Hong-Yun Gao; Zhi-Wei Yang; Fu-Jun Jia; Yue-Zhu Liang; Fang Fang

    2015-01-01

    Background: Attention-deficit hyperactivity disorder (ADHD) is the most common mental and behavioral disorder in school-aged children.This study evaluated the effect of osmotic-release oral system (OROS) methylphenidate (MPH) on cognitive function and academic performance of Chinese school-aged children with ADHD.Methods: This 12-week, prospective, multicenter, open-label, self-controlled study enrolled 153 Chinese school-aged children with ADHD and 41 non-ADHD children.Children with ADHD were treated with once-daily OROS-MPH (18 mg, 36 mg, or 54 mg).The primary endpoints were Inattention/Overactivity (I/O) with Aggression Conners Behavior Rating Scale (IOWA) and Digit Span Test at week 12 compared with baseline.Secondary endpoints included opposition/defiant (O/D) subscale of IOWA, Clinical Global Impression (CGI), Coding Test, Stroop Color-word Test, Wisconsin Card Sorting Test (WCST), academic performance on teacher-rated school examinations,and safety at week 12 compared with baseline.Both non-ADHD and ADHD children received the same frequency of cognitive operational test to avoid the possible bias caused by training.Results: A total of 128 patients were evaluated with cognitive assessments.The OROS-MPH treatment significantly improved IOWA Conners I/O subscale scores at week 12 (3.8 ± 2.3) versus baseline (10.0 ± 2.4;P < 0.0001).Digit Span Test scores improved significantly (P < 0.0001) with a high remission rate (81.1%) at week 12 versus baseline.A significant (P < 0.0001) improvement was observed in O/D subscale of IOWA, CGI, Coding Test, Stroop Color-word Test, WCST, and academic performance at week 12 versus baseline.Very few practice-related improvements were noticed in the non-ADHD group at week 12 compared with baseline.No serious adverse events and deaths were reported during the study.Conclusions: The OROS-MPH treatment effectively controlled symptoms of ADHD and significantly improved academic performance and cognitive function of Chinese

  2. 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

    2008-09-01

    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

  3. Overall survival and final efficacy and safety results from a Japanese phase II study of axitinib in cytokine-refractory metastatic renal cell carcinoma

    OpenAIRE

    Eto, Masatoshi; Uemura, Hirotsugu; Tomita, Yoshihiko; Kanayama, Hiroomi; Shinohara, Nobuo; Kamei, Yoichi; Fujii, Yosuke; Umeyama, Yoshiko; Ozono, Seiichiro; Naito, Seiji; Akaza, Hideyuki; ,

    2014-01-01

    In an open-label, multicenter phase II study of Japanese patients with cytokine-refractory metastatic renal cell carcinoma, axitinib showed substantial antitumor activity with an acceptable safety profile. Here, we report overall survival and updated efficacy and safety results. Sixty-four Japanese patients with metastatic renal cell carcinoma following prior therapy with cytokines were treated with axitinib at a starting dose of 5 mg b.i.d. Following median treatment duration of 14.2 months,...

  4. Comparisons of the pharmacokinetics and tolerability of fixed-dose combinations of amlodipine besylate/losartan and amlodipine camsylate/losartan in healthy subjects: a randomized, open-label, single-dose, two-period, two-sequence crossover study

    Directory of Open Access Journals (Sweden)

    Choi Y

    2016-09-01

    Full Text Available YoonJung Choi,1 SeungHwan Lee,2 Sang-Min Cho,3 Won-Ho Kang,3 Kyu-Yeol Nam,4 In-Jin Jang,1 Kyung-Sang Yu1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine, 2Clinical Trials Center, Seoul National University Hospital, 3Research Institute, 4Global R&D, Korea United Pharm Inc., Seoul, Republic of Korea Background: A fixed-dose combination (FDC of amlodipine and losartan has been used to reduce blood pressure in patients whose hypertension is not sufficiently controlled with either drug alone. The aim of this study was to evaluate the pharmacokinetic (PK characteristics and tolerability of an FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine/50 mg losartan potassium compared to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium in healthy subjects. Subjects and methods: A randomized, open-label, single-dose, two-period, two-sequence crossover study was conducted on 46 healthy male subjects. Blood concentrations were measured by liquid chromatography–tandem mass spectrometry. Blood samples were collected up to 144 hours post dose for each period. PK parameters were calculated in each treatment group using a noncompartmental method. The 90% confidence intervals (CIs of the geometric mean ratios of the two treatments for the maximum plasma concentration (Cmax and the area under the concentration curve from time zero to the last quantifiable time point (AUC0–t were estimated. Tolerability assessments were performed for all subjects who received the drug at least once. Results: The PK profiles of the two treatments were similar. For amlodipine, the geometric mean ratios (90% CIs of amlodipine besylate to amlodipine camsylate for the Cmax and AUC0–t were 0.98 (0.94-1.01 and 0.97 (0.93-1.01, respectively. The corresponding values for losartan were 0.91 (0.81-1.02 and 1.05 (0.98-1.12, respectively. The incidence of adverse events was not significantly different between the two

  5. 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

  6. A phase I dose-escalation and pharmacokinetic study of enzastaurin and erlotinib in patients with advanced solid tumors

    OpenAIRE

    Padda, Sukhmani K.; Krupitskaya, Yelena; Chhatwani, Laveena; Fisher, George A; Colevas, Alexander D.; San Pedro-Salcedo, Melanie; Decker, Rodney; Latz, Jane E.; Wakelee, Heather A.

    2011-01-01

    Purpose Enzastaurin, an oral serine/threonine kinase inhibitor, targets the protein kinase C and AKT pathways with anti-tumor and anti-angiogenic effects. Erlotinib, an oral epidermal growth factor receptor (EGFR) inhibitor, has activity in solid tumors. Based on the promising combination of EGFR inhibitors and anti-angiogenic agents, this phase I trial was initiated. Methods This single-institution, open-label, non-randomized trial used a standard 3 + 3 dose-escalation model in patients with...

  7. Deferasirox in patients with iron overload secondary to hereditary hemochromatosis: results of a 1-yr Phase 2 study.

    Science.gov (United States)

    Cançado, Rodolfo; Melo, Murilo R; de Moraes Bastos, Roberto; Santos, Paulo C J L; Guerra-Shinohara, Elivira M; Chiattone, Carlos; Ballas, Samir K

    2015-12-01

    This open-label, prospective, phase 2 study evaluated the safety and efficacy of deferasirox (10 ± 5 mg/kg/d) in patients with hereditary hemochromatosis (HH) and iron overload refractory to or intolerant of phlebotomy. Ten patients were enrolled and all completed the 12-month treatment period. There were significant decreases from baseline to end of study (i.e., 12 months) in median serum ferritin (P hemochromatosis and could be a safe alternative to phlebotomy in selected patients.

  8. A phase II and pharmacodynamic study of sunitinib in relapsed/refractory oesophageal and gastro-oesophageal cancers

    OpenAIRE

    Wu, C.; S. Mikhail; Wei, L; Timmers, C; Tahiri, S.; Neal, A.; Walker, J; El-Dika, S; Blazer, M; Rock, J.; Clark, D J; X. Yang; Chen, J L; Liu, J.; Knopp, M.V.

    2015-01-01

    Background: Blockade of the vascular endothelial growth factor (VEGF) pathway shows evidence of activity in gastro-oesophageal (GE) and oesophageal cancer. We investigated the efficacy of sunitinib, a multikinase VEGF inhibitor, in patients with relapsed/refractory GE/oesophageal cancer. Methods: This was a single-stage Fleming phase II study. The primary end point was progression-free survival (PFS) at 24 weeks. If five or more patients out of a total of 25 were free of progressive disease a...

  9. Long-term safety and efficacy of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema of rosacea: results of a 1-year open-label study.

    Science.gov (United States)

    Moore, Angela; Kempers, Steven; Murakawa, George; Weiss, Jonathan; Tauscher, Amanda; Swinyer, Leonard; Liu, Hong; Leoni, Matthew

    2014-01-01

    Once-daily topical brimonidine tartrate (BT) gel 0.5% was shown to be efficacious and safe for the treatment of erythema of rosacea in previous studies including a 4-week treatment phase. In the present 1-year study, we aimed to assess the long-term safety and efficacy of the treatment. Subjects with moderate to severe erythema of rosacea were instructed to apply topical BT gel 0.5% once daily for 12 months. Severity of erythema and adverse events (AEs) were evaluated. Approximately 345 subject years of exposure to BT gel 0.5% was achieved in the study. The incidence of AEs and AEs judged to be related to the study drug was higher at the beginning and decreased over the course of the study. Similar safety profiles were observed between the subjects who had received or not received concomitant therapies for the inflammatory lesions of rosacea. Effect of topical BT gel 0.5% on erythema severity was observed after the first application and the durability of the effect was maintained until the end of the study at month 12, with no tachyphylaxis observed. In conclusion, once-daily topical BT gel 0.5% is safe and consistently effective for the long-term treatment of moderate to severe erythema of rosacea, even in the presence of concomitant therapies for the inflammatory lesions of rosacea.

  10. An open-label, in-use study assessing the warming sensation accompanying IFF Flavour 316282 and the acceptability and local tolerability of a syrup containing paracetamol and pseudoephedrine for the short-term treatment of symptoms of an upper respiratory tract infection

    Directory of Open Access Journals (Sweden)

    Rowland Furcha

    2015-03-01

    Full Text Available Objective: The primary objective was to assess the warming sensation caused by IFF Flavour 316282 in a syrup used for short-term treatment by patients suffering from nasal congestion and mild to moderate body pain, headache, fever or sore throat associated with an upper respiratory tract infection. Methods: A single cohort, single treatment arm, open-label study. Subjects received one 30 mL dose of syrup containing IFF Flavour 316282, paracetamol and pseudoephedrine and recorded onset and disappearance of any warming sensation in the mouth/throat. Subjects’ assessments of strength and appeal of the sensation, taste, texture and acceptability of the product was investigated using questionnaires. Results: A total of 56 subjects were included; 53 (94.6% experienced a warming sensation. The median duration of the warming sensation was 114 s (95% confidence interval: 87–120 s. All subjects rated the syrup as excellent, good or fair for treating their symptoms; 100% and 94.6% of subjects respectively described texture and taste as excellent, good or fair. There were no safety concerns, and the syrup was well tolerated. Most subjects liked the warming sensation. Conclusions: IFF Flavour 316282 in a syrup for treatment of upper respiratory tract infection symptoms is associated with a warming sensation. The syrup is well tolerated, safe and palatable.

  11. Mycoplasma hominis Meningitis in a 24 Week Premature Neonate: Case Report and Short Literature Review

    OpenAIRE

    Watson, Louise; Pang, Yee Min; Mitchell, Simon; Dodgson, Andrew

    2008-01-01

    Over the last 20-year period there have been fewer than 10 reported cases of Mycoplasma hominis central nervous system infection in either premature or full term infants. The optimum management of M hominis infection in premature infants is still unclear. We report the case of a premature infant with persistent central nervous system infection caused by M hominis treated successfully with intravenous chloramphenicol. Previous reports of M hominis central nervous infection and its management a...

  12. Multicentre, open-label, randomised, parallel-group, superiority study to compare the efficacy of octreotide therapy 40 mg monthly versus standard of care in patients with refractory anaemia due to gastrointestinal bleeding from small bowel angiodysplasias: a protocol of the OCEAN trial

    Science.gov (United States)

    van Geenen, E J M; Drenth, J P H

    2016-01-01

    Introduction Gastrointestinal angiodysplasias are an important cause of difficult-to-manage bleeding, especially in older patients. Endoscopic coagulation of angiodysplasias is the mainstay of treatment, but may be difficult for small bowel angiodysplasias because of the inability to reach them for endoscopic intervention. Some patients are red blood cell (RBC) transfusion dependent due to frequent rebleeding despite endoscopic treatment. In small cohort studies, octreotide appears to decrease the number of bleeding episodes in patients with RBC transfusion dependency due to gastrointestinal angiodysplasias. This trial will assess the efficacy of octreotide in decreasing the need for RBC transfusions and parenteral iron in patients with anaemia due to gastrointestinal bleeding of small bowel angiodysplasias despite endoscopic intervention. Study design Randomised controlled, superiority, open-label multicentre trial. Participants 62 patients will be included with refractory anaemia due to small bowel angiodysplasias, who are RBC transfusion or iron infusion dependent despite endoscopic intervention and oral iron supplementation. Intervention Patients will be randomly assigned (1:1) to standard care or 40 mg long-acting octreotide once every 4 weeks for 52 weeks, in addition to standard care. The follow-up period is 8 weeks. Main outcome measures The primary outcome is the difference in the number of blood and iron infusions between the year prior to inclusion and the treatment period of 1 year. Important secondary outcomes are the per cent change in the number of rebleeds from baseline to end point, adverse events and quality of life. Ethics and dissemination The trial received ethical approval from the Central Committee on Research Involving Human Subjects and from the local accredited Medical Research Ethics Committee of the region Arnhem-Nijmegen, the Netherlands (reference number: 2014-1433). Results will be published in a peer-reviewed journal and

  13. Effect of consuming a purple-fleshed sweet potato beverage on health-related biomarkers and safety parameters in Caucasian subjects with elevated levels of blood pressure and liver function biomarkers: a 4-week, open-label, non-comparative trial.

    Science.gov (United States)

    Oki, Tomoyuki; Kano, Mitsuyoshi; Watanabe, Osamu; Goto, Kazuhisa; Boelsma, Esther; Ishikawa, Fumiyasu; Suda, Ikuo

    2016-01-01

    An open-label study with one treatment arm was conducted to investigate changes in health-related biomarkers (blood pressure and liver enzyme activity) and the safety of 4 weeks of consuming a purple-fleshed sweet potato beverage in Caucasian subjects. Twenty healthy adults, 18-70 years of age, with a body mass index >25 kg/m(2), elevated blood pressure and elevated levels of liver function biomarkers consumed two cartons of purple-fleshed sweet potato beverage (125 ml, including 117 mg anthocyanin per carton) daily for 4 weeks. Hematology, serum clinical profile, dipstick urinalysis and blood pressure were determined before consumption, at 2 and 4 weeks of consumption and after a 2-week washout period. A trend was found toward lowering systolic blood pressure during the treatment period (p=0.0590). No significant changes were found in diastolic blood pressure throughout the study period. Systolic blood pressure was significantly lower after 4 weeks of consumption compared with before consumption (p=0.0125) and was significantly higher after the 2-week washout period compared with after consumption (p=0.0496). The serum alanine aminotransferase level significantly increased over time, but aspartate aminotransferase and γ-glutamyltransferase levels stayed within the normal range of reference values. Safety parameters of the blood and urine showed no clinically relevant changes. The consumption of a purple-fleshed sweet potato beverage for 4 weeks resulted in no clinically relevant changes in safety parameters of the blood and urine and showed a trend toward lowering systolic blood pressure. PMID:27508114

  14. Enzalutamide monotherapy: Phase II study results in patients with hormone-naive prostate cancer

    DEFF Research Database (Denmark)

    Tombal, Bertrand; Borre, Michael; Rathenborg, Per Zier;

    2013-01-01

    Background: Enzalutamide (ENZA) is an oral androgen receptor inhibitor that has been approved in the US and shown to increase overall survival by 4.8 months over a placebo (HR,0.63) in patients with metastatic castration resistant prostate cancer (CRPC) previously treated with docetaxel (Scher et...... al, N Engl J Med 2012;367:1187). Compared with bicalutamide in nonclinical studies, enzalutamide had higher androgen receptor– binding affinity, prevented nuclear translocation, showed no DNA binding, and induced apoptosis (Tran et al, Science 2009;324:787). In contrast to previous phase II and III....../dL). Methods: This was a 25-wk, open-label, single-arm study of patients with hormone-naïve, histologically confirmed prostate cancer (all stages) requiring hormonal treatment, an ECOG PS score of 0,and a life expectancy .1 y. All patients received ENZA 160 mg/d without concomitment castration. Primary endpoint...

  15. Antiviral activity of dolutegravir in subjects with failure on an integrase inhibitor-based regimen: week 24 phase 3 results from VIKING-3

    Science.gov (United States)

    Nichols, G; Mills, A; Grossberg, R; Lazzarin, A; Maggiolo, F; Molina, J; Pialoux, G; Wright, D; Ait-Khaled, M; Huang, J; Vavro, C; Wynne, B; Yeo, J

    2012-01-01

    Background VIKING-3 aimed to examine efficacy and safety of dolutegravir (DTG) 50 mg twice daily in patients with resistance to multiple ARV classes, including integrase inhibitors (INI). Methods RAL and/or EVG-resistant (current or historical) adult subjects with screening plasma HIV-1 RNA ≥500 c/mL and resistance to ≥2 other ART classes received open-label DTG 50 mg BID while continuing their failing regimen (without RAL/EVG). At Day 8 the background regimen was optimised and DTG continued. Activity of the optimized background regimen (OBR) was determined by Monogram Net Assessment. Primary endpoints were antiviral efficacy at Day 8 and Week 24. Results 183 subjects enrolled, 124 with INI-resistance at screening and 59 with historical (but no screening) resistance. Population was advanced: at BL, median CD4 140, prior ART 13 yrs, 56% CDC Class C; 79% had >2 NRTI, 75% >1 NNRTI, and 70% >2 PI resistance-associated mutations, and 61% had non-R5 HIV detected. Of the 114 subjects who had the opportunity to complete 24 weeks on study before data cutoff, 72 (63%) had 1 log HIV RNA decline of 2, respectively. Discontinuations due to adverse events were uncommon (6/183, 3%); the most common drug-related AEs were diarrhoea, nausea and headache, each reported in only 5% of subjects. Conclusion A majority of the highly treatment-experienced subjects in VIKING-3 achieved suppression with DTG-based therapy. Responses were associated with Baseline IN genotype but not OSS, highlighting the importance and independence of DTG antiviral activity. DTG had a low rate of discontinuation due to adverse events at 50 mg BID in this advanced patient population.

  16. 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

  17. 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...... of IFNa2 as well. The purpose of this COMBI-trial is to evaluate the safety and efficacy of CT with IFNa2 and ruxolitinib. Patients and Methods: At the time of data cutoff, a total of 30 pts >18 years with prefibrotic or hyperproliferative PMF (n=7), PV (n=20) or post-PV MF (PPV-MF) (n=3) with or without...

  18. 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.

  19. 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

  20. The efficacy and safety of bosentan therapy for Chinese patients with idiopathic pulmonary arterial hypertension:an open-label, prospective multicenter study%波生坦治疗特发性肺动脉高压患者的疗效及安全性

    Institute of Scientific and Technical Information of China (English)

    代立志; 蒋鑫; 王勇; 余再新; 姚桦; 王广义; 吴炳祥; 荆志成

    2011-01-01

    Objective To investigate the efficacy, safety and tolerance of bosentan, a dual endothelin receptor antagonist, in Chinese patients with idiopathic pulmonary arterial hypertension (IPAH).Methods Totally 79 IPAH patients (hemodynamic criteria confirmed by right heart catheterization) were included in this open-label, prospective multicenter study. Patients received 62. 5 mg of bosentan twice daily for the first 4 weeks, and then up-titrated to 125 mg twice daily for another 12 weeks. The primary end point was the change in exercise capacity showed by six-minute walk distance (6MWD) from baseline to 16 weeks. Secondary end points included the change in World Health Organization (WHO) functional class,Borg dyspnoea scale and systolic pulmonary artery pressure measured by echocardiography. Results The 6MWD increased from (343. 7 ± 93.7) meters at baseline to (397.5 ± 104. 4) meters after 16 weeks ( P <0. 01 ), WHO functional class and Borg dyspnoea scale were also significantly improved after 16 weeks therapy compared to baseline levels (all P <0. 01 ). Furthermore, the systolic pulmonary artery pressure was significantly decreased from (97.8±25.2) mm Hg (1 mm Hg=0. 133 kPa) to (92.8 ±29.5) mm Hg (P <0. 05) after 16 weeks bosentan treatment. There was no patient withdrawal from this study for safety consideration. Conclusion Bosentan therapy is well tolerated and can improve the exercise capacity and WHO functional class in Chinese IPAH patients.%目的 观察内皮素受体拮抗剂波生坦治疗中国特发性肺动脉高压患者的有效性、安全性及耐受性.方法 全国多中心Ⅳ期临床试验,共入选79例右心导管等技术确诊的新发特发性肺动脉高压患者,口服波生坦每日2次,每次62.5 mg,治疗4周后增至每日2次,每次125 mg至16周试验结束.分别在基线及治疗16周时记录6分钟步行距离,WHO肺高压功能分级、Borg呼吸困难评分及超声心动图评价资料.结果 波生坦治疗16

  1. Avaliação da tolerabilidade e do controle de ciclo de dois contraceptivos orais de baixa dose: estudo comparativo aberto Assessment of the tolerability and cycle control of two low-dose oral contraceptives: an open-label study

    Directory of Open Access Journals (Sweden)

    Edmund C. Baracat

    1998-06-01

    Full Text Available Realizou-se um estudo aberto comparativo em nove centros brasileiros para avaliar a tolerabilidade e o controle de ciclo obtido com o uso de dois contraceptivos orais de baixa dose contendo 20 mg etinilestradiol/75 mg gestodeno e 20 mg etinilestradiol/150 mg desogestrel, durante seis ciclos de tratamento. Foram selecionadas 167 mulheres saudáveis com vida sexual ativa (77 no grupo do gestodeno e 90 no grupo do desogestrel, das quais 138 completaram os seis ciclos de tratamento. Em um subgrupo de novas usuárias realizou-se também perfil lipídico e hemostático. Foram avaliados 867 ciclos no total. Ocorreu sangramento irregular em 4,6% dos ciclos com gestodeno e em 8,1% com desogestrel. A tolerabilidade a ambas preparações foi boa, mas houve significativamente mais náusea no grupo do desogestrel. O controle de ciclo foi bom com os dois contraceptivos, sendo que houve freqüência significativamente menor de sangramento irregular no grupo do gestodeno quando se leva em conta que todos os ciclos foram considerados. Não houve alterações clinicamente significativas no perfil hemostático. O perfil lipídico mostrou tendência a tornar-se mais favorável após seis ciclos de tratamento com as duas preparações. Não ocorreu alteração no peso médio das mulheres no grupo do gestodeno; no grupo do desogestrel houve aumento significativo no peso médio de aproximadamente 1 kg após seis meses de tratamento. A adesão ao tratamento foi boa com as duas preparações. Os resultados deste estudo mostram que preparações contendo baixa dose de gestodeno ou desogestrel associados a 20 mg de etinilestradiol são contraceptivos bem tolerados que permitem bom controle de ciclo, sem efeitos colaterais significantes.An open-label comparative study was conducted in nine centers in Brazil to evaluate the tolerability and cycle control of two low-dose oral contraceptives containing 20 mg ethynylestradiol/75 mg gestodene and 20 mg ethynylestradiol/150 mg

  2. Craving decrease with topiramate in outpatient treatment for cocaine dependence: an open label trial Diminuição da fissura com topiramato no tratamento ambulatorial para dependência de cocaína: um ensaio clínico aberto

    Directory of Open Access Journals (Sweden)

    Alessandra Diehl Reis

    2008-06-01

    Full Text Available OBJECTIVE: To evaluate anticraving action and tolerability of topiramate in cocaine user treatment. METHOD: Male users of inhaled cocaine which met criteria for cocaine dependence (Diagnostic and Statistical Manual of Mental Disorders, fourth edition were selected for outpatient 12-week, open label trial with topiramate; individual dosage ranged between 25-300 mg/day. Main clinical variables were abstinence rate, craving intensity, frequency and duration, adherence, dropouts, side effects and impulsivity measure through Barratt Impulsivity Scale. Patients received assertive strategic counseling for abstinence assistance and medication monitoring evaluation every two weeks. Comparative analysis was made with intention to treat, missing values were replaced (last observation carried forward, and significance level was 5%. RESULTS: Adherence to treatment was 57% (at least three evaluations, 32% dropped out (one evaluation. There were no severe side effects. Negative test average was 25.4% (31.2. Significant reduction in craving intensity and duration was observed in 25% of the sample. No statistical significant reduction in craving frequency was observed in 7.1%. Increase in frequency was observed in 10.7% and 82.1% did not present any variation. No significant statistical variations in Barratt Impulsivity Scale or in the total score were found in the final evaluation when compared to baseline. CONCLUSION: More randomized placebo-controlled trials with topiramate for cocaine dependants should be performed to evaluate preliminary evidence.OBJETIVO: Avaliar a ação anticraving e tolerabilidade do topiramato em usuários de cocaína. MÉTODO: Homens usuários de cocaína inalada que preenchiam critérios para dependência de cocaína (Manual Diagnóstico e Estatístico de Desordens Mentais, quarta edição foram selecionados para 12 semanas de tratamento ambulatorial, em ensaio clínico aberto com topiramato; dosagens escalonadas entre 25-300 mg

  3. 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

  4. An open-label study on the safety and efficacy of paliperidone extended-release in non-acute schizophrenic patients%帕利哌酮缓释片治疗非急性期精神分裂症疗效及安全性的开放性研究

    Institute of Scientific and Technical Information of China (English)

    张鸿燕; 舒良; 郝晓楠; 王雪芹; 刘琦; 李玲芝; 董继承; 张晋碚; 李洁; 许秀峰

    2012-01-01

    目的 评价可变剂量帕利哌酮缓释片治疗既往口服抗精神病药缺乏疗效或无法耐受而需换药的非急性期精神分裂症患者的疗效及安全性.方法 本研究为非随机、单组、为期12周的多中心的开放性临床研究,共纳入405例患者.主要疗效指标为治疗第12周末阳性和阴性症状量表( PANSS)评分较基线的变化.次要疗效指标包括:临床总体印象-严重度量表(CGI-S)、个人和社会功能量表(PSP).安全性评价包括不良反应记录、锥体外系症状评定量表(ESRS)、实验室及生命体征监测等.结果 PANSS总分由基线的(70.1±19.3)分下降至治疗终点的(48.1±15.7)分(P<0.01),CGI-S由基线的(4.1±1.2)分下降至治疗终点的(2.5±1.1)分(P<0.01),PSP总分由基线的(58.6±14.9)分提高至治疗终点的(74.5±13.4)分(P<0.01).发生率>5%的不良反应有:锥体外系反应(39.0%)、失眠(6.5%)和过度镇静(5.5%),ESRS总分由基线的(13.0±2.1)分下降至治疗终点的(12.6±1.6)分(P<0.01).平均体质量治疗终点较基线增加(0.2±3.5)kg (P <0.05).结论 换用可变剂量帕利哌酮缓释片对既往抗精神病药疗效不佳或耐受性不佳的非急性期精神分裂症患者疗效肯定,并具有较好安全性和耐受性.%Objective To explore the tolerability, safety and efficacy in adult non-acute schizophrenic patients after switching to flexibly doses of paliperidone extended-release ( paliperidone ER),for lack of efficacy,safety or tolerability with their previous oral antipsychotic.Methods In this nonrandomized,single arm,multi-center,12-week and open-label study,the primary efficacy measure was the total score changes of the Positive and Negative Syndrome Scale (PANSS),and the Clinical Global Impression-Severity Scale (CGI-S),Personal and Social Performance Scale (PSP) were adopted as secondary efficacy measures. The safety evaluation included monitoring adverse events,Extrapyramidal Symptom Rating

  5. Moon Phases

    Science.gov (United States)

    Riddle, Bob

    2010-01-01

    When teaching Moon phases, the focus seems to be on the sequence of Moon phases and, in some grade levels, how Moon phases occur. Either focus can sometimes be a challenge, especially without the use of models and observations of the Moon. In this month's column, the author describes some of the lessons that he uses to teach the phases of the Moon…

  6. Impact of 24 Weeks of Resistance and Endurance Exercise on Glucose Tolerance in Persons with Multiple Sclerosis

    OpenAIRE

    Wens, Inez; Hansen, Dominique; Verboven, Kenneth; Deckx, Nathalie; KOSTEN, Lauren; STEVENS, An; Cools, Nathalie; OP 'T EIJNDE, Bert

    2015-01-01

    Background: Recently, the authors reported an elevated prevalence of impaired glucose tolerance in individuals with multiple sclerosis (MS), compared with matched healthy controls, indicating metabolic defects that may increase comorbidity. MS also leads to a more inactive lifestyle, increasing the likelihood to develop fat accumulation, muscle wasting/weakness, and exercise intolerance. In other populations, these health complications can partly be reversed by physical exercise. Object...

  7. Virologic and immunologic outcomes after 24 weeks in HIV type 1-infected adolescents receiving highly active antiretroviral therapy

    NARCIS (Netherlands)

    Flynn, PM; Rudy, BJ; Douglas, SD; Lathey, J; Spector, SA; Martinez, J; Silio, M; Belzer, M; Friedman, L; D'Angelo, L; McNamara, J; Hodge, J; Hughes, MD; Lindsey, JC

    2004-01-01

    Background. Adolescents represent the fastest growing demographic group of new human immunodeficiency virus (HIV) infections in the United States. At present, there is little information available about their response to therapy. Methods. We studied 120 adolescents infected via high-risk behaviors w

  8. 24 weeks of Pilates-aerobic and educative training to improve body fat mass in elderly Serbian women

    Directory of Open Access Journals (Sweden)

    Rutjes AWS

    2014-04-01

    Full Text Available Anne WS Rutjes,1 Marcello Di Nisio2,31Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; 2Department of Medical, Oral, and Biotechnological Sciences, University G D'Annunzio of Chieti-Pescara, Chieti, Italy; 3Department of Vascular Medicine, Academic Medical Center, Amsterdam, the NetherlandsWe read with interest the article by Ruiz-Montero et al, in which the authors used a before-and-after study design to examine changes in body composition (fat mass and lean body mass related to an aerobic-Pilates program in elderly Serbian women.1 The authors concluded that "a combined program of aerobic and Pilates, carried out under the supervision of an instructor, at least twice a week, produces health benefits in functionally independent women over the age of 60". This conclusion is overly optimistic and not supported by the evidence provided. View original paper by Ruiz-Montero and colleagues.

  9. 24 weeks of Pilates-aerobic and educative training to improve body fat mass in elderly Serbian women

    OpenAIRE

    Rutjes AWS; Di Nisio M

    2014-01-01

    Anne WS Rutjes,1 Marcello Di Nisio2,31Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; 2Department of Medical, Oral, and Biotechnological Sciences, University G D'Annunzio of Chieti-Pescara, Chieti, Italy; 3Department of Vascular Medicine, Academic Medical Center, Amsterdam, the NetherlandsWe read with interest the article by Ruiz-Montero et al, in which the authors used a before-and-after study design to examine changes in body composition (fat mass and...

  10. 24-weeks Pilates-aerobic and educative training to improve body fat mass in elderly Serbian women

    OpenAIRE

    Ruiz-Montero PJ; Castillo-Rodriguez A; Mikalački M; Nebojsa Č; Korovljev D

    2014-01-01

    Pedro Jesús Ruiz-Montero,1 Alfonso Castillo-Rodriguez,2 Milena Mikalacki,3 Čokorilo Nebojsa,3 Darinka Korovljev31Department of Physical Education and Sport, Faculty of Physical Activity and Sport, University of Granada, Granada, Spain; 2Faculty of Sport, University of Pablo de Olavide, Seville, Spain; 3Faculty of Sport and Physical Education, University of Novi Sad, Novi Sad, SerbiaBackground: The purpose of this study was to examine the differences in anthropometric measurements ...

  11. The Collaborative Lithium Trials (CoLT: specific aims, methods, and implementation

    Directory of Open Access Journals (Sweden)

    Hooper Stephen R

    2008-08-01

    Full Text Available Abstract Background Lithium is a benchmark treatment for bipolar illness in adults. However, there has been relatively little methodologically stringent research regarding the use of lithium in youth suffering from bipolarity. Methods Under the auspices of the Best Pharmaceuticals for Children Act (BPCA, a Written Request (WR pertaining to the study of lithium in pediatric mania was issued by the United States Food and Drug Administration (FDA to the National Institute of Child Health and Human Development (NICHD in 2004. Accordingly, the NICHD issued a Request for Proposals (RFP soliciting submissions to pursue this research. Subsequently, the NICHD awarded a contract to a group of investigators in order to conduct these studies. Results The Collaborative Lithium Trials (CoLT investigators, the BPCA-Coordinating Center, and the NICHD developed protocols to provide data that will: (1 establish evidence-based dosing strategies for lithium; (2 characterize the pharmacokinetics and biodisposition of lithium; (3 examine the acute efficacy of lithium in pediatric bipolarity; (4 investigate the long-term effectiveness of lithium treatment; and (5 characterize the short- and long-term safety of lithium. By undertaking two multi-phase trials rather than multiple single-phase studies (as was described in the WR, the feasibility of the research to be undertaken was enhanced while ensuring all the data outlined in the WR would be obtained. The first study consists of: (1 an 8-week open-label, randomized, escalating dose Pharmacokinetic Phase; (2 a 16-week Long-Term Effectiveness Phase; (3 a 28-week double-blind Discontinuation Phase; and (4 an 8-week open-label Restabilization Phase. The second study consists of: (1 an 8-week, double-blind, parallel-group, placebo-controlled Efficacy Phase; (2 an open-label Long-Term Effectiveness lasting either 16 or 24 weeks (depending upon blinded treatment assignment during the Efficacy Phase; (3 a 28-week double

  12. Phase 1 trial of vocimagene amiretrorepvec and 5-fluorocytosine for recurrent high-grade glioma.

    Science.gov (United States)

    Cloughesy, Timothy F; Landolfi, Joseph; Hogan, Daniel J; Bloomfield, Stephen; Carter, Bob; Chen, Clark C; Elder, J Bradley; Kalkanis, Steven N; Kesari, Santosh; Lai, Albert; Lee, Ian Y; Liau, Linda M; Mikkelsen, Tom; Nghiemphu, Phioanh Leia; Piccioni, David; Walbert, Tobias; Chu, Alice; Das, Asha; Diago, Oscar R; Gammon, Dawn; Gruber, Harry E; Hanna, Michelle; Jolly, Douglas J; Kasahara, Noriyuki; McCarthy, David; Mitchell, Leah; Ostertag, Derek; Robbins, Joan M; Rodriguez-Aguirre, Maria; Vogelbaum, Michael A

    2016-06-01

    Toca 511 (vocimagene amiretrorepvec) is an investigational nonlytic, retroviral replicating vector (RRV) that delivers a yeast cytosine deaminase, which converts subsequently administered courses of the investigational prodrug Toca FC (extended-release 5-fluorocytosine) into the antimetabolite 5-fluorouracil. Forty-five subjects with recurrent or progressive high-grade glioma were treated. The end points of this phase 1, open-label, ascending dose, multicenter trial included safety, efficacy, and molecular profiling; survival was compared to a matching subgroup from an external control. Overall survival for recurrent high-grade glioma was 13.6 months (95% confidence interval, 10.8 to 20.0) and was statistically improved relative to an external control (hazard ratio, 0.45; P = 0.003). Tumor samples from subjects surviving more than 52 weeks after Toca 511 delivery disproportionately displayed a survival-related mRNA expression signature, identifying a potential molecular signature that may correlate with treatment-related survival rather than being prognostic. Toca 511 and Toca FC show excellent tolerability, with RRV persisting in the tumor and RRV control systemically. The favorable assessment of Toca 511 and Toca FC supports confirmation in a randomized phase 2/3 trial (NCT02414165). PMID:27252174

  13. Antiviral activity of dolutegravir in subjects with failure on an integrase inhibitor-based regimen: week 24 phase 3 results from VIKING-3

    Directory of Open Access Journals (Sweden)

    Mills A

    2012-11-01

    Full Text Available Background VIKING-3 aimed to examine efficacy and safety of dolutegravir (DTG 50 mg twice daily in patients with resistance to multiple ARV classes, including integrase inhibitors (INI. Methods RAL and/or EVG-resistant (current or historical adult subjects with screening plasma HIV-1 RNA ≥500 c/mL and resistance to ≥2 other ART classes received open-label DTG 50 mg BID while continuing their failing regimen (without RAL/EVG. At Day 8 the background regimen was optimised and DTG continued. Activity of the optimized background regimen (OBR was determined by Monogram Net Assessment. Primary endpoints were antiviral efficacy at Day 8 and Week 24. Results 183 subjects enrolled, 124 with INI-resistance at screening and 59 with historical (but no screening resistance. Population was advanced: at BL, median CD4 140, prior ART 13 yrs, 56% CDC Class C; 79% had >2 NRTI, 75% >1 NNRTI, and 70% >2 PI resistance-associated mutations, and 61% had non-R5 HIV detected. Of the 114 subjects who had the opportunity to complete 24 weeks on study before data cutoff, 72 (63% had <50 c/mL RNA at Week 24 (SNAPSHOT algorithm. Mean HIV RNA declined by 1.4 log10 c/mL (95% CI: 1.3, 1.5; p < 0.001 at Day 8; response differed by genotype pathway (Table. In subjects with Q148 pathway mutations, virologic response decreased with increasing number of secondary mutations. Background overall susceptibility score (OSS was not associated with Wk 24 response: % <50 c/mL were 83%, 63%, 59% and 69% for OSS 0, 1, 2 and >2, respectively. Discontinuations due to adverse events were uncommon (6/183, 3%; the most common drug-related AEs were diarrhoea, nausea and headache, each reported in only 5% of subjects. Conclusion A majority of the highly treatment-experienced subjects in VIKING-3 achieved suppression with DTG-based therapy. Responses were associated with Baseline IN genotype but not OSS, highlighting the importance and independence of DTG antiviral activity. DTG had a low rate

  14. Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the phase 3 BENEFIT trial

    DEFF Research Database (Denmark)

    Kappos, Ludwig; Freedman, Mark S; Polman, Chris H;

    2009-01-01

    with interferon beta-1b on time to clinically definite multiple sclerosis (CDMS) and other disease outcomes, including disability progression. METHODS: Patients with a first event suggestive of multiple sclerosis and a minimum of two clinically silent lesions in MRI were randomly assigned to receive...... interferon beta-1b 250 microg (n=292; early treatment) or placebo (n=176; delayed treatment) subcutaneously every other day for 2 years, or until diagnosis of CDMS. All patients were then eligible to enter a prospectively planned follow-up phase with open-label interferon beta-1b up to a maximum of 5 years...... 125 in both groups. No significant differences in other disability related outcomes were recorded. Frequency and severity of adverse events remained within the established safety and tolerability profile of interferon beta-1b. INTERPRETATION: Effects on the rate of conversion to CDMS and the...

  15. An open, randomized, parallel-group study to compare the efficacy and safety profile of inhaled human insulin (exubera) with meformin as adjunctive therapy in patients with type 2 diabetes poorly controlled on a sulfonylurea: response to mikhail and cope

    DEFF Research Database (Denmark)

    Barnett, Anthony H.; Dreyer, Manfred; Lange, Peter;

    2006-01-01

    OBJECTIVE: To compare the efficacy and safety profile of adding inhaled human insulin (INH; Exubera) or metformin to sulfonylurea monotherapy in patients with poorly controlled type 2 diabetes. RESEARCH DESIGN AND METHODS: We performed an open-label, parallel, 24-week, multicenter trial. At week -1...

  16. An open, randomized, parallel-group study to compare the efficacy and safety profile of inhaled human insulin (Exubera) with glibenclamide as adjunctive therapy in patients with type 2 diabetes poorly controlled on metformin

    DEFF Research Database (Denmark)

    Barnett, AH; Dreyer, M; Lange, Peter;

    2006-01-01

    OBJECTIVE: To compare the efficacy and safety profile of adding inhaled human insulin (INH) (Exubera) or glibenclamide to metformin monotherapy in patients with poorly controlled type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted an open-label, parallel, 24-week multicenter trial. Patients...

  17. Phase transitions

    CERN Document Server

    Solé, Ricard V

    2011-01-01

    Phase transitions--changes between different states of organization in a complex system--have long helped to explain physics concepts, such as why water freezes into a solid or boils to become a gas. How might phase transitions shed light on important problems in biological and ecological complex systems? Exploring the origins and implications of sudden changes in nature and society, Phase Transitions examines different dynamical behaviors in a broad range of complex systems. Using a compelling set of examples, from gene networks and ant colonies to human language and the degradation o

  18. Venus Phasing.

    Science.gov (United States)

    Riddle, Bob

    1997-01-01

    Presents a science activity designed to introduce students to the geocentric and heliocentric models of the universe. Helps students discover why phase changes on Venus knocked Earth out of the center of the universe. (DKM)

  19. Phase 1 Study of Erlotinib Plus Radiation Therapy in Patients With Advanced Cutaneous Squamous Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Heath, C. Hope; Deep, Nicholas L.; Nabell, Lisle; Carroll, William R.; Desmond, Renee; Clemons, Lisa; Spencer, Sharon; Magnuson, J. Scott [Division of Otolaryngology–Head and Neck Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama (United States); Rosenthal, Eben L., E-mail: oto@uab.edu [Division of Otolaryngology–Head and Neck Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama (United States)

    2013-04-01

    Purpose: To assess the toxicity profile of erlotinib therapy combined with postoperative adjuvant radiation therapy in patients with advanced cutaneous squamous cell carcinoma. Methods and Materials: This was a single-arm, prospective, phase 1 open-label study of erlotinib with radiation therapy to treat 15 patients with advanced cutaneous head-and-neck squamous cell carcinoma. Toxicity data were summarized, and survival was analyzed with the Kaplan-Meier method. Results: The majority of patients were male (87%) and presented with T4 disease (93%). The most common toxicity attributed to erlotinib was a grade 2-3 dermatologic reaction occurring in 100% of the patients, followed by mucositis (87%). Diarrhea occurred in 20% of the patients. The 2-year recurrence rate was 26.7%, and mean time to cancer recurrence was 10.5 months. Two-year overall survival was 65%, and disease-free survival was 60%. Conclusions: Erlotinib and radiation therapy had an acceptable toxicity profile in patients with advanced cutaneous squamous cell carcinoma. The disease-free survival in this cohort was comparable to that in historical controls.

  20. A North American brain tumor consortium phase II study of Poly-ICLC for adult patients with recurrent anaplastic gliomas

    Science.gov (United States)

    Butowski, Nicholas; Lamborn, Kathleen R.; Lee, Bee L; Prados, Michael D.; Cloughesy, Timothy; DeAngelis, Lisa M.; Abrey, Lauren; Fink, Karen; Lieberman, Frank; Mehta, Minesh; Robins, H. Ian; Junck, Larry; Salazar, Andres M.; Chang, Susan M.

    2011-01-01

    Purpose This phase II study was designed to determine the objective response rate and 6-month progression free survival of adult patients with recurrent supratentorial anaplastic glioma when treated with the immune modulator, polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC). Methods and Materials This was an open-labeled, single arm phase II study. Patients were treated with poly-ICLC alone. Patients may have had treatment for no more than two prior relapses. Treatment with poly-ICLC continued until tumor progression. Results 55 patients were enrolled in the study. 10 were ineligible after central review of pathology. 11% of patients (5 of 45) had a radiographic response. Time to progression was known for 39 patients and 6 remain on treatment. The estimated 6-month progression free survival was 24%. The median survival time was 43 weeks. Conclusions Poly-ICLC was well tolerated, but there was no improvement in 6-month progression free survival compared to historical database nor was there an encouraging objective radiographic response rate. Based on this study, poly-ICLC does not improve 6moPFS in patients with recurrent anaplastic gliomas but may be worth further study in combination with agents such as temozolomide. PMID:18850068

  1. Phase Vocoder

    Directory of Open Access Journals (Sweden)

    J.L. Flanagan

    2013-08-01

    Full Text Available A vocoder technique is described in which speech signals are represented by their short-time phase and amplitude spectra. A complete transmission system utilizing this approach is simulated on a digital computer. The encoding method leads to an economy in transmission bandwidth and to a means for time compression and expansion of speech signals.

  2. A phase II study of Givinostat in combination with hydroxycarbamide in patients with polycythaemia vera unresponsive to hydroxycarbamide monotherapy.

    Science.gov (United States)

    Finazzi, Guido; Vannucchi, Alessandro M; Martinelli, Vincenzo; Ruggeri, Marco; Nobile, Francesco; Specchia, Giorgina; Pogliani, Enrico Maria; Olimpieri, Odoardo Maria; Fioritoni, Giuseppe; Musolino, Caterina; Cilloni, Daniela; Sivera, Piera; Barosi, Giovanni; Finazzi, Maria Chiara; Di Tollo, Silvia; Demuth, Tim; Barbui, Tiziano; Rambaldi, Alessandro

    2013-06-01

    Givinostat, a histone-deacetylase inhibitor (HDACi), inhibits proliferation of cells bearing the JAK2 V617F mutation and has shown significant activity with good tolerability in patients with chronic myeloproliferative neoplasms (MPN). In this multicentre, open-label, phase II study, 44 patients with polycythaemia vera (PV), unresponsive to the maximum tolerated doses (MTD) of hydroxycarbamide (HC), were treated with Givinostat (50 or 100 mg/d) in combination with MTD of HC. The European LeukaemiaNet response criteria were used to assess the primary endpoint after 12 weeks of treatment. Complete or partial response was observed in 55% and 50% of patients receiving 50 or 100 mg of Givinostat, respectively. Control of pruritus was observed in 64% and 67% of patients in the 50 and 100 mg groups, respectively. The combination of Givinostat and HC was well tolerated: eight patients (18%) discontinued, four in each treatment arm; grade 3 adverse events were reported in one patient (4·5%) in each treatment arm. The combined use of Givinostat and HC was safe and clinically effective in HC-unresponsive PV patients. PMID:23573950

  3. THE SAFETY OF HAEMOPHILUS INFLUENZAE TYPE B/POLYRIBOSYLRIBITOL PHOSPHATE-TETANUS (HIB/PRP-T VACCINE, PHASE I STUDY

    Directory of Open Access Journals (Sweden)

    Kusnandi Rusmil

    2015-09-01

    Full Text Available Objective: To assess the safety and immunogenicity of the Haemophilus influenzae type b/polyribosylribitol phosphate-Tetanus (Hib/PRP-T liquid vaccine in healthy adults. Methods: An open label prospective intervention phase I study was conducted in Dr. Hasan Sadikin General Hospital from November to December 2010. Healthy adults aged 18−40 years were eligible to participate. Participants received one dose of Hib/PRP-T liquid vaccine. Blood samples were taken before, 4 days, and 1 month after vaccination. For a 28-day period following vaccination, solicited adverse events were recorded in the subjects’ diary and assessed afterward. Results: No local reactions or immediate systemic events were observed during the 30-minute period after immunization. There were no serious local or systemic reactions in this study. All of local and systemic reactions observed were slight, transient, self-limiting, and lasting no more than 72 hours after the administration of the vaccine. These reactions resolved without any medical intervention. Hematological and biochemical indices before and 4 days after vaccination were in normal limits. All subjects reached protective levels of antibodies (seroprotectivity against Hib. All subjects demonstrated antibodies performing high bactericidal activities 1 month after immunization. Conclusions: This study demonstrates that liquid Hib/PRP-T vaccine is highly immunogenic and beneficially safe when administered to healthy adults.

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

    Science.gov (United States)

    Kim, Youn H; Duvic, Madeleine; Obitz, Erik; Gniadecki, Robert; Iversen, Lars; Osterborg, Anders; Whittaker, Sean; Illidge, Timothy M; Schwarz, Thomas; Kaufmann, Roland; Cooper, Kevin; Knudsen, Kim M; Lisby, Steen; Baadsgaard, Ole; Knox, Susan J

    2007-06-01

    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 [SS], n = 9) received 17 weekly infusions of zanolimumab (early-stage patients, 280 and 560 mg; advanced-stage patients, 280 and 980 mg). The primary end point was objective response (OR) as assessed by composite assessment of index lesion disease activity score. Secondary end points included physician's global assessment (PGA), time to response, response duration, and time to progression. ORs were recorded for patients in both CTCL types (MF, 13 ORs; SS, 2 ORs). In the high-dose groups (560 and 980 mg dose groups), a response rate of 56% was obtained with a median response of 81 weeks. Adverse events reported most frequently included low-grade infections and eczematous dermatitis. Zanolimumab showed marked clinical efficacy in the treatment of patients with refractory MF, with early onset of response, high response rate, and durable responses. The treatment was well tolerated with no dose-related toxicity other than the targeted depletion of peripheral T cells. A pivotal study has been initiated based on these findings.

  5. Phase I randomised clinical trial of an HIV-1(CN54, clade C, trimeric envelope vaccine candidate delivered vaginally.

    Directory of Open Access Journals (Sweden)

    David J Lewis

    Full Text Available UNLABELLED: We conducted a phase 1 double-blind randomised controlled trial (RCT of a HIV-1 envelope protein (CN54 gp140 candidate vaccine delivered vaginally to assess immunogenicity and safety. It was hypothesised that repeated delivery of gp140 may facilitate antigen uptake and presentation at this mucosal surface. Twenty two healthy female volunteers aged 18-45 years were entered into the trial, the first receiving open-label active product. Subsequently, 16 women were randomised to receive 9 doses of 100 µg of gp140 in 3 ml of a Carbopol 974P based gel, 5 were randomised to placebo solution in the same gel, delivered vaginally via an applicator. Participants delivered the vaccine three times a week over three weeks during one menstrual cycle, and were followed up for two further months. There were no serious adverse events, and the vaccine was well tolerated. No sustained systemic or local IgG, IgA, or T cell responses to the gp140 were detected following vaginal immunisations. Repeated vaginal immunisation with a HIV-1 envelope protein alone formulated in Carbopol gel was safe, but did not induce local or systemic immune responses in healthy women. TRIAL REGISTRATION: ClinicalTrials.gov NCT00637962.

  6. Phase 1 study in Japan of siltuximab, an anti-IL-6 monoclonal antibody, in relapsed/refractory multiple myeloma.

    Science.gov (United States)

    Suzuki, Kenshi; Ogura, Michinori; Abe, Yu; Suzuki, Tatsuya; Tobinai, Kensei; Ando, Kiyoshi; Taniwaki, Masafumi; Maruyama, Dai; Kojima, Minoru; Kuroda, Junya; Achira, Meguru; Iizuka, Koho

    2015-03-01

    Siltuximab, a chimeric monoclonal antibody with high affinity and specificity for interleukin-6, has been shown to enhance anti-multiple myeloma activity of bortezomib and corticosteroid in vitro. We evaluated the safety, pharmacokinetics, immunogenicity, and antitumor effect of siltuximab in combination with bortezomib and dexamethasone in Japanese patients with relapsed or refractory multiple myeloma. This open-label, phase 1, dose-escalating study used two doses of siltuximab: 5.5 and 11.0 mg/kg (administered on day 1 of each 21-day cycle). In total, nine patients were treated. The most common grade 3/4 adverse events, lymphopenia (89 %) and thrombocytopenia (44 %), occurred in patients receiving both doses of siltuximab; however, no dose-limiting toxicities (DLTs) were observed. Following intravenous administration of siltuximab at 5.5 and 11.0 mg/kg, the maximum serum concentration and the area under the curve from 0 to 21 days and from 0 to infinity increased in an approximately dose-proportional manner. Mean half-life, total systemic clearance, and volume of distribution were similar at doses of 5.5 and 11.0 mg/kg. Across both doses, six of the nine patients had complete or partial response (22 and 44 %, respectively). In conclusion, as no DLT was observed, the recommended dose for this combination is 11.0 mg/kg once every 3 weeks. The study is registered at http://www.clinicaltrials.gov as NCT01309412. PMID:25655379

  7. Tipepidine in adolescent patients with depression: a 4 week, open-label, preliminary study

    Directory of Open Access Journals (Sweden)

    Sasaki T

    2014-05-01

    Full Text Available Tsuyoshi Sasaki,1,2 Kenji Hashimoto,3 Masumi Tachibana,1 Tsutomu Kurata,1 Hiroshi Kimura,2 Hideki Komatsu,2 Masatomo Ishikawa,2 Tadashi Hasegawa,2 Akihiro Shiina,1 Tasuku Hashimoto,2 Nobuhisa Kanahara,4 Tetsuya Shiraishi,2 Masaomi Iyo1–41Department 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, 4Division of Medical Treatment and Rehabilitation, Chiba University Center for Forensic Mental Health, Inohana, Chiba, JapanDepression in children and adolescents is a common, recurrent, and debilitating condition associated with increased psychosocial, and medical morbidity and mortality.1The global prevalence of depression in children and adolescents is 1%–2% and 3%–8%, respectively.2 Depressive symptoms are also associated with significant functional impairment in school and the work place (often requiring legal interventions,1–5 and an increased risk for substance abuse and suicide.6–9 Clinical guidelines suggest the use of two selective serotonin reuptake inhibitors (SSRI, namely fluoxetine and escitalopram, both of which are effective with generally acceptable safety profiles in the treatment of adolescent depression.10 Additionally, combination treatment with an SSRI and psychotherapy, typically cognitive behavioral therapy (CBT, has shown benefit in this cohort.10 However, caution is warranted since antidepressants therapy in children and adolescents is associated with increased rates of suicidal ideation11–13 and adverse effects, characterized by excessive emotional arousal or behavioral activation.14 These results highlight the need for new therapies in adolescent patients with depression, particularly therapies with fewer side effects.View original paper by Brent and Maalouf.

  8. Gabapentin adjunctive to risperidone or olanzapine in partially responsive schizophrenia: an open-label pilot study

    Directory of Open Access Journals (Sweden)

    Adel Gabriel

    2010-10-01

    Full Text Available Adel GabrielDepartments of Psychiatry and Community Health Sciences, University of Calgary, Alberta, CanadaBackground: There is a great need in the treatment of schizophrenia for a drug, or drug ­combinations, to improve clinical response with fewer serious side effects. The objective of this study was to explore the therapeutic effects and tolerability of the anticonvulsant gabapentin as an adjunctive in the treatment of patients with partially responsive schizophrenia.Methods: Ten consenting patients with a confirmed Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision diagnosis of schizophrenia were identified. All patients failed at least one 12-week treatment trial with risperidone or olanzapine. Gabapentin was added to ongoing antipsychotic treatment with olanzapine or risperidone for eight weeks. The primary outcome measure was the Positive and Negative Syndrome Scale (PANSS. Other scales included the Calgary Depression Scale (CDSS and the Abnormal Involuntary Movement Scale (AIMS. Repeated-measures multivariate analysis of variance was utilized to examine changes in outcome measures over time with adjunctive treatment with gabapentin.Results: There was a significant drop in the PANSS and CDSS scores at endpoint (week 8. There were no significant differences between the two treatment groups with regard to changes in all outcome measures or in AIMS score. The adjunctive treatments were well tolerated and side effects were transient.Conclusion: Gabapentin could be used successfully as an adjunct to novel antipsychotics in partially responsive schizophrenia. However, large controlled studies are needed to examine the effectiveness of gabapentin in psychotic disorders.Keywords: schizophrenia, refractory, adjunctive treatment, gabapentin, risperidone, olanzapine

  9. An open-label trial of risperidone and fluoxetine in children with autistic disorder

    Directory of Open Access Journals (Sweden)

    Desousa Avinash

    2010-01-01

    Full Text Available Objective: Various studies have shown the effectiveness of risperidone and fluoxetine in the management of behavioral problems in autism. Aim: The purpose of this study was to compare these two drugs in the management of behavioral problems in autism. Materials and Methods: Forty children with autism were divided into 2 groups in a 16-week open trial that compared these two drugs. Parents rated the children using the Aberrant Behavior Checklist (ABC and the Conners′ Parent Rating Scale - Revised (CPRS-R. The author rated the children using the Children′s Psychiatric Rating Scale and Clinical Global Impression (CGI Scale. Results: The risperidone group showed significant improvement in areas like irritability and hyperactivity, while the fluoxetine group showed significant improvement in speech deviance, social withdrawal and stereotypy. When the two drugs were compared, fluoxetine showed greater improvement in stereotypy, while both drugs showed improvement on the general autism scale; and on anger, hyperactivity and irritability scales. Conclusions : In this open trial, both drugs were well tolerated and appeared to be beneficial in the treatment of common behavioral problems in children with autism. Further controlled and double-blind studies in larger samples are warranted.

  10. The Effects of QEEG-Informed Neurofeedback in ADHD: An Open-Label Pilot Study

    OpenAIRE

    Arns, Martijn; Drinkenburg, Wilhelmus; Leon Kenemans, J.

    2012-01-01

    In ADHD several EEG biomarkers have been described before, with relevance to treatment outcome to stimulant medication. This pilot-study aimed at personalizing neurofeedback treatment to these specific sub-groups to investigate if such an approach leads to improved clinical outcomes. Furthermore, pre- and post-treatment EEG and ERP changes were investigated in a sub-group to study the neurophysiological effects of neurofeedback. Twenty-one patients with ADHD were treated with QEEG-informed ne...

  11. Fluvoxamine for the Treatment of Child and Adolescent Depression: An Open Label Trial

    Directory of Open Access Journals (Sweden)

    Ali Alavi

    2008-12-01

    Full Text Available "n Objective: "n Major depressive disorder is a severe disorder that has a significant impact on the psychological and social functioning of children and adolescents. Considering current limitations in the treatment of this disorder, the present study was performed to evaluate the efficacy of fluvoxamine in the treatment of children and adolescents with major depressive disorder. "nMethod: In an open trial, the efficacy of fluvoxamine (50-200 mg/d on children and adolescents with major depressive disorder or dysthymic disorder was evaluated using the "Children's Depression Inventory", the "Hamilton Anxiety Rating Scale", the "Children - Global Assessment Scale", the "Clinical Global Impression Scale", and the "Drug Side Effect Questionnaire" at the beginning and 2, 4, and 8 weeks after the beginning of the treatment. The frequency of suicidal ideas was evaluated as well. "nResults: Treatment with fluvoxamine caused statistically significant improvement in all of the above scales. The frequency of suicidal ideas decreased from 88.9 percent to zero after 8 weeks. No significant side effects were observed. "nConclusion: Fluvoxamine can be used as a safe and effective drug in the treatment of major depressive disorder and dysthymic disorder of children and adolescents.

  12. Fluvoxamine for the Treatment of Child and Adolescent Depression: An Open Label Trial

    OpenAIRE

    Ali Alavi; Zahra Sepehrmanesh; Fariba Arabgol

    2008-01-01

    "n Objective: "n Major depressive disorder is a severe disorder that has a significant impact on the psychological and social functioning of children and adolescents. Considering current limitations in the treatment of this disorder, the present study was performed to evaluate the efficacy of fluvoxamine in the treatment of children and adolescents with major depressive disorder. "nMethod: In an open trial, the efficacy of fluvoxamine (50-200 mg/d) on children and adolescents with major ...

  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

    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...

  14. INFLUENCE OF ACARBOSE ON POSTPRANDIAL DYSMETABOLISM: RESULTS OF AN OPEN-LABEL RANDOMIZED STUDY

    Directory of Open Access Journals (Sweden)

    A. Ya. Cherniak

    2015-09-01

    Full Text Available Aim. To evaluate postprandial changes of lipid and glucose profiles, inflammation markers levels and flow-mediated vasodilatation in patients with metabolic syndrome (MS and to estimate acarbose course treatment efficacy in glucose intolerant patients.Material and methods. A total of 114 MS patients (83 men, 31 women were examined, MS was associated with impaired glucose tolerance (IGT in 55 cases. At the first stage postpran- dial dynamics of flow-mediated dilation (FMD, lipid profile parameters, inflammation markers and insulin levels were estimated. At the second stage patients with MS and IGT (n=55 were randomly assigned to the two groups of treatment. Patients of the first group (n=28 had non-drug treatment. Patients of the second group (n=27 received acarbose 300 mg/day for 3 months in addition to recommendations for lifestyle change. 3 months later postprandial values of lipid and glucose profiles parameters, inflammation markers levels and FMD were reassessed. Results. MS patients with IGT revealed maximal disorders in metabolic parameters during postprandial period: increase in the plasma levels of total cholesterol by 6.1%, high density lipoproteins – by 1.7%, and triglycerides – by 27.87%, increase in atherogenic index by 4.8%, and plasma concentrations of glucose – by 54.7%, insulin – by 30.2%, HOMA index – by 73.3%, as well as concentrations of C-reactive protein (CRP – by 49.7%, tumor necrose factor alpha – by 20.8%, and interleukin-6 (IL-6 – by 51.9%. FMD decreased by 34.3%.After 12 weeks of the acarbose treatment we had revealed positive dynamics of studied indices in postprandial period as compared to an only non-drug management: levels of glucose in- creased by 24.1% vs 44.4%, insulin – by 14.4% vs 24.4%, CRP – by 19.9% vs 36.6%, IL-6 – by 25.1% vs 41.7%; postprandial FMD decreased by 18.9% vs 31.1%.Conclusion. Prescription of acarbose 300 mg/day for 12 weeks in glucose intolerant patients is characterized by less significant postprandial increase in insulin resistance, inflammation mark- ers (CRP and IL-6 levels, less decrease in flow-mediated vasodilatation with no influence on lipid metabolism parameters.

  15. INFLUENCE OF ACARBOSE ON POSTPRANDIAL DYSMETABOLISM: RESULTS OF AN OPEN-LABEL RANDOMIZED STUDY

    OpenAIRE

    A. Ya. Cherniak; I. M. Petrov; I V Medvedeva

    2015-01-01

    Aim. To evaluate postprandial changes of lipid and glucose profiles, inflammation markers levels and flow-mediated vasodilatation in patients with metabolic syndrome (MS) and to estimate acarbose course treatment efficacy in glucose intolerant patients.Material and methods. A total of 114 MS patients (83 men, 31 women) were examined, MS was associated with impaired glucose tolerance (IGT) in 55 cases. At the first stage postpran- dial dynamics of flow-mediated dilation (FMD), lipid profile pa...

  16. Baclofen as relapse prevention in the treatment of Gamma- Hydroxybutyrate (GHB) dependence: an open label study

    NARCIS (Netherlands)

    Kamal, R.M.; Schellekens, A.F.A.; Jong, C.A.J. de; Dijkstra, B.A.

    2015-01-01

    BACKGROUND: GHB dependence is a growing health problem in several western countries, especially the Netherlands. Attempts to stop using GHB are often followed by relapse shortly after successful detoxification. Craving for GHB use and co-morbid psychiatric symptom levels are thought to be the major

  17. An open-label study of escitalopram in body dysmorphic disorder

    OpenAIRE

    Phillips, Katharine A.

    2006-01-01

    Body dysmorphic disorder (BDD) is a relatively common and impairing disorder. Selective serotonin reuptake inhibitors (SRIs) appear selectively efficacious for BDD, but pharmacotherapy research is limited, and escitalopram has not been studied. Fifteen subjects with BDD were treated with escitalopram and assessed with reliable and valid measures. BDD symptoms significantly improved (P < 0.001), and 73.3% (n = 11) of subjects were responders. Of the subjects, 46.7% were very much improved, and...

  18. Open Label Extension of ISIS 301012 (Mipomersen) to Treat Familial Hypercholesterolemia

    Science.gov (United States)

    2013-12-02

    Lipid Metabolism, Inborn Errors; Hypercholesterolemia, Autosomal Dominant; Hyperlipidemias; Metabolic Diseases; Hyperlipoproteinemia Type II; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Metabolic Disorder; Congenital Abnormalities; Hypercholesterolemia; Hyperlipoproteinemias; Dyslipidemias; Lipid Metabolism Disorders

  19. URINARY TRACT INFECTION IN CHILDREN WITH NEPHROTIC SYNDROME: A PROSPECTIVE OPEN LABELED STUDY

    Directory of Open Access Journals (Sweden)

    Rajendra

    2014-09-01

    Full Text Available : BACKGROUND: Nephrotic syndrome is an important chronic disorder in children in which prevalence of urinary tract infection (UTI is high. UTI may also be responsible for steroid resistance and relapse. UTI is an important but often undiagnosed condition in children with nephrotic syndrome. Hence the present study is being conducted. AIMS AND OBJECTIVES: The study is conducted to determine the clinical features of nephrotic syndrome and to evaluate the incidence, etiological agents, clinical features and the antibiotic sensitivity pattern of Urinary Tract Infections in children with Nephrotic Syndrome. MATERIAL & METHODS: The study was a Prospective hospital based study done by Stratified random sampling conducted on all the paediatric patients with a diagnosis of nephrotic syndrome attending the OPD and admitted to Paediatric hospital. Fifty children with diagnosis of Nephrotic Syndrome were studied. The specimen for urine culture was obtained carefully to prevent contamination by periurethral flora. A clean-catch midstream urine specimen was used. Contamination by periurethral and prepucial organisms was minimized by washing the genitalia. The specimen was directly collected in a sterile container. Prompt plating of the urine specimen, within one hour of collection was ensured. Identification of the organism to species level was done and antibiotic sensitivity pattern was also studied. RESULTS: Among the fifty children studied, boys were affected more than girls by Nephrotic syndrome with a ratio of 1.5:1. The mean age was 4.75 years. Urinary Tract Infection was detected in seventeen children (34%. The present study was statistically significant with p<0.001. The commonest Micro-organism isolated was Escherichia coli, followed by Staphylococcus aureus. Most of the Micro-organisms were sensitive to cephalosporins. CONCLUSION: Urinary Tract Infection is a significant infection detected in cases of Nephrotic Syndrome affecting one third of the cases. Early detection and prompt treatment with appropriate antibiotics will play a major role in preventing the morbidity and mortality as well as it avoids the relapse and facilitates early remission of Nephrotic Syndrome. High index of suspicion, early institution of appropriate antibiotics and aggressive management of infections can attenuate morbidity and mortality.

  20. Tinospora cordifolia stem supplementation in diabetic dyslipidemia: an open labelled randomized controlled trial

    OpenAIRE

    Kuhu Roy; Rumin Shah; Uma Iyer

    2015-01-01

    Background: Medicinal plants are powerful health promoting nutritional agents. Among the vast library of medicinal plants Tinospora cordifolia (Willd.) has been meagrely explored. It belongs to the family Menispermaceae and is a rich source of alkaloid and terpenes. It has hepatoprotective, antioxidant, immunostimulatory, hyperlipidemic, anticancer and antidiabetic properties. The stem contains berberine, palmatine, tembetarine, magnoflorine, tinosporin, tinocordifolin. The stem starch is hig...

  1. Tinospora cordifolia stem supplementation in diabetic dyslipidemia: an open labelled randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Kuhu Roy

    2015-08-01

    Full Text Available Background: Medicinal plants are powerful health promoting nutritional agents. Among the vast library of medicinal plants Tinospora cordifolia (Willd. has been meagrely explored. It belongs to the family Menispermaceae and is a rich source of alkaloid and terpenes. It has hepatoprotective, antioxidant, immunostimulatory, hyperlipidemic, anticancer and antidiabetic properties. The stem contains berberine, palmatine, tembetarine, magnoflorine, tinosporin, tinocordifolin. The stem starch is highly nutritive and digestive. In modern medicine it is called the magical rejuvenating herb owing to its properties to cure many diseases. The stem contains higher alkaloid content than the leaves because of which it is approved for medicinal usage. With a host of phytochemical properties present in the stem, it may hold potential to manage dyslipidemia and dysglycemia, which otherwise has been proven only in pre-clinical studies. Objective: To study the impact of tinospora cordifolia stem supplementation on the glycemic and lipemic profile of subjects with diabetic dyslipidemia. Methods: Type 2 diabetics with dyslipidemia on oral hypoglycemic agents were enrolled. Baseline data on medical history, family history of lifestyle diseases, duration of diabetes diagnosis, drug profile, anthropometric data, dietary data and physical activity data was obtained along with a fasting blood sample for estimating high sensitivity C reactive protein (hs-CRP, hepatic, renal, lipid profile and glycated hemoglobin. The participants were randomized into either of the two groups; intervention group (n=29 received 250mg of encapsulated mature stem of tinospora cordifolia pre meal twice a day along with prescribed dyslipidemic agent and control group (n=30 only on dyslipidemic agents for a period of 60 days. After 60 days all the parameters were re-assessed to analyse the impact of the intervention. Results: Majority of the subjects in both the arms were in the 50-60 years age bracket with a similar duration of diabetes, disease and drug profile. Tinospora cordifolia supplementation led to a significant decline in waist circumference (94.7 to 94.2cm, P 0.004, hip circumference (99.9 to 9.5cm, P 0.004, waist stature ratio (0.594 to 0.591, P 0.004 and systolic blood pressure (132.6 to 127.1mmHg, P 0.0017 vs. significant decline in hip circumference (100.02 to 99.7cm, P 0.01 and systolic blood pressure (134.5 to 130.1mmHg, P 0.0013 in controls. The intervention brought about a significant decline in hs-CRP (4.6 to 2.8mg/l, P 0.0007 and the prevalence of hs-CRP>3mg/l declined from 65.5% to 37.9% (P 0.037. Renal and hepatic parameters remained in the normal range. Decline in HbA1c, although non-significant, was more evident in the intervention arm (7.7 to 7.5%, P 0.09 than the controls (7.9 to 7.81%, P 0.52. Intervention led to significant reductions in total cholesterol, low density lipoprotein, triglycerides and very low density lipoprotein and among controls too, but of lesser intensity. The number of dyslipidemic features declined by 28.6% (P 0.0036 in the intervention arm and by 19.4% in controls (P 0.020. The prevalence of metabolic syndrome decreased by 13.73% from 68.9% to 55.17% in the intervention arm and reduced by 6.7% from 56.7% to 50% among controls. Conclusion: Tinospora cordifolia stem supplementation brought about more evident changes in the lipoprotein fractions, inflammatory markers and metabolic syndrome than the controls.

  2. Cold Therapy in Migraine Patients: Open-label, Non-controlled, Pilot Study

    Directory of Open Access Journals (Sweden)

    Serap Ucler

    2006-01-01

    Full Text Available Some patients with headache report that they have frequently used physical therapies such as application of cold to relieve their headache. There are only a few reported studies related to cold therapies in patients with migraine. In this study, we investigated the effect of cold application on migraine patients. Twenty-eight migraine patients were included. Cold therapy was administered to them by gel cap. Patients used this cap during their two migraine attacks. Before and after the cold therapy, headache severity was recorded by using visual analogue scale (VAS. Patients used this cap for 25 min in each application. They recorded their VAS score just after the therapy and 25 min, 1 h, 2 h and 3 h later. Two patients could not use this therapy due to side effects (one due to cold intolerance and one due to vertigo in both applications. Therefore, therapeutic efficacy was evaluated in 26 patients. Twenty-five minutes after treatment of the first attack, VAS score was decreased from 7.89 ± 1.93 to 5.54 ± 2.96 (P < 0.01. Twenty-five minutes after treatment of the second attack, VAS score was decreased from 7.7 ± 1.8 to 5.4 ± 3.55 (P < 0.01. Cold application alone may be effective in some patients suffering from migraine attacks. Its combination with conventional drugs should be investigated in future studies.

  3. A probiotic treatment containing Lactobacillus, Bifidobacterium and Enterococcus improves IBS symptoms in an open label trial

    Institute of Scientific and Technical Information of China (English)

    FAN Yu-jing; CHEN Shu-jie; YU Ying-cong; SI Jian-min; LIU Bin

    2006-01-01

    Objective: To evaluate the efficacy and safety of live combined Bifidobacterium, Lactobacillus and Enterococcus capsules in treatment of irritable bowel syndrome. Methods: Eighty-five patients [male 32, female 53; age (45.31±11.72) years]were given live combined Bifidobacterium, Lactobacillus and Enterococcus capsules 1260 mg/d t.i.d.×4 weeks. Syndrome scales were used to evaluate the efficacy in gastrointestinal syndrome. Fecal flora was also measured before and after the treatment. Six bacteria were cultured and the colony forming units were counted in stool. SPSS was used for data analysis. Results: Seventy-four patients finished the follow-up. No side-effect was found. For treatment of irritable bowel syndrome, the effective rate of live combined Bifidobacterium, Lactobacillus and Enterococcus capsules was 56.8% in the second week, 74.3% in the fourth week and 73.0% in the sixth week. Single symptom was improved, especially in abdominal pain and stool character. The probiotica containing live combined Bifidobacterium, Lactobacillus and Enterococcus could increase bifidobacterium count (P<0.01) and lactobacillus count (P<0.05); decrease bacteroides count (P<0.05) and enterococci count (P<0.01); No obvious changes were observed in clostridium difficile colonitis and enterobacteriaceae (P>0.05). Conclusion: The result of the study indicated that the administration of live combined Bifidobacterium, Lactobacillus and Enterococcus improved the symptom of irritable bowel syndrome and that there was a gradual increase of this effect. Thereafter conditions remained stable for 2 weeks. That improvement may be associated with alterations in gastrointestinal flora.

  4. AN OPEN LABEL PILOT STUDY TESTING THE ROLE OF CLASSICAL HOMEOPATHY IN CHRONIC ALLERGIC RHINITIS

    Directory of Open Access Journals (Sweden)

    S. Ghosh*, S. Das, M. Mundle Dishari Sengupta, Sk. Intaj Hossain, M. Koley and S. Saha

    2013-04-01

    Full Text Available ABSTRACT: Purpose: The prevalence of allergic rhinitis (AR is increasing at an alarming rate throughout the world. India has an estimated number of 15-20 million patients with allergic bronchial asthma and 30-80% of these suffer from AR. So, AR is considered as a major chronic respiratory disease due to its prevalence, impact on quality of life (QoL, work/school performance and productivity, economic burden and links with asthma. This research aims at testing the role of classical homeopathy in bringing changes in serum immunoglobulin E (IgE level and absolute eosinophil count (primary outcome measures and symptoms score and WHOQOL-BREF score related to AR (secondary outcome measures by comparing the pre-trial and post-trial data.

  5. Topical treatment of actinic keratoses with potassium dobesilate 5% cream. a preliminary open-label study

    Directory of Open Access Journals (Sweden)

    Cuevas P

    2011-02-01

    Full Text Available Abstract Background Fibroblast growth factor (FGF is involved in skin tumorigenesis: it promotes cell viability, induces angiogenesis and stimulates invasiveness. Dobesilate is a drug that blocks the activity of FGF. The primary objective was to evaluate the efficacy and tolerability of potassium dobesilate 5% cream in the treatment of actinic keratoses. Methods Potassium dobesilate 5% cream was applied twice daily for 16 weeks to actinic keratosis lesions in 30 patients. The lesions were evaluated clinically at an initial baseline visit, at intermediate visits, and at 16 weeks of treatment. Results The use of potassium dobesilate 5% cream for 16 weeks induced complete regression in 70% of evaluated actinic keratoses, corresponding to grade I, II and III clinical variants, and a partial response (at least 75% reduction of lesions in 20% of the cases. Conclusion Our preliminary trial shows that potassium dobesilate exerts anti-tumorigenic effects and may play a useful role in the chemoprevention of skin cancers.

  6. Efficacy of Solifenacin on Irritable Bowel Syndrome With Diarrhea: Open-label Prospective Pilot Trial

    OpenAIRE

    Fukushima, Yasushi; SuzukI, Hidekazu; Matsuzaki, Juntaro; Kiyosue, Arihiro; Hibi, Toshifumi

    2012-01-01

    Background/Aims Solifenacin, a muscarinic type 3 receptor antagonist, is used to treat overactive bladder in adults. The aim of this study is to examine the efficacy of solifenacin on the symptomatic relief of diarrhea predominant irritable bowel syndrome (IBS-D). Methods A total of 20 patients with IBS-D were enrolled. After a 2-week observation period, all participants received solifenacin for 6 weeks. Subsequently, the administration of solifenacin was discontinued and ramosetron, a seroto...

  7. An open labeled study to evaluate efficacy and safety of ampucare in patients with bedsore

    Directory of Open Access Journals (Sweden)

    Janardhan Singh

    2013-08-01

    Full Text Available Background: To evaluate efficacy and safety of ampucare, a polyherbal product, in patients with bedsore. Methods: One hundred patients, either sex, more than 18 years of age, with bedsore were divided in to two groups of 50 each. Group-I- Served as control- povidone iodine solution was applied locally on the bedsore, once daily. Group- II- Treatment group- ampucare lotion was applied locally, once daily. Primary end point was time to wound healing and secondary end point included reduction in wound surface area at day-7 and at treatment completion. Percent patients cured, improved, or treatment failure were noted. Depth of wound, % healing and adverse effects were recorded. Results: Application of ampucare in patients with bedsore resulted in rapid healing as compared to control group. Reduction in wound surface area was significant (p<0.01 in group-II. Maximum gain in thickness of granular tissue was observed in this group. In treatment group 68% patients showed excellent response as compared to 60 % in control group. Ampucare was well tolerated. Conclusions: Ampucare treatment markedly accelerates wound healing in patients with bedsore. [Int J Basic Clin Pharmacol 2013; 2(4.000: 371-374

  8. An open labeled study to evaluate efficacy and safety of ampucare in patients with bedsore

    OpenAIRE

    Janardhan Singh; Sukhbir Singh Sangwan; Jarnail Singh; Ram Chandar Siwach; Govind Shukla

    2013-01-01

    Background: To evaluate efficacy and safety of ampucare, a polyherbal product, in patients with bedsore. Methods: One hundred patients, either sex, more than 18 years of age, with bedsore were divided in to two groups of 50 each. Group-I- Served as control- povidone iodine solution was applied locally on the bedsore, once daily. Group- II- Treatment group- ampucare lotion was applied locally, once daily. Primary end point was time to wound healing and secondary end point included reduction in...

  9. An Open-Label Trial of Rituximab Therapy in Pulmonary Alveolar Proteinosis

    OpenAIRE

    Kavuru, Mani S.; Malur, Anagha; Marshall, Irene; Barbara P. Barna; Meziane, Moulay; Huizar, Isham; Dalrymple, Heidi; Karnekar, Reema; Thomassen, Mary Jane

    2011-01-01

    Rituximab, a monoclonal antibody directed against the B-lymphocyte antigen CD20, has shown promise in several autoimmune disorders. Pulmonary Alveolar Proteinosis (PAP) is an autoimmune disorder characterized by autoantibodies to Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF).

  10. Occupational therapy in spinocerebellar ataxia type 3: an open-label trial

    Directory of Open Access Journals (Sweden)

    R.C.R. Silva

    2010-06-01

    Full Text Available Occupational therapy (OT is a profession concerned with promoting health and well-being through occupation, by enabling handicapped people to participate in the activities of everyday life. OT is part of the clinical rehabilitation of progressive genetic neurodegenerative diseases such as spinocerebellar ataxias; however, its effects have never been determined in these diseases. Our aim was to investigate the effect of OT on both physical disabilities and depressive symptoms of spinocerebellar ataxia type 3 (SCA3 patients. Genomically diagnosed SCA3 patients older than 18 years were invited to participate in the study. Disability, as evaluated by functional independence measurement and Barthel incapacitation score, Hamilton Rating Scale for Depression, and World Health Organization Quality of Life questionnaire (WHOQOL-BREF, was determined at baseline and after 3 and 6 months of treatment. Twenty-six patients agreed to participate in the study. All were treated because OT prevents blinding of a control group. Fifteen sessions of rehabilitative OT were applied over a period of 6 months. Difficult access to food, clothing, personal hygiene, and leisure were some of the main disabilities focused by these patients. After this treatment, disability scores and quality of life were stable, and the Hamilton scores for depression improved. Since no medication was started up to 6 months before or during OT, this improvement was related to our intervention. No association was found between these endpoints and a CAG tract of the MJD1 gene (CAGn, age, age of onset, or neurological scores at baseline (Spearman test. Although the possibly temporary stabilization of the downhill disabilities as an effect of OT remains to be established, its clear effect on depressive symptoms confirms the recommendation of OT to any patient with SCA3 or spinocerebellar ataxia.

  11. Yoga-based intervention in patients with somatoform disorders: an open label trial.

    Science.gov (United States)

    Sutar, Roshan; Desai, Geetha; Varambally, Shivarama; Gangadhar, B N

    2016-06-01

    Somatoform disorders are common mental disorders associated with impaired functioning and increased utilization of health resources. Yoga-based interventions have been used successfully for anxiety, depression, and chronic pain conditions. However, literature on the use of yoga in treatment of somatoform disorders is minimal. The current study assessed the effect of a specific yoga-based intervention in patients with somatoform disorders. Consenting patients meeting ICD-10 criteria for somatoform disorders were offered a specific yoga module (1 h per day) as a treatment. Assessments including Visual Analogue Scale (VAS), Brief Pain Inventory (BPI), and others were carried out at baseline and after 2, 6, and 12 weeks. Sixty-four subjects were included in the study and 34 completed 12 weeks follow-up. Significant improvement was noted in pain severity from baseline to 12 weeks after regular yoga sessions. The mean VAS score dropped from 7.24 to 2.88. Worst and average pain score in the last 24 h on BPI dropped from 7.71 to 3.26 and from 6.12 to 2.0,7 respectively. Results of the study suggest that yoga-based intervention can be one of the non-pharmacological treatment options in somatoform disorders. These preliminary findings need replication in larger controlled studies. PMID:27286363

  12. Open Label Trial of Naltrexone Implants: Measuring Blood Serum Levels of Naltrexone

    OpenAIRE

    Ross M. Colquhoun

    2013-01-01

    The usefulness of oral naltrexone has been limited by compliance. Sub-cutaneous implants would seem to offer a solution to this problem and improve long-term outcomes. The aim of the present study was to compare levels of blood serum naltrexone of patients who had received a naltrexone implant after detoxification to a number of dependent variables of interest. These dependent variables included drug use including urine screens of each patient, any adverse response to the implant, subjective ...

  13. Risperidone in Children and Adolescents with Conduct Disorder: A Single-Center, Open-Label Study

    OpenAIRE

    Ercan, Eyüp Sabri; Kutlu, Ayşe; Çıkoğlu, Sibel; Veznedaroğlu, Baybars; Erermiş, Serpil; Varan, Azmi

    2003-01-01

    Background: Risperidone is one of the most commonly used atypical antipsychotic drugs in the treatment of children and adolescents. However, the data about its use in children and adolescents with conduct disorder (CD) are limited.

  14. Open-Label, Long-Term Safety Study of Cevimeline in the Treatment of Postirradiation Xerostomia

    International Nuclear Information System (INIS)

    Purpose: To assess the safety of long-term cevimeline treatment of radiation-induced xerostomia in patients with head-and-neck cancer; and to assess the efficacy of cevimeline in these patients. Methods and Materials: A total of 255 adults with head-and-neck cancer who had received more than 40 Gy of radiation 4 months or more before entry and had clinically significant salivary gland dysfunction received cevimeline hydrochloride 45 mg t.i.d. orally for 52 weeks. Adverse events (AEs), their severity, and their relationship to the study medication were assessed by each investigator. The efficacy assessment was based on subjects' global evaluation of oral dryness on a scale of 0 (none) to 3 (severe). Results: Overall, 175 subjects (68.6%) experienced expected treatment-related AEs, most mild to moderate. The most frequent was increased sweating (47.5%), followed by dyspepsia (9.4%), nausea (8.2%), and diarrhea (6.3%). Fifteen subjects (5.9%) experienced Grade 3 treatment-related AEs, of which the most frequent was increased sweating. Eighteen subjects (7.1%) reported at least one serious AE, and 45 subjects (17.6%) discontinued study medication because of an AE. The global efficacy evaluation at the last study visit showed that cevimeline improved dry mouth in most subjects (59.2%). Significant improvement was seen at each study visit in the mean change from baseline of the numeric global evaluation score (p < 0.0001). Conclusions: Cevimeline 45 mg t.i.d. was generally well tolerated over a period of 52 weeks in subjects with xerostomia secondary to radiotherapy for cancer in the head-and-neck region

  15. Tazemetostat Rollover Study (TRuST): An Open-Label Rollover Study

    Science.gov (United States)

    2016-09-13

    Diffuse Large B-cell Lymphoma; Follicular Lymphoma; Malignant Rhabdoid Tumors (MRT); Rhabdoid Tumors of the Kidney (RTK); Atypical Teratoid Rhabdoid Tumors (ATRT); Synovial Sarcoma; Epitheliod Sarcoma; Mesothelioma; Advanced Solid Tumors

  16. Adjunctive agomelatine therapy in the treatment of acute bipolar II depression: a preliminary open label study

    OpenAIRE

    Fornaro M; McCarthy MJ; De Berardis D; De Pasquale C; Tabaton M; Martino M; Colicchio S; Cattaneo CI; D'Angelo E; Fornaro P

    2013-01-01

    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 Trea...

  17. Trazodone for the treatment of fibromyalgia: an open-label, 12-week study

    Directory of Open Access Journals (Sweden)

    Morillas-Arques Piedad

    2010-09-01

    Full Text Available Abstract Background Despite its frequent use as a hypnotic, trazodone has not been systematically assessed in fibromyalgia patients. In the present study have we evaluated the potential effectiveness and tolerability of trazodone in the treatment of fibromyalgia. Methods A flexible dose of trazodone (50-300 mg/day, was administered to 66 fibromyalgia patients for 12 weeks. The primary outcome measure was the Pittsburgh Sleep Quality Index (PSQI. Secondary outcome measures included the Fibromyalgia Impact Questionnaire (FIQ, the Beck Depression Inventory (BDI, the Hospital Anxiety and Depression Scale (HADS, the Brief Pain Inventory (BPI, the Short-Form Health Survey (SF-36, and the Patients' Global Improvement Scale (PGI. Trazodone's emergent adverse reactions were recorded. Data were analyzed with repeated measures one-way ANOVA and paired Student's t test. Results Trazodone markedly improved sleep quality, with large effect sizes in total PSQI score as well on sleep quality, sleep duration and sleep efficiency. Significant improvement, although with moderate effect sizes, were also observed in total FIQ scores, anxiety and depression scores (both HADS and BDI, and pain interference with daily activities. Unexpectedly, the most frequent and severe side effect associated with trazodone in our sample was tachycardia, which was reported by 14 (21.2% patients. Conclusions In doses higher than those usually prescribed as hypnotic, the utility of trazodone in fibromyalgia management surpasses its hypnotic activity. However, the emergence of tachycardia should be closely monitored. Trial registration This trial has been registered with ClinicalTrials.gov number NCT-00791739.

  18. Safety and effectiveness of divalproex sodium extended release containing regimen in Indian patients with bipolar I disorder in continuation phase: Results of EASED registry.

    Science.gov (United States)

    Shah, Nilesh; Reddy, M S; Vohra, Sandeep; Chaudhuri, Uday; Mohanasundaram, Senthilnathan

    2016-04-01

    The study was conducted to evaluate the safety and effectiveness of divalproex sodium XR containing regimen in patients with bipolar disorder (BPD) who are in continuation phase. It was an open-label, prospective, observational study conducted from July 2010 to December 2011 at 48 sites across India. Adult patients with bipolar I disorder of manic or mixed type fulfilling the DSM-IV criteria and who were in the continuation phase were included. Safety (primary outcome) was assessed by incidence of treatment emergent adverse events (AEs). Effectiveness (secondary outcome), was evaluated by proportion of patients who did not have a relapse, change in Clinical Global Impression Score-BP version-Severity of Illness (CGI-BP) and Young's Mania Rating Scale (YMRS) score. Data was recorded at three visits: visit-1 (baseline), visit-2 (end of 2 months ± 7 days) and visit-3 (end of 4 months ± 14 days), and summarised using descriptive statistics. pYMRS and CGI-BP scores from baseline to visit-3. Our study confirms the results of earlier studies in terms of good tolerability and effectiveness of divalproex sodium XR containing regimen in this study population. PMID:27025469

  19. Phase I trial of oral etoposide in combination with radiotherapy in head and neck squamous cell carcinoma - GORTEC 2004–02

    International Nuclear Information System (INIS)

    This study sought to determine the maximum tolerated dose (MTD) of oral etoposide in combination with radiotherapy in head and neck squamous cell carcinoma (HNSCC). Phase I, multicenter, open-labelled, non-comparative and dose escalating trial. Patients with locally advanced HNSCC were enrolled onto cohorts of escalating dose of etoposide. Oral etoposide was administered on five consecutive days every week for 7 weeks (7 treatment cycles) in combination with daily radiotherapy (70 Gy /35 fractions). Two dose levels (25 mg/day and 50 mg/day) of etoposide were planned and three to six patients were to be enrolled at each level according to the potential DLTs. Fourteen patients were allocated to two dose levels: 25 mg/day (3) and 50 mg/day (11). Cisplatin was contra-indicated in all the patients included. Only one patient (50 mg/day) presents a grade 4 neutropenia (DLT), no other DLTs were observed. The most frequently adverse events (AEs) were radiomucositis. Two deaths before 3 months of end of treatment were not related to treatment. Seven patients were still alive with a median follow-up of 30 months (12–58 months). Nine patients had a complete response (CR) at 3 months after the radiotherapy; Among the 9 patients, 3 patients had a local relapse; one patient with local and distant relapse. Due to only one DLT experienced, it is possible to a dose of 50 mg/day for phase II studies, however this should be considered with caution

  20. Retreatment with rituximab based on a treatment-to-target approach provides better disease control than treatment as needed in patients with rheumatoid arthritis: a retrospective pooled analysis

    Science.gov (United States)

    Mease, Philip J.; Rubbert-Roth, Andrea; Curtis, Jeffrey R.; Müller-Ladner, Ulf; Gaylis, Norman B.; Williams, Sarah; Reynard, Mark; Tyrrell, Helen

    2011-01-01

    Objective. To assess the efficacy and safety profiles of two different rituximab retreatment regimens in patients with RA. Methods. Four hundred and ninety-three RA patients with an inadequate response to MTX recruited into rituximab Phase II/III studies received further courses of open-label rituximab based on two approaches: (i) treatment to target (TT): patients assessed 24 weeks after each course and retreated if not in remission [DAS in 28 joints based on ESR (DAS-28-ESR) ≥ 2.6]; (ii) treatment as needed (PRN): patients retreated at the physician’s discretion ≥24 weeks following the first course and ≥16 weeks following further courses, if both swollen and tender joint counts were ≥8. All courses consisted of i.v. rituximab 2 × 1000 mg 2 weeks apart plus MTX. Observed data were analysed according to treatment strategy. Results. Multiple courses of rituximab maintained or improved responses irrespective of regimen. TT provided tighter control of disease activity with significantly greater improvements in DAS-28-ESR and lower HAQ-disability index scores vs PRN. TT resulted in significantly more patients achieving major clinical response. PRN resulted in recurrence of disease symptoms between courses, with TT significantly reducing the incidence of RA flares. Despite more frequent retreatment with TT compared with PRN, the rates of serious adverse events and serious infections were comparable between regimens. Conclusions. Retreatment with rituximab based on 24-week evaluations and to a target of DAS-28-ESR remission leads to improved efficacy and tighter control of disease activity compared with PRN without a compromised safety profile. TT may be the preferable rituximab treatment regimen for patients with RA. PMID:21926153

  1. Phase II Trials of Erlotinib or Gefitinib in Patients with Recurrent Meningioma

    Science.gov (United States)

    Norden, Andrew D.; Raizer, Jeffrey J.; Abrey, Lauren E.; Lamborn, Kathleen R.; Lassman, Andrew B.; Chang, Susan M.; Yung, W.K. Alfred; Gilbert, Mark R.; Fine, Howard A.; Mehta, Minesh; DeAngelis, Lisa M.; Cloughesy, Timothy F.; Robins, H. Ian; Aldape, Kenneth; Dancey, Janet; Prados, Michael D.; Lieberman, Frank; Wen, Patrick Y.

    2013-01-01

    There are no established treatments for recurrent meningioma when surgical and radiation options are exhausted. The epidermal growth factor receptor (EGFR) is often over-expressed in meningiomas and may promote tumor growth. In open label, single arm phase II studies of the EGFR inhibitors gefitinib (NABTC 00-01) and erlotinib (NABTC 01-03) for recurrent malignant gliomas, we included exploratory subsets of recurrent meningioma patients. We have pooled the data and report the results here. Patients with recurrent histologically confirmed meningiomas with no more than 2 previous chemotherapy regimens were treated with gefitinib 500 mg/day or erlotinib 150 mg/day until tumor progression or unacceptable toxicity. Twenty-five eligible patients were enrolled with median age 57 years (range 29–81) and median Karnofsky performance status (KPS) score 90 (range 60–100). Sixteen patients (64%) received gefitinib and 9 (36%) erlotinib. Eight patients (32%) had benign tumors, 9 (36%) atypical, and 8 (32%) malignant. For benign tumors, the 6-month progression-free survival (PFS6) was 25%, 12-month PFS (PFS12) 13%, 6-month overall survival (OS6) 63%, and 12-month OS (OS12) 50%. For atypical and malignant tumors, PFS6 was 29%, PFS12 18%, OS6 71%, and OS12 65%. The PFS and OS were not significantly different by histology. There were no objective imaging responses, but 8 patients (32%) maintained stable disease. Although treatment was well-tolerated, neither gefitinib nor erlotinib appear to have significant activity against recurrent meningioma. The role of EGFR inhibitors in meningiomas is unclear. Evaluation of multi-targeted inhibitors and EGFR inhibitors in combination with other targeted molecular agents may be warranted. PMID:19562255

  2. Skeletal improvement in patients with Gaucher disease type 1: a phase 2 trial of oral eliglustat

    Energy Technology Data Exchange (ETDEWEB)

    Kamath, Ravi S. [Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Fairfax Radiological Consultants, Fairfax, VA (United States); Lukina, Elena [Russian Academy of Medical Sciences, Moscow (Russian Federation); Watman, Nora [Hospital Ramos Mejia, Buenos Aires (Argentina); Dragosky, Marta [Instituto Mexicano del Seguro Social Hospital de Especialidades, Col. La Raza (Mexico); Pastores, Gregory M. [New York University, New York (United States); Yale University School of Medicine, New Haven, CT (United States); Arreguin, Elsa Avila [Instituto Argentino de Diagnostico y Tratamiento, Buenos Aires (Argentina); Rosenbaum, Hanna [Rambam Medical Center, Haifa (Israel); Zimran, Ari [Sha' are Zedek Hebrew University and Hadassah Medical School, Jerusalem (Israel); Aguzzi, Rasha [Genzyme, a Sanofi company, Cambridge, MA (United States); Alexion Pharmaceuticals, Cambridge, MA (United States); Puga, Ana Cristina; Norfleet, Andrea M.; Peterschmitt, M.J. [Genzyme, a Sanofi company, Cambridge, MA (United States); Rosenthal, Daniel I. [Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Massachusetts General Hospital, Department of Radiology, Boston, MA (United States)

    2014-10-15

    Eliglustat is an investigational oral substrate reduction therapy for Gaucher disease type 1 (GD1). Its skeletal effects were evaluated by prospective monitoring of bone mineral density (BMD), fractures, marrow infiltration by Gaucher cells, focal bone lesions, and infarcts during an open-label, multi-site, single-arm phase 2 trial (NCT00358150). Institutional review board approval and patient informed consent were obtained. Eliglustat (50 or 100 mg) was self-administered by mouth twice daily; 19 patients completed 4 years of treatment. All were skeletally mature (age range, 18-55 years). DXA and MRI assessments were conducted at baseline and annually thereafter. X-rays were obtained annually until month 24, and then every other year. Lumbar spine BMD increased significantly (p = 0.02; n = 15) by a mean (SD) of 9.9 % (14.2 %) from baseline to year 4; corresponding T-scores increased significantly (p = 0.01) from a mean (SD) of -1.6 (1.1) to -0.9 (1.3). Mean femur T-score remained normal through 4 years. Femur MRI showed that 10/18 (56 %) patients had decreased Gaucher cell infiltration compared to baseline; one patient with early improvement had transient worsening at year 4. There were no lumbar spine or femoral fractures and no reported bone crises during the study. At baseline, 8/19 (42 %) patients had focal bone lesions, which remained stable, and 7/19 (37 %) patients had bone infarctions, which improved in one patient by year 2. At year 4, one new asymptomatic, indeterminate bone lesion was discovered that subsequently resolved. Eliglustat may be a therapeutic option for treating the skeletal manifestations of GD1. (orig.)

  3. Phase contrast image synthesis

    DEFF Research Database (Denmark)

    Glückstad, J.

    1996-01-01

    A new method is presented for synthesizing arbitrary intensity patterns based on phase contrast imaging. The concept is grounded on an extension of the Zernike phase contrast method into the domain of full range [0; 2 pi] phase modulation. By controlling the average value of the input phase...... function and by choosing appropriate phase retardation at the phase contrast filter, a pure phase to intensity imaging is accomplished. The method presented is also directly applicable in dark field image synthesis....

  4. FRAGMATIC: A randomised phase III clinical trial investigating the effect of fragmin® added to standard therapy in patients with lung cancer

    Directory of Open Access Journals (Sweden)

    Macbeth Fergus R

    2009-10-01

    Full Text Available Abstract Background Venous thromboembolism (VTE occurs when blood clots in the leg, pelvic or other deep vein (deep vein thrombosis with or without transport of the thrombus into the pulmonary arterial circulation (pulmonary embolus. VTE is common in patients with cancer and is increased by surgery, chemotherapy, radiotherapy and disease progression. Low molecular weight heparin (LMWH is routinely used to treat VTE and some evidence suggests that LMWH may also have an anticancer effect, by reduction in the incidence of metastases. The FRAGMATIC trial will assess the effect of adding dalteparin (FRAGMIN, a type of LMWH, to standard treatment for patients with lung cancer. Methods/Design The study design is a randomised multicentre phase III trial comparing standard treatment and standard treatment plus daily LMWH for 24 weeks in patients with lung cancer. Patients eligible for this study must have histopathological or cytological diagnosis of primary bronchial carcinoma (small cell or non-small cell within 6 weeks of randomisation, be 18 or older, and must be willing and able to self-administer 5000 IU dalteparin by daily subcutaneous injection or have it administered to themselves or by a carer for 24 weeks. A total of 2200 patients will be recruited from all over the UK over a 3 year period and followed up for a minimum of 1 year after randomisation. Patients will be randomised to one of the two treatment groups in a 1:1 ratio, standard treatment or standard treatment plus dalteparin. The primary outcome measure of the trial is overall survival. The secondary outcome measures include venous thrombotic event (VTE free survival, serious adverse events (SAEs, metastasis-free survival, toxicity, quality of life (QoL, levels of breathlessness, anxiety and depression, cost effectiveness and cost utility. Trial registration Current Controlled Trials ISRCTN80812769

  5. Immunomodulatory effects in a phase II study of lenalidomide combined with cetuximab in refractory KRAS-mutant metastatic colorectal cancer patients.

    Directory of Open Access Journals (Sweden)

    Anita K Gandhi

    Full Text Available This study assessed the immunomodulatory effects in previously treated KRAS-mutant metastatic colorectal cancer patients participating in a phase II multicenter, open-label clinical trial receiving lenalidomide alone or lenalidomide plus cetuximab. The main findings show the T cell immunostimulatory properties of lenalidomide as the drug induced a decrease in the percentage CD45RA(+ naïve T cells 3-fold while increasing the percentage HLA-DR(+ activated T helper cells and percentage total CD45RO(+ CD8(+ memory T cytotoxic cells, 2.6- and 2.1-fold respectively (p<0.0001. In addition, lenalidomide decreased the percentage of circulating CD19(+ B cells 2.6-fold (p<0.0001. Lenalidomide increased a modest, yet significant, 1.4-fold change in the percentage of circulating natural killer cells. Our findings indicate that lenalidomide significantly activates T cells, suggestive of an immunotherapeutic role for this drug in settings of maintenance therapy and tumor immunity. Furthermore, reported for the first time is the effect of lenalidomide in combination with cetuximab on T cell function, including increases in circulating naïve and central memory T cells. In summary, lenalidomide and cetuximab have significant effects on circulating immune cells in patients with colorectal carcinoma.ClinicalTrials.gov NCT01032291.

  6. A phase II trial of the BCL-2 homolog domain 3 mimetic AT-101 in combination with docetaxel for recurrent, locally advanced, or metastatic head and neck cancer

    Science.gov (United States)

    Swiecicki, Paul L.; Bellile, Emily; Sacco, Assuntina G.; Pearson, Alexander T.; Taylor, Jeremy M. G.; Jackson, Trachette L.; Chepeha, Douglas B.; Spector, Matthew E.; Shuman, Andrew; Malloy, Kelly; Moyer, Jeffrey; McKean, Erin; McLean, Scott; Sukari, Ammar; Wolf, Gregory T.; Eisbruch, Avraham; Prince, Mark; Bradford, Carol; Carey, Thomas E.; Wang, Shaomeng; Nör, Jacques E.; Worden, Francis P.

    2016-01-01

    Background AT-101 is a BCL-2 Homolog domain 3 mimetic previously demonstrated to have tumoricidal effects in advanced solid organ malignancies. Given the evidence of activity in xenograft models, treatment with AT-101 in combination with docetaxel is a therapeutic doublet of interest in metastatic head and neck squamous cell carcinoma. Patients and Methods Patients included in this trial had unresectable, recurrent, or distantly metastatic head and neck squamous cell carcinoma (R/M HNSCC) not amenable to curative radiation or surgery. This was an open label randomized, phase II trial in which patients were administered AT-101 in addition to docetaxel. The three treatment arms were docetaxel, docetaxel plus pulse dose AT-101, and docetaxel plus metronomic dose AT-101. The primary endpoint of this trial was overall response rate. Results Thirty-five patients were registered and 32 were evaluable for treatment response. Doublet therapy with AT-101 and docetaxel was well tolerated with only 2 patients discontinuing therapy due to treatment related toxicities. The overall response rate was 11% (4 partial responses) with a clinical benefit rate of 74%. Median progression free survival was 4.3 months (range: 0.7–13.7) and overall survival was 5.5 months (range: 0.4–24). No significant differences were noted between dosing strategies. Conclusion Although met with a favorable toxicity profile, the addition of AT-101 to docetaxel in R/M HNSCC does not appear to demonstrate evidence of efficacy. PMID:27225873

  7. Phase II Study of Biweekly Plitidepsin as Second-Line Therapy for Advanced or Metastatic Transitional Cell Carcinoma of the Urothelium

    Directory of Open Access Journals (Sweden)

    Sergio Szyldergemajn

    2009-09-01

    Full Text Available The objective of this exploratory, open-label, single-arm, phase II clinical trial was to evaluate plitidepsin (5 mg/m2 administered as a 3-hour continuous intravenous infusion every two weeks to patients with locally advanced/metastatic transitional cell carcinoma of the urothelium who relapsed/progressed after first-line chemotherapy. Treatment cycles were repeated for up to 12 cycles or until disease progression, unacceptable toxicity, patient refusal or treatment delay for >2 weeks. The primary efficacy endpoint was objective response rate according to RECIST. Secondary endpoints were the rate of SD lasting ≥6 months and time-to-event variables. Toxicity was assessed using NCI-CTC v. 3.0. Twenty-one patients received 57 treatment cycles. No objective tumor responses occurred. SD lasting <6 months was observed in two of 18 evaluable patients. With a median follow-up of 4.6 months, the median PFR and the median OS were 1.4 months and 2.3 months, respectively. The most common AEs were mild to moderate nausea, fatigue, myalgia and anorexia. Anemia, lymphopenia, and increases in transaminases, alkaline phosphatase and creatinine were the most frequent laboratory abnormalities. No severe neutropenia occurred. Treatment was feasible and generally well tolerated in this patient population; however the lack of antitumor activity precludes further studies of plitidepsin in this setting.

  8. Effective elimination of dabigatran by haemodialysis. A phase I single-centre study in patients with end-stage renal disease.

    Science.gov (United States)

    Khadzhynov, Dmytro; Wagner, Frank; Formella, Stephan; Wiegert, Erol; Moschetti, Viktoria; Slowinski, Torsten; Neumayer, Hans-H; Liesenfeld, Karl-Heinz; Lehr, Thorsten; Härtter, Sebastian; Friedman, Jeffrey; Peters, Harm; Clemens, Andreas

    2013-04-01

    Dabigatran, a specific, reversible direct thrombin inhibitor, is used to prevent ischaemic and haemorrhagic strokes in patients with atrial fibrillation. As with every anticoagulant, there is a need to rapidly reverse its effects in emergency situations. In an open-label, single-centre phase I study with two fixed multiple dosing periods, we investigated the pharmacokinetics, pharmacodynamics and safety of dabigatran before, during and after 4 hour haemodialysis sessions with either 200 or 400 ml/min targeted blood flow in seven end-stage renal disease patients without atrial fibrillation. Dabigatran was administered over three days in a regimen designed to achieve peak plasma concentrations comparable to those observed in atrial fibrillation patients receiving 150 mg b.i.d. and to attain adequate distribution of dabigatran in the central and peripheral compartments. Plasma concentration-time profiles were similar in both periods on Day 3 (Cmax: 176 and 159 ng/ml). Four hours of haemodialysis removed 48.8% and 59.3% of total dabigatran from the central compartment with 200 and 400 ml/minute targeted blood flow, respectively. The anticoagulant activity of dabigatran was linearly related to its plasma levels. There was a minor redistribution of dabigatran (anticoagulant activity. There was a clinically negligible redistribution of dabigatran after haemodialysis. These results demonstrate that haemodialysis can be a suitable approach to eliminate dabigatran in emergency situations. PMID:23389759

  9. Stage I of Phase II study assessing efficacy, safety and tolerability of barasertib (AZD1152) versus LDAC in elderly AML patients

    Science.gov (United States)

    Kantarjian, Hagop M; Martinelli, Giovanni; Jabbour, Elias J; Quintás-Cardama, Alfonso; Ando, Kiyoshi; Bay, Jacques-Olivier; Wei, Andrew; Gröpper, Stefanie; Papayannidis, Cristina; Owen, Kate; Pike, Laura; Schmitt, Nicola; Stockman, Paul K; Giagounidis, Aristoteles

    2013-01-01

    Background This Phase II study evaluated the efficacy, safety and tolerability of the Aurora B kinase inhibitor barasertib, compared with low-dose cytosine arabinoside (LDAC), in patients aged ≥60 years with acute myeloid leukemia (AML). Methods Patients were randomized 2:1 to open-label barasertib 1200 mg (7-day iv infusion) or LDAC 20 mg (sc twice-daily for 10 days) in 28-day cycles. The primary endpoint was objective complete response rate (OCRR: CR + CRi [Cheson criteria, additionally requiring CRi reconfirmation ≥21 days after first appearance and associated with partial recovery of platelets and neutrophils]). Secondary endpoints included overall survival (OS) and safety. Results 74 patients (barasertib, n=48; LDAC, n=26) completed ≥1 cycle. A significant improvement in OCRR was observed with barasertib (35.4% vs 11.5%; difference, 23.9% [95% CI, 2.7–39.9]; P<0.05). Although not formally sized to compare OS data, the median OS with barasertib was 8.2 months versus 4.5 months with LDAC. (HR=0.88, 95% CI, 0.49-1.58; P=0.663;). Stomatitis and febrile neutropenia were the most common adverse events with barasertib versus LDAC (71% vs 15%; 67% vs 19%, respectively). Conclusions Barasertib showed a significant improvement in OCRR versus LDAC, with a more toxic but manageable safety profile that was consistent with previous studies. Clinicaltrials.gov, NCT00952588. PMID:23605952

  10. Phase I Trial Using Proteasome Inhibitor Bortezomib and Concurrent Temozolomide and Radiotherapy for Central Nervous System Malignancies

    International Nuclear Information System (INIS)

    Purpose: To evaluate the toxicity and response rate of bortezomib with concurrent radiotherapy and temozolomide in the treatment of patients with central nervous system malignancies. Patients and Methods: This open-label, dose-escalation, Phase I clinical study evaluated the safety of three dose levels of intravenously administered bortezomib (0.7, 1.0, and 1.3 mg/m2/dose) on Days 1, 4, 8, and 11 of a 21-day cycle, in addition to concurrent radiotherapy and temozolomide at a daily dose of 75 mg/m2 starting on Day 1. The primary endpoint was dose-limiting toxicity, defined as any Grade 4-5 toxicity or Grade 3 toxicity directly attributable to protocol treatment, requiring hospitalization and/or radiotherapy interruption. The secondary endpoints included feasibility, non-dose-limiting toxicity, and treatment response. Results: A total of 27 patients were enrolled, 23 of whom had high-grade glioma (10 recurrent and 13 newly diagnosed). No dose-limiting toxicities were noted in any dose group, including the highest (1.3 mg/m2/dose). The most frequent toxicities were Grade 1 and 2 stomatitis, erythema, and alopecia. All 27 patients were evaluable for response. At a median follow-up of 15.0 months, 9 patients were still alive, with a median survival of 17.4 months for all patients and 15.0 months for patients with high-grade glioma. Conclusion: Bortezomib administered at its typical 'systemic' dose (1.3 mg/m2) is well tolerated and safe combined with temozolomide and radiotherapy when used in the treatment of central nervous system malignancies. A Phase II study to characterize efficacy is warranted.

  11. Phase 2a study of ataluren-mediated dystrophin production in patients with nonsense mutation Duchenne muscular dystrophy.

    Directory of Open Access Journals (Sweden)

    Richard S Finkel

    Full Text Available BACKGROUND: Approximately 13% of boys with Duchenne muscular dystrophy (DMD have a nonsense mutation in the dystrophin gene, resulting in a premature stop codon in the corresponding mRNA and failure to generate a functional protein. Ataluren (PTC124 enables ribosomal readthrough of premature stop codons, leading to production of full-length, functional proteins. METHODS: This Phase 2a open-label, sequential dose-ranging trial recruited 38 boys with nonsense mutation DMD. The first cohort (n = 6 received ataluren three times per day at morning, midday, and evening doses of 4, 4, and 8 mg/kg; the second cohort (n = 20 was dosed at 10, 10, 20 mg/kg; and the third cohort (n = 12 was dosed at 20, 20, 40 mg/kg. Treatment duration was 28 days. Change in full-length dystrophin expression, as assessed by immunostaining in pre- and post-treatment muscle biopsy specimens, was the primary endpoint. FINDINGS: Twenty three of 38 (61% subjects demonstrated increases in post-treatment dystrophin expression in a quantitative analysis assessing the ratio of dystrophin/spectrin. A qualitative analysis also showed positive changes in dystrophin expression. Expression was not associated with nonsense mutation type or exon location. Ataluren trough plasma concentrations active in the mdx mouse model were consistently achieved at the mid- and high- dose levels in participants. Ataluren was generally well tolerated. INTERPRETATION: Ataluren showed activity and safety in this short-term study, supporting evaluation of ataluren 10, 10, 20 mg/kg and 20, 20, 40 mg/kg in a Phase 2b, double-blind, long-term study in nonsense mutation DMD. TRIAL REGISTRATION: ClinicalTrials.gov NCT00264888.

  12. Phase locked loop

    OpenAIRE

    Beek, van, P.; Klumperink, Eric Antonius Maria; Nauta, Bram; Vaucher, Cicero Silveira

    2007-01-01

    A phase locked loop comprising a phase detector ( 100 ) for determining a phase difference between a reference signal (Ref) and mutually phase shifted signals (I, Q) to generate frequency control signals (U, D), the phase detector ( 100 ) comprising: means ( 10 ) for obtaining a first one of said frequency control signals (U, D) by binary multiplication of the reference signal (Ref) and one of the relative phase shifted signals (I, Q); and means ( 20 ) for obtaining a second one of said frequ...

  13. Phase equilibrium engineering

    CERN Document Server

    Brignole, Esteban Alberto

    2013-01-01

    Traditionally, the teaching of phase equilibria emphasizes the relationships between the thermodynamic variables of each phase in equilibrium rather than its engineering applications. This book changes the focus from the use of thermodynamics relationships to compute phase equilibria to the design and control of the phase conditions that a process needs. Phase Equilibrium Engineering presents a systematic study and application of phase equilibrium tools to the development of chemical processes. The thermodynamic modeling of mixtures for process development, synthesis, simulation, design and

  14. Impact of treatment with bevacizumab beyond disease progression: a randomized phase II study of docetaxel with or without bevacizumab after platinum-based chemotherapy plus bevacizumab in patients with advanced nonsquamous non–small cell lung cancer (WJOG 5910L)

    International Nuclear Information System (INIS)

    Bevacizumab, a humanized antibody to vascular endothelial growth factor (VEGF), shows clinical activity against human cancer, with its addition to standard chemotherapy having been found to improve outcome in patients with advanced nonsquamous non–small cell lung cancer (NSCLC). However, there have been no evidence-based studies to support the continued use of bevacizumab beyond disease progression in such patients treated with the drug in first-line therapy. We have now designed a randomized phase II trial to examine the clinical benefit and safety of continued bevacizumab treatment in patients with advanced nonsquamous NSCLC whose disease has progressed after first-line treatment with bevacizumab plus a platinum-based doublet. WJOG 5910L was designed as a multicenter, open-label, randomized, phase II trial by the West Japan Oncology Group of docetaxel (arm A) versus docetaxel plus bevacizumab (arm B) in patients with recurrent or metatstatic nonsquamous NSCLC whose disease has progressed after first-line treatment with bevacizumab plus a platinum-based doublet. Patients in arm A will receive docetaxel at 60 mg/m2 and those in arm B will receive docetaxel at 60 mg/m2 plus bevacizumab at 15 mg/kg, with each drug administered on day 1 every 21 days until progression or unacceptable toxicity. The primary endpoint of the study is progression-free survival, with secondary endpoints including response rate, overall survival, and safety, for patients treated in either arm. UMIN (University Hospital Medical Information Network in Japan) 000004715

  15. A brief cognitive-behavioural intervention for treating depression and panic disorder in patients with noncardiac chest pain: a 24-week randomized controlled trial

    NARCIS (Netherlands)

    M.H.C.T. van Beek; R.C. Oude Voshaar; A.M. Beek; G.A. van Zijderveld; S. Visser; A.E.M. Speckens; N. Batelaan; A.J.L.M. van Balkom

    2013-01-01

    Background: Most patients with noncardiac chest pain experience anxiety and depressive symptoms. Commonly they are reassured and referred back to primary care, leaving them undiagnosed and untreated. Some small studies have suggested efficacy of 12 cognitive behavioral therapy (CBT) sessions. Our ai

  16. Pegylated interferon alfa and ribavirin for 14 versus 24 weeks in patients with hepatitis C virus genotype 2 or 3 and rapid virological response

    DEFF Research Database (Denmark)

    Dalgard, Olav; Bjøro, Kristian; Larsen, Helmer Ring;

    2008-01-01

    treatment-naïve HCV RNA-positive patients with genotype 2 or 3 were enrolled. Patients with RVR were randomized to 14 (group A) or 24 (group B) weeks of treatment. Patients were treated with pegylated interferon alpha-2b (1.5 microg/kg) subcutaneously weekly and ribavirin (800-1400 mg) orally daily...

  17. Effects of a 24-week course of interferon-α therapy after curative treatment of hepatitis C virus-associated hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To assess whether a 24-wk course of interferon (IFN) could prevent hepatocellular carcinoma (HCC) recurrence and worsening of liver function in patients with hepatitis C virus (HCV)-infected patients after receiving curative treatment for primary HCC. METHODS: Outcomes in 42 patients with HCV infection treated with IFN-α, after curative treatment for primary HCC (IFN group), were compared with 42 matched curatively treated historical controls not given IFN (nonIFN group). RESULTS: Although the rate of initial recurrence did not differ significantly between IFN group and non-IFN group (0%, 44%, 61%, and 67% vs 4.8%, 53%, 81%, and 87% at 1, 3, 5, and 7 years, P = 0.153, respectively), IFN group showed a lower rate than the non-IFN group for second recurrence (0%, 10.4%, 28%, and 35% vs 0%, 30%, 59%, and 66% at 1, 3, 5 and 7 years, P = 0.022, respectively). Among the IFN group, patients with sustained virologic response (SVR) were less likely to have a second HCC recurrence than IFN patients without an SVR, or non-IFN patients. Multivariate analysis identified the lack of SVR as the only independent risk factor for a second recurrence, while SVR and Child-Pugh class A independently favored overall survival. CONCLUSION: Most intrahepatic recurrences of HCVrelated HCC occurred during persistent viral infection. Eradication of HCV is essential for the prevention of HCC recurrence and improvement of survival.

  18. PTH(1-84) Replacement Therapy in Hypoparathyroidism (HypoPT): a Randomized Controlled Trial on Pharmacokinetics and Dynamic effects Following 24 Weeks of treatment

    DEFF Research Database (Denmark)

    Sikjær, Tanja Tvistholm; Amstrup, Anne Kristine; Rolighed, Lars;

    in the diurnal rhythms of plasma ionized calcium and 1,25(OH)2D levels (Figure), with rising levels reaching a peak app. 8h following the injection. 4 to 12h following injection, asymptomatic hypercalcemia (>1.32 mmol/l) was present in 41% of PTH treated patients. Despite hypercalcemia, renal excretion...... or similar placebo, as add to conventional therapy. At end of study, we performed a 24h biochemical monitoring on 39 patients (22 on PTH) in order to assess effects on diurnal variations in calcium-phosphate homeostasis. Following injection, blood samples were obtained at 0.25, 0.5, 1.0, 1.5, 2, 3, 4, 5, 6......, 7, 8, 10, 12, 16, 20, 24h and urine was collected for the time intervals: 0-2, 2-4, 4-8, 8-16, and 16-24h. Overall, during the 24-wks of therapy patients on PTH reduced their daily dose of calcium and active vitamin D significantly by 75% and 73%, respectively. Plasma PTH levels rose immediately...

  19. CrowdPhase: crowdsourcing the phase problem

    Energy Technology Data Exchange (ETDEWEB)

    Jorda, Julien; Sawaya, Michael R. [Institute for Genomics and Proteomics, 611 Charles Young Drive East, Los Angeles, CA 90095 (United States); Yeates, Todd O., E-mail: yeates@mbi.ucla.edu [Institute for Genomics and Proteomics, 611 Charles Young Drive East, Los Angeles, CA 90095 (United States); Molecular Biology Institute, 611 Charles Young Drive East, Los Angeles, CA 90095 (United States); University of California, 611 Charles Young Drive East, Los Angeles, CA 90095 (United States)

    2014-06-01

    The idea of attacking the phase problem by crowdsourcing is introduced. Using an interactive, multi-player, web-based system, participants work simultaneously to select phase sets that correspond to better electron-density maps in order to solve low-resolution phasing problems. The human mind innately excels at some complex tasks that are difficult to solve using computers alone. For complex problems amenable to parallelization, strategies can be developed to exploit human intelligence in a collective form: such approaches are sometimes referred to as ‘crowdsourcing’. Here, a first attempt at a crowdsourced approach for low-resolution ab initio phasing in macromolecular crystallography is proposed. A collaborative online game named CrowdPhase was designed, which relies on a human-powered genetic algorithm, where players control the selection mechanism during the evolutionary process. The algorithm starts from a population of ‘individuals’, each with a random genetic makeup, in this case a map prepared from a random set of phases, and tries to cause the population to evolve towards individuals with better phases based on Darwinian survival of the fittest. Players apply their pattern-recognition capabilities to evaluate the electron-density maps generated from these sets of phases and to select the fittest individuals. A user-friendly interface, a training stage and a competitive scoring system foster a network of well trained players who can guide the genetic algorithm towards better solutions from generation to generation via gameplay. CrowdPhase was applied to two synthetic low-resolution phasing puzzles and it was shown that players could successfully obtain phase sets in the 30° phase error range and corresponding molecular envelopes showing agreement with the low-resolution models. The successful preliminary studies suggest that with further development the crowdsourcing approach could fill a gap in current crystallographic methods by making it

  20. CrowdPhase: crowdsourcing the phase problem

    International Nuclear Information System (INIS)

    The idea of attacking the phase problem by crowdsourcing is introduced. Using an interactive, multi-player, web-based system, participants work simultaneously to select phase sets that correspond to better electron-density maps in order to solve low-resolution phasing problems. The human mind innately excels at some complex tasks that are difficult to solve using computers alone. For complex problems amenable to parallelization, strategies can be developed to exploit human intelligence in a collective form: such approaches are sometimes referred to as ‘crowdsourcing’. Here, a first attempt at a crowdsourced approach for low-resolution ab initio phasing in macromolecular crystallography is proposed. A collaborative online game named CrowdPhase was designed, which relies on a human-powered genetic algorithm, where players control the selection mechanism during the evolutionary process. The algorithm starts from a population of ‘individuals’, each with a random genetic makeup, in this case a map prepared from a random set of phases, and tries to cause the population to evolve towards individuals with better phases based on Darwinian survival of the fittest. Players apply their pattern-recognition capabilities to evaluate the electron-density maps generated from these sets of phases and to select the fittest individuals. A user-friendly interface, a training stage and a competitive scoring system foster a network of well trained players who can guide the genetic algorithm towards better solutions from generation to generation via gameplay. CrowdPhase was applied to two synthetic low-resolution phasing puzzles and it was shown that players could successfully obtain phase sets in the 30° phase error range and corresponding molecular envelopes showing agreement with the low-resolution models. The successful preliminary studies suggest that with further development the crowdsourcing approach could fill a gap in current crystallographic methods by making it

  1. INTERGRANULAR PHASES IN ELECTROCERAMICS

    OpenAIRE

    Metz, R; Brieu, M.; Legros, R.; Rousset, A.

    1990-01-01

    The stability of the resistivity of N.T.C. thermistors is improved by the presence of precipitated phases in the vicinity of the spinel phase. The electron microscopy study allows one to make sure that the barium does not enter the spinel spinel structure but rather the grains of spinel phase are coated with insulating phase. It can be suggested that the insulating phase could built-up diffusion barriers.

  2. Phase II and pharmacogenomics study of enzastaurin plus temozolomide during and following radiation therapy in patients with newly diagnosed glioblastoma multiforme and gliosarcoma.

    Science.gov (United States)

    Butowski, Nicholas; Chang, Susan M; Lamborn, Kathleen R; Polley, Mei-Yin; Pieper, Russell; Costello, Joseph F; Vandenberg, Scott; Parvataneni, Rupa; Nicole, Angelina; Sneed, Patricia K; Clarke, Jennifer; Hsieh, Emily; Costa, Bruno M; Reis, Rui M; Hristova-Kazmierski, Maria; Nicol, Steven J; Thornton, Donald E; Prados, Michael D

    2011-12-01

    This open-label, single-arm, phase II study combined enzastaurin with temozolomide plus radiation therapy (RT) to treat glioblastoma multiforme (GBM) and gliosarcoma. Adults with newly diagnosed disease and Karnofsky performance status (KPS) ≥ 60 were enrolled. Treatment was started within 5 weeks after surgical diagnosis. RT consisted of 60 Gy over 6 weeks. Temozolomide was given at 75 mg/m(2) daily during RT and then adjuvantly at 200 mg/m(2) daily for 5 days, followed by a 23-day break. Enzastaurin was given once daily during RT and in the adjuvant period at 250 mg/day. Cycles were 28 days. The primary end point was overall survival (OS). Progression-free survival (PFS), toxicity, and correlations between efficacy and molecular markers analyzed from tumor tissue samples were also evaluated. A prospectively planned analysis compared OS and PFS of the current trial with outcomes from 3 historical phase II trials that combined novel agents with temozolomide plus RT in patients with GBM or gliosarcoma. Sixty-six patients were enrolled. The treatment regimen was well tolerated. OS (median, 74 weeks) and PFS (median, 36 weeks) results from the current trial were comparable to those from a prior phase II study using erlotinib and were significantly better than those from 2 other previous studies that used thalidomide or cis-retinoic acid, all in combination with temozolomide plus RT. A positive correlation between O-6-methylguanine-DNA methyltransferase promoter methylation and OS was observed. Adjusting for age and KPS, no other biomarker was associated with survival outcome. Correlation of relevant biomarkers with OS may be useful in future trials.

  3. Pharmacokinetics, safety, and efficacy of APF530 (extended-release granisetron) in patients receiving moderately or highly emetogenic chemotherapy: results of two Phase II trials

    International Nuclear Information System (INIS)

    Despite advances with new therapies, a significant proportion of patients (>30%) suffer delayed-onset chemotherapy-induced nausea and vomiting (CINV) despite use of antiemetics. APF530 is a sustained-release subcutaneous (SC) formulation of granisetron for preventing CINV. APF530 pharmacokinetics, safety, and efficacy were studied in two open-label, single-dose Phase II trials (C2005-01 and C2007-01, respectively) in patients receiving moderately emetogenic chemotherapy or highly emetogenic chemotherapy. In C2005-01, 45 patients received APF530 250, 500, or 750 mg SC (granisetron 5, 10, or 15 mg, respectively). In C2007-01, 35 patients were randomized to APF530 250 or 500 mg SC. Injections were given 30 to 60 minutes before single-day moderately emetogenic chemotherapy or highly emetogenic chemotherapy. Plasma granisetron was measured from predose to 168 hours after study drug administration. Safety and efficacy were also evaluated. APF530 pharmacokinetics were dose proportional, with slow absorption and elimination of granisetron after a single SC dose. Median time to maximum plasma concentration and half-life were similar for APF530 250 and 500 mg in both trials, with no differences between the groups receiving moderately and highly emetogenic chemotherapy. Exposure to granisetron was maintained at a therapeutic level over the delayed-onset phase, at least 168 hours. Adverse events in both trials were as expected for granisetron; injection site reactions (eg, erythema and induration) were predominantly mild and seen in ≤20% of patients. Complete responses (no emesis, with no rescue medication) were obtained in the acute, delayed, and overall phases in ≥80% and ≥75% of patients in both trials with the 250 and 500 mg doses, respectively. After a single injection of APF530, there were dose-proportional pharmacokinetics and sustained concentrations of granisetron over 168 hours. The 250 and 500 mg doses were well tolerated and maintained therapeutic granisetron

  4. CrowdPhase: crowdsourcing the phase problem.

    Science.gov (United States)

    Jorda, Julien; Sawaya, Michael R; Yeates, Todd O

    2014-06-01

    The human mind innately excels at some complex tasks that are difficult to solve using computers alone. For complex problems amenable to parallelization, strategies can be developed to exploit human intelligence in a collective form: such approaches are sometimes referred to as `crowdsourcing'. Here, a first attempt at a crowdsourced approach for low-resolution ab initio phasing in macromolecular crystallography is proposed. A collaborative online game named CrowdPhase was designed, which relies on a human-powered genetic algorithm, where players control the selection mechanism during the evolutionary process. The algorithm starts from a population of `individuals', each with a random genetic makeup, in this case a map prepared from a random set of phases, and tries to cause the population to evolve towards individuals with better phases based on Darwinian survival of the fittest. Players apply their pattern-recognition capabilities to evaluate the electron-density maps generated from these sets of phases and to select the fittest individuals. A user-friendly interface, a training stage and a competitive scoring system foster a network of well trained players who can guide the genetic algorithm towards better solutions from generation to generation via gameplay. CrowdPhase was applied to two synthetic low-resolution phasing puzzles and it was shown that players could successfully obtain phase sets in the 30° phase error range and corresponding molecular envelopes showing agreement with the low-resolution models. The successful preliminary studies suggest that with further development the crowdsourcing approach could fill a gap in current crystallographic methods by making it possible to extract meaningful information in cases where limited resolution might otherwise prevent initial phasing. PMID:24914965

  5. Renal Sympathetic Denervation by CT-Guided Ethanol Injection: A Phase II Pilot Trial of a Novel Technique

    International Nuclear Information System (INIS)

    ObjectivesCT-guided ethanol-mediated renal sympathetic denervation in treatment of therapy-resistant hypertension was performed to assess patient safety and collect preliminary data on treatment efficacy.Materials and MethodsEleven patients with therapy-resistant hypertension (blood pressure of >160 mmHg despite three different antihypertensive drugs including a diuretic) and following screening for secondary causes were enrolled in a phase II single arm open label pilot trial of CT-guided neurolysis of sympathetic renal innervation. Primary endpoint was safety, and secondary endpoint was a decrease of the mean office as well as 24-h systolic blood pressure in follow-up. Follow-up visits at 4 weeks, 3, and 6 months included 24-h blood pressure assessments, office blood pressure, laboratory values, as well as full clinical and quality of life assessments.ResultsNo toxicities ≥3° occurred. Three patients exhibited worsened kidney function in follow-up analyses. When accounting all patients, office systolic blood pressure decreased significantly at all follow-up visits (maximal mean decrease −41.2 mmHg at 3 months). The mean 24-h systolic blood pressure values decreased significantly at 3 months, but not at 6 months (mean: −9.7 and −6.3 mmHg, respectively). Exclusion of five patients who had failed catheter-based endovascular denervation and/or were incompliant for antihypertensive drug intake revealed a more pronounced decrease of 24-h systolic blood pressure (mean: −18.3 and −15.2 mmHg at 3 and 6 months, p = 0.03 and 0.06).ConclusionCT-guided sympathetic denervation proved to be safe and applicable under various anatomical conditions with more renal arteries and such of small diameter

  6. Metronomic cyclophosphamide therapy in hormone-naive patients with non-metastatic biochemical recurrent prostate cancer: a phase II trial.

    Science.gov (United States)

    Calcagno, Fabien; Mouillet, Guillaume; Adotevi, Olivier; Maurina, Tristan; Nguyen, Thierry; Montcuquet, Philippe; Curtit, E; Kleinclauss, F; Pivot, Xavier; Borg, Christophe; Thiery-Vuillemin, Antoine

    2016-08-01

    After curative local therapy, biochemical recurrence is a mode of relapse among patient with prostate cancer (PC). Deferring androgen deprivation therapy (ADT) or offering non-hormonal therapies may be an appropriate option for these non-symptomatic patients with no proven metastases. Metronomic cyclophosphamide (MC) has shown activity in metastatic PC setting and was chosen to be assessed in biochemical relapse. This prospective single-arm open-label phase II study was conducted to evaluate MC regimen in patients with biochemical recurrent PC. MC was planned to be administered orally at a daily dose of 50 mg for 6 months. Primary endpoint was PSA response. Thirty-eight patients were included and treated. Median follow-up was 45.5 months (range 17-100). Among them, 14 patients (37 %) achieved PSA stabilisation and 22 patients (58 %) experienced PSA progression. Response rate was 5 % with one complete response (2.6 %), and 1 partial response with PSA decrease >50 % (2.6 %). The median time until androgen deprivation therapy initiation was around 15 months. The treatment was well tolerated. Neither grade 3-4 toxicity nor serious adverse events were observed. This first prospective clinical trial with MC therapy in patients with non-metastatic biochemical recurrence of PC displayed modest efficacy when measured with PSA response rate, without significant toxicity. It might offer a new safe and non-expensive option to delay initiation of ADT. These results would need to be confirmed with larger prospective randomised trials. PMID:27400698

  7. Examestane in advanced or recurrent endometrial carcinoma: a prospective phase II study by the Nordic Society of Gynecologic Oncology (NSGO)

    International Nuclear Information System (INIS)

    We evaluated the efficacy and safety of the aromatase inhibitor exemestane in patients with advanced, persistent or recurrent endometrial carcinoma. We performed an open-label one-arm, two-stage, phase II study of 25 mg of oral exemestane in 51 patients with advanced (FIGO stage III-IV) or relapsed endometrioid endometrial cancer. Patients were stratified into subsets of estrogen receptor (ER) positive and ER negative patients. Recruitment to the ER negative group was stopped prematurely after 12 patients due to slow accrual. In the ER positive patients, we observed an overall response rate of 10%, and a lack of progression after 6 months in 35% of the patients. No responses were registered in the ER negative patients, and all had progressive disease within 6 months. For the total group of patients, the median progression free survival (PFS) was 3.1 months (95% CI: 2.0-4.1). In the ER positive patients the median PFS was 3.8 months (95% CI: 0.7-6.9) and in the ER negative patients it was 2.6 months (95% CI: 2.1-3-1). In the ER positive patients the median overall survival (OS) time was 13.3 months (95% CI: 7.7-18.9), in the ER negative patients the corresponding numbers were 6.1 months (95% CI: 4.1-8.2). Treatment with exemestane was well tolerated. Treatment of estrogen positive advanced or recurrent endometrial cancer with exemestane, an aromatase inhibitor, resulted in a response rate of 10% and lack of progression after 6 months in 35% of the patients. Trial identification number (Clinical Trials.gov): http://www.clinicaltrials.gov/NCT01965080. Nordic Society of Gynecological Oncology: NSGO–EC–0302. EudraCT number: 2004-001103-35

  8. Renal Sympathetic Denervation by CT-Guided Ethanol Injection: A Phase II Pilot Trial of a Novel Technique

    Energy Technology Data Exchange (ETDEWEB)

    Ricke, J., E-mail: jens.ricke@med.ovgu.de; Seidensticker, M.; Becker, S. [Otto-von-Guericke University Magdeburg, Department of Radiology and Nuclear Medicine, Universitätsklinikum Magdeburg AöR (Germany); Schiefer, J. [Universitätsklinikum Magdeburg AöR, Department of Nephrology and Hypertension, Diabetes and Endocrinology (Germany); Adamchic, I.; Lohfink, K. [Otto-von-Guericke University Magdeburg, Department of Radiology and Nuclear Medicine, Universitätsklinikum Magdeburg AöR (Germany); Kandulski, M.; Heller, A.; Mertens, P. R. [Universitätsklinikum Magdeburg AöR, Department of Nephrology and Hypertension, Diabetes and Endocrinology (Germany)

    2016-02-15

    ObjectivesCT-guided ethanol-mediated renal sympathetic denervation in treatment of therapy-resistant hypertension was performed to assess patient safety and collect preliminary data on treatment efficacy.Materials and MethodsEleven patients with therapy-resistant hypertension (blood pressure of >160 mmHg despite three different antihypertensive drugs including a diuretic) and following screening for secondary causes were enrolled in a phase II single arm open label pilot trial of CT-guided neurolysis of sympathetic renal innervation. Primary endpoint was safety, and secondary endpoint was a decrease of the mean office as well as 24-h systolic blood pressure in follow-up. Follow-up visits at 4 weeks, 3, and 6 months included 24-h blood pressure assessments, office blood pressure, laboratory values, as well as full clinical and quality of life assessments.ResultsNo toxicities ≥3° occurred. Three patients exhibited worsened kidney function in follow-up analyses. When accounting all patients, office systolic blood pressure decreased significantly at all follow-up visits (maximal mean decrease −41.2 mmHg at 3 months). The mean 24-h systolic blood pressure values decreased significantly at 3 months, but not at 6 months (mean: −9.7 and −6.3 mmHg, respectively). Exclusion of five patients who had failed catheter-based endovascular denervation and/or were incompliant for antihypertensive drug intake revealed a more pronounced decrease of 24-h systolic blood pressure (mean: −18.3 and −15.2 mmHg at 3 and 6 months, p = 0.03 and 0.06).ConclusionCT-guided sympathetic denervation proved to be safe and applicable under various anatomical conditions with more renal arteries and such of small diameter.

  9. High temperature phase equilibria and phase diagrams

    CERN Document Server

    Kuo, Chu-Kun; Yan, Dong-Sheng

    2013-01-01

    High temperature phase equilibria studies play an increasingly important role in materials science and engineering. It is especially significant in the research into the properties of the material and the ways in which they can be improved. This is achieved by observing equilibrium and by examining the phase relationships at high temperature. The study of high temperature phase diagrams of nonmetallic systems began in the early 1900s when silica and mineral systems containing silica were focussed upon. Since then technical ceramics emerged and more emphasis has been placed on high temperature

  10. Simplified phase detector

    Science.gov (United States)

    Hershey, L. M.

    1979-01-01

    Tanlick sine-wave phase detector gives dc output voltage nearly proportional to phase difference between oscillator signal and reference signal. Device may be used for systems in which signal-to-noise ratio is high.

  11. Engineering holographic phase diagrams

    Science.gov (United States)

    Chen, Jiunn-Wei; Dai, Shou-Huang; Maity, Debaprasad; Zhang, Yun-Long

    2016-10-01

    By introducing interacting scalar fields, we tried to engineer physically motivated holographic phase diagrams which may be interesting in the context of various known condensed matter systems. We introduce an additional scalar field in the bulk which provides a tunable parameter in the boundary theory. By exploiting the way the tuning parameter changes the effective masses of the bulk interacting scalar fields, desired phase diagrams can be engineered for the boundary order parameters dual to those scalar fields. We give a few examples of generating phase diagrams with phase boundaries which are strikingly similar to the known quantum phases at low temperature such as the superconducting phases. However, the important difference is that all the phases we have discussed are characterized by neutral order parameters. At the end, we discuss if there exists any emerging scaling symmetry associated with a quantum critical point hidden under the dome in this phase diagram.

  12. Therapy Provider Phase Information

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Therapy Provider Phase Information dataset is a tool for providers to search by their National Provider Identifier (NPI) number to determine their phase for...

  13. Relationship of Acute Phase Reactants and Fat Accumulation during Treatment for Tuberculosis

    Directory of Open Access Journals (Sweden)

    Alejandro Sanchez

    2011-01-01

    Full Text Available Background. Tuberculosis causes inflammation and muscle wasting. We investigated how attenuation of inflammation relates to repletion of body composition during treatment in an underserved population. Design. Twenty-four patients (23 to 79 years old with pulmonary tuberculosis and inflammation (pretreatment albumin =2.96±0.13 g/dL, C-reactive protein [CRP] =6.71±1.34 μg/dL, and beta-2-microglobulin =1.68±0.10 μg/L were evaluated and had BIA over 24 weeks. Results. Weight increased by 3.02±0.81 kg (5.5%; =0.007 at week 4 and by 8.59±0.97 kg (15.6%; <0.0001 at week 24. Repletion of body mass was primarily fat, which increased by 2.09±0.52 kg at week 4 and 5.05±0.56 kg at week 24 (=0.004 and <0.0001 versus baseline. Fat-free mass (FFM, body cell mass (BCM, and phase angle did not increase until study week 8. Albumin rose to 3.65±0.14 g/dL by week 4 (<0.001 and slowly increased thereafter. CRP levels declined by ~50% at each interval visit. Conclusions. During the initial treatment, acute phase reactants returned towards normal. The predominant accrual of fat mass probably reflects ongoing, low levels of inflammation.

  14. Gas phase ion chemistry

    CERN Document Server

    Bowers, Michael T

    1979-01-01

    Gas Phase Ion Chemistry, Volume 2 covers the advances in gas phase ion chemistry. The book discusses the stabilities of positive ions from equilibrium gas-phase basicity measurements; the experimental methods used to determine molecular electron affinities, specifically photoelectron spectroscopy, photodetachment spectroscopy, charge transfer, and collisional ionization; and the gas-phase acidity scale. The text also describes the basis of the technique of chemical ionization mass spectrometry; the energetics and mechanisms of unimolecular reactions of positive ions; and the photodissociation

  15. CrowdPhase: crowdsourcing the phase problem

    OpenAIRE

    Jorda, Julien; Sawaya, Michael R.; Yeates, Todd O

    2014-01-01

    The human mind innately excels at some complex tasks that are difficult to solve using computers alone. For complex problems amenable to parallelization, strategies can be developed to exploit human intelligence in a collective form: such approaches are sometimes referred to as ‘crowdsourcing’. Here, a first attempt at a crowdsourced approach for low-resolution ab initio phasing in macromolecular crystallography is proposed. A collaborative online game named CrowdPhase was designed, which rel...

  16. Spectral phase conjugation via extended phase matching

    OpenAIRE

    Tsang, Mankei

    2005-01-01

    It is shown that the copropagating three-wave-mixing parametric process, with appropriate type-II extended phase matching and pumped with a short second-harmonic pulse, can perform spectral phase conjugation and parametric amplification, which shows a threshold behavior analogous to backward wave oscillation. The process is also analyzed in the Heisenberg picture, which predicts a spontaneous parametric down conversion rate in agreement with the experimental result reported by Kuzucu et al. [...

  17. Safety and immunogenicity of the DTP/HB /Hib combination vaccine: phase I study

    Directory of Open Access Journals (Sweden)

    Kusnandi Rusmil

    2013-11-01

    Full Text Available Background The World Health Organization (WHO has recommended the introduction of hepatitis B (HB and Haemophilus influenza type b (Hib vaccines into routine childhood vaccination programs. A new diptheria/tetanus/pertussis (DTP/hepatitis B/Hib pentavalent combination vaccine has been developed. Objective To evaluate the safety and immunogenicity of a new combination DTP/HB/Hib liquid vaccine in infants. Methods An open-label, uncontrolled, prospective intervention phase I study was conducted on 30 healthy infants aged 6−11 weeks. Each subject received 3 doses of DTP/HB/Hib vaccine, formulated by Bio Farma, 0.5 mL intramuscularly at the left anterolateral thigh region using a 25-gauge needle of 25 mm length. Subjects were followed for 1 month after administration of each vaccine dose to evaluate its safety, while serum anti-diphteria, tetanus, HBb, Hib, and pertussis antibodies were measured prior to the 1st dose and 1 month after the 3rd dose. Results Among 30 vaccinated subjects, 18 infants had fever within 24 hours after the first vaccination. Most cases of fever were mild in intensity and resolved within 24 hours. No other systemic or local reactions, or serious adverse events were observed in our subjects during the study. The immunogenicity results after 3rd vaccine dose showed that the geometric mean titer of the anti-polyribosylribitol phosphate (PRP antibody levels increased significantly from 0.0041μg/mL to 4.37 μg/mL after vaccination, and most infants had a fourfold or greater rise in antibody levels over their pre-injection levels. All subjects who received DTP/HB/Hib liquid vaccine had seroprotective antibodies against tetanus, diphtheria,a and hepatitis B, while 29/30 infants had seroprotective antibodies against pertussis. Conclusion This new diphtheria/tetanus/pertusis/hepatitis B/Hib combination vaccine has excellent safety profile and antibody responses in infants. These results encourage further clinical evaluation in

  18. Efficacy and Safety of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate in Asian Subjects with Human Immunodeficiency Virus 1 Infection: A Sub-Analysis of Phase 3 Clinical Trials

    Science.gov (United States)

    Sungkanuparph, Somnuek; Anekthananon, Thanomsak; Sax, Paul; DeJesus, Edwin; Edelstein, Howard; Nelson, Mark; DeMorin, Jennifer; Liu, Hui C.; Swamy, Raji; Bahn, Joonwoo; Hwang, SunJin; Yang, SangYoun; Ng, Christopher; Piontkowsky, David

    2016-01-01

    The efficacy and safety of a single tablet regimen (STR) of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) were analyzed in Phase 3 clinical trials in antiretroviral therapy (ART)-naïve and ART-experienced Asian subjects infected with human immunodeficiency virus (HIV)-1. Studies GS-US-236-102 and GS-US-236-103 were randomized, double-blind, placebo-controlled, 144-week studies conducted in ART-naïve subjects, comparing E/C/F/TDF versus efavirenz (EFV)/F/TDF or ritonavir-boosted atazanavir (ATV+RTV) plus emtricitabine/tenofovir DF (F/TDF), respectively. Studies GS-US-236-115 and GS-US-236-121 were randomized, open-label, 96-week long conducted in ART-experienced subjects, who switched to E/C/F/TDF from ritonavir-boosted protease inhibitors (PI+RTV)+F/TDF, or non-nucleoside reverse transcriptase inhibitors (NNRTI)+F/TDF regimens. The E/C/F/TDF appeared to have sustained efficacy and safety and was well tolerated in the small number of ART-naïve and ART-experienced Asian subjects. PMID:27704731

  19. Phase II study of gemcitabine and bexarotene (GEMBEX) in the treatment of cutaneous T-cell lymphoma

    Science.gov (United States)

    Illidge, T; Chan, C; Counsell, N; Morris, S; Scarisbrick, J; Gilson, D; Popova, B; Patrick, P; Smith, P; Whittaker, S; Cowan, R

    2013-01-01

    Background: Both gemcitabine and bexarotene are established single agents for the treatment of cutaneous T-cell lymphoma (CTCL). We investigated the feasibility and efficacy of combining these drugs in a single-arm phase II study. Methods: Cutaneous T-cell lymphoma patients who had failed standard skin-directed therapy and at least one prior systemic therapy were given four cycles of gemcitabine and concurrent bexarotene for 12 weeks. Responders were continued on bexarotene maintenance until disease progression or unacceptable toxicity. Results: The median age was 65 years, stage IB (n=5), stage IIA (n=2), stage IIB (n=8), stage III (n=8) and stage IVA (n=12), 17 patients were erythrodermic, 17 patients were B1, and 10 patients were both erythrodermic and B1. Thirty (86%) patients completed four cycles of gemcitabine. In all, 80.0% of patients demonstrated a reduction in modified Severity-Weighted Assessment Tool (mSWAT) score although the objective disease response rate at 12 weeks was 31% (partial response (PR) 31%) and at 24 weeks 14% (PR 14%, stable disease (SD) 23%, progressive disease (PD) 54%, not evaluable 9%). Median progression-free survival was 5.3 months and median overall survival was 21.2 months. Conclusion: The overall response rate of the combination did not reach the specified target to proceed further and is lower than that previously reported for gemcitabine as a single agent. PMID:24136145

  20. A Phase I Study of the Combination of Sorafenib With Temozolomide and Radiation Therapy for the Treatment of Primary and Recurrent High-Grade Gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Den, Robert B., E-mail: robert.den@jeffersonhospital.org [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Kamrava, Mitchell [Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland (United States); Sheng, Zhi [Howard Hughes Medical Institute, Programs in Gene Function and Expression and Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts (United States); Werner-Wasik, Maria; Dougherty, Erin; Marinucchi, Michelle [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Lawrence, Yaacov R. [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Center for Translational Research in Radiation Oncology, Sheba Medical Center (Israel); Hegarty, Sarah; Hyslop, Terry [Department of Biostatistics, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Andrews, David W.; Glass, Jon [Department of Neurosurgery, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Friedman, David P. [Department of Radiology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Green, Michael R. [Howard Hughes Medical Institute, Programs in Gene Function and Expression and Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts (United States); Camphausen, Kevin [Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland (United States); Dicker, Adam P. [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States)

    2013-02-01

    Purpose: Despite recent advances in the management of high-grade and recurrent gliomas, survival remains poor. Antiangiogenic therapy has been shown to be efficacious in the treatment of high-grade gliomas both in preclinical models and in clinical trials. We sought to determine the safety and maximum tolerated dose of sorafenib when combined with both radiation and temozolomide in the primary setting or radiation alone in the recurrent setting. Methods and Materials: This was a preclinical study and an open-label phase I dose escalation trial. Multiple glioma cell lines were analyzed for viability after treatment with radiation, temozolomide, or sorafenib or combinations of them. For patients with primary disease, sorafenib was given concurrently with temozolomide (75 mg/m{sup 2}) and 60 Gy radiation, for 30 days after completion of radiation. For patients with recurrent disease, sorafenib was combined with a hypofractionated course of radiation (35 Gy in 10 fractions). Results: Cell viability was significantly reduced with the combination of radiation, temozolomide, and sorafenib or radiation and sorafenib. Eighteen patients (11 in the primary cohort, 7 in the recurrent cohort) were enrolled onto this trial approved by the institutional review board. All patients completed the planned course of radiation therapy. The most common toxicities were hematologic, fatigue, and rash. There were 18 grade 3 or higher toxicities. The median overall survival was 18 months for the entire population. Conclusions: Sorafenib can be safely combined with radiation and temozolomide in patients with high-grade glioma and with radiation alone in patients with recurrent glioma. The recommended phase II dose of sorafenib is 200 mg twice daily when combined with temozolomide and radiation and 400 mg with radiation alone. To our knowledge, this is the first publication of concurrent sorafenib with radiation monotherapy or combined with radiation and temozolomide.

  1. Phase II Study of Erlotinib Plus Temozolomide During and After Radiation Therapy in Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma

    Science.gov (United States)

    Prados, Michael D.; Chang, Susan M.; Butowski, Nicholas; DeBoer, Rebecca; Parvataneni, Rupa; Carliner, Hannah; Kabuubi, Paul; Ayers-Ringler, Jennifer; Rabbitt, Jane; Page, Margaretta; Fedoroff, Anne; Sneed, Penny K.; Berger, Mitchel S.; McDermott, Michael W.; Parsa, Andrew T.; Vandenberg, Scott; James, C. David; Lamborn, Kathleen R.; Stokoe, David; Haas-Kogan, Daphne A.

    2009-01-01

    Purpose This open-label, prospective, single-arm, phase II study combined erlotinib with radiation therapy (XRT) and temozolomide to treat glioblastoma multiforme (GBM) and gliosarcoma. The objectives were to determine efficacy of this treatment as measured by survival and to explore the relationship between molecular markers and treatment response. Patients and Methods Sixty-five eligible adults with newly diagnosed GBM or gliosarcoma were enrolled. We intended to treat patients not currently treated with enzyme-inducing antiepileptic drugs (EIAEDs) with 100 mg/d of erlotinib during XRT and 150 mg/d after XRT. Patients receiving EIAEDs were to receive 200 mg/d of erlotinib during XRT and 300 mg/d after XRT. After XRT, the erlotinib dose was escalated until patients developed tolerable grade 2 rash or until the maximum allowed dose was reached. All patients received temozolomide during and after XRT. Molecular markers of epidermal growth factor receptor (EGFR), EGFRvIII, phosphatase and tensin homolog (PTEN), and methylation status of the promotor region of the MGMT gene were analyzed from tumor tissue. Survival was compared with outcomes from two historical phase II trials. Results Median survival was 19.3 months in the current study and 14.1 months in the combined historical control studies, with a hazard ratio for survival (treated/control) of 0.64 (95% CI, 0.45 to 0.91). Treatment was well tolerated. There was a strong positive correlation between MGMT promotor methylation and survival, as well as an association between MGMT promotor-methylated tumors and PTEN positivity shown by immunohistochemistry with improved survival. Conclusion Patients treated with the combination of erlotinib and temozolomide during and following radiotherapy had better survival than historical controls. Additional studies are warranted. PMID:19075262

  2. Efficacy and Safety of AmBisome in Combination with Sodium Stibogluconate or Miltefosine and Miltefosine Monotherapy for African Visceral Leishmaniasis: Phase II Randomized Trial

    Science.gov (United States)

    Wasunna, Monique; Njenga, Simon; Balasegaram, Manica; Alexander, Neal; Omollo, Raymond; Edwards, Tansy; Dorlo, Thomas P. C.; Musa, Brima; Ali, Mohammed Hassan Sharaf; Elamin, Mohammed Yasein; Kirigi, George; Kip, Anke E.; Schoone, Gerard J.; Hailu, Asrat; Olobo, Joseph; Ellis, Sally; Kimutai, Robert; Wells, Susan; Khalil, Eltahir Awad Gasim; Strub Wourgaft, Nathalie; Alves, Fabiana; Musa, Ahmed

    2016-01-01

    Background SSG&PM over 17 days is recommended as first line treatment for visceral leishmaniasis in eastern Africa, but is painful and requires hospitalization. Combination regimens including AmBisome and miltefosine are safe and effective in India, but there are no published data from trials of combination therapies including these drugs from Africa. Methods A phase II open-label, non-comparative randomized trial was conducted in Sudan and Kenya to evaluate the efficacy and safety of three treatment regimens: 10 mg/kg single dose AmBisome plus 10 days of SSG (20 mg/kg/day), 10 mg/kg single dose AmBisome plus 10 days of miltefosine (2.5mg/kg/day) and miltefosine alone (2.5 mg/kg/day for 28 days). The primary endpoint was initial parasitological cure at Day 28, and secondary endpoints included definitive cure at Day 210, and pharmacokinetic (miltefosine) and pharmacodynamic assessments. Results In sequential analyses with 49–51 patients per arm, initial cure was 85% (95% CI: 73–92) in all arms. At D210, definitive cure was 87% (95% CI: 77–97) for AmBisome + SSG, 77% (95% CI 64–90) for AmBisome + miltefosine and 72% (95% CI 60–85) for miltefosine alone, with lower efficacy in younger patients, who weigh less. Miltefosine pharmacokinetic data indicated under-exposure in children compared to adults. Conclusion No major safety concerns were identified, but point estimates of definitive cure were less than 90% for each regimen so none will be evaluated in Phase III trials in their current form. Allometric dosing of miltefosine in children needs to be evaluated. Trial Registration The study was registered with ClinicalTrials.gov, number NCT01067443 PMID:27627654

  3. Phase I Study of Oral Vinorelbine in Combination with Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC Using Two Different Schedules.

    Directory of Open Access Journals (Sweden)

    Natalia Sutiman

    Full Text Available This study aimed to evaluate the safety, tolerability and pharmacokinetics of the combination of oral vinorelbine with erlotinib using the conventional (CSV and metronomic (MSV dosing schedules in patients with advanced non-small cell lung cancer (NSCLC.This was an open-label, multiple dose-escalation phase I study. An alternating 3+3 phase I design was employed to allow each schedule to enroll three patients sequentially at each dose level. Thirty patients with Stage IIIB/IV NSCLC were treated with escalating doses of oral vinorelbine starting at 40 mg/m2 on day 1 and 8 in the CSV group (N = 16 and at 100 mg/week in the MSV group (N = 14. Erlotinib was administered orally daily.The maximum tolerated dose was vinorelbine 80 mg/m2 with erlotinib 100 mg in the CSV group and vinorelbine 120 mg/week with erlotinib 100 mg in the MSV group. Grade 3/4 toxicities included neutropenia (N = 2; 13% and hyponatremia (N = 1; 6% in the CSV group, and neutropenia (N = 5; 36% in the MSV group. Objective response was achieved in 38% and 29% in the CSV and MSV groups respectively. Vinorelbine co-administration did not significantly affect the pharmacokinetics of erlotinib and OSI-420 after initial dose. However, at steady-state, significantly higher Cmax, higher Cmin and lower CL/F of erlotinib were observed with increasing dose levels of vinorelbine in the CSV group. Significantly higher steady-state Cmin, Cavg and AUCss of erlotinib were observed with increasing dose levels of vinorelbine in the MSV group.Combination of oral vinorelbine with erlotinib is feasible and tolerable in both the CSV and MSV groups.ClinicalTrials.gov NCT00702182.

  4. A phase I study of the human anti-activin receptor-like kinase 1 antibody PF-03446962 in Asian patients with advanced solid tumors.

    Science.gov (United States)

    Doi, Toshihiko; Lee, Kyung-Hun; Kim, Tae-Min; Ohtsu, Atsushi; Kim, Tae Yong; Ikeda, Masafumi; Yoh, Kiyotaka; Gallo Stampino, Corrado; Hirohashi, Tomoko; Suzuki, Akiyuki; Fujii, Yosuke; Andrew Williams, James; Bang, Yung-Jue

    2016-07-01

    Preclinical studies suggest that ALK-1 signaling mediates a complementary angiogenesis pathway activated upon development of resistance to vascular endothelial growth factor (VEGF)-targeted therapies. Inhibition of ALK-1 signaling may lead to disruption of tumor angiogenesis and growth. We report findings from a multicenter, open-label, phase I study of the fully human anti-ALK-1 mAb PF-03446962 conducted in Japan and South Korea, in Asian patients with advanced solid tumors. The dose escalation Part 1 of the study was based on a standard 3 + 3 design (n = 16). In Part 2, patients were treated with PF-03446962 at 7 and 10 mg/kg (10/cohort), including patients with disease progression following prior VEGF receptor (R)-targeted therapy. Primary objectives were determination of the maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Secondary objectives included safety, pharmacokinetics, pharmacodynamics, and antitumor activity of PF-03446962. No dose-limiting toxicity (DLT) was noted in the 12 DLT-evaluable patients. Treatment was well tolerated. The MTD for biweekly intravenous administration was estimated to be 10 mg/kg and the RP2D 7 mg/kg. Treatment-related grades 1-3 thrombocytopenia was experienced by 27.8% patients. The most frequent nonhematologic treatment-related AEs were grades 1-2 pyrexia and epistaxis. Four patients (3/4 with hepatocellular carcinoma) developed telangiectasia suggesting vascular targeting and in vivo ALK-1 inhibition by PF-03446962. Stable disease for 12 weeks or more was observed in 25.7% of patients and in 44.4% of those with hepatocellular carcinoma. ALK-1 inhibition by PF-03446962 may represent a novel antiangiogenic strategy for patients with advanced solid malignancies complementary to current treatment with VEGF(R)-targeted inhibitors or chemotherapy. PMID:27075560

  5. Topological phase effects

    CERN Document Server

    Robbins, J M

    2010-01-01

    Quantum eigenstates undergoing cyclic changes acquire a phase factor of geometric origin. This phase, known as the Berry phase, or the geometric phase, has found applications in a wide range of disciplines throughout physics, including atomic and molecular physics, condensed matter physics, optics, and classical dynamics. In this article, the basic theory of the geometric phase is presented along with a number of representative applications. The article begins with an account of the geometric phase for cyclic adiabatic evolutions. An elementary derivation is given along with a worked example for two-state systems. The implications of time-reversal are explained, as is the fundamental connection between the geometric phase and energy level degeneracies. We also discuss methods of experimental observation. A brief account is given of geometric magnetism; this is a Lorenz-like force of geometric origin which appears in the dynamics of slow systems coupled to fast ones. A number of theoretical developments of the...

  6. Generalized Phase Contrast

    CERN Document Server

    Glückstad, Jesper

    2009-01-01

    Generalized Phase Contrast elevates the phase contrast technique not only to improve phase imaging but also to cross over and interface with diverse and seemingly disparate fields of contemporary optics and photonics. This book presents a comprehensive introduction to the Generalized Phase Contrast (GPC) method including an overview of the range of current and potential applications of GPC in wavefront sensing and phase imaging, structured laser illumination and image projection, optical trapping and manipulation, and optical encryption and decryption. The GPC method goes further than the restrictive assumptions of conventional Zernike phase contrast analysis and achieves an expanded range of validity beyond weak phase perturbations. The generalized analysis yields design criteria for tuning experimental parameters to achieve optimal performance in terms of accuracy, fidelity and light efficiency. Optimization can address practical issues, such as finding an optimal spatial filter for the chosen application, ...

  7. Interacting Weyl fermions: Phases, phase transitions and global phase diagram

    CERN Document Server

    Roy, Bitan; Juricic, Vladimir

    2016-01-01

    We study the effects of short-range interactions on a generalized three-dimensional Weyl semimetal, where the band touching points act as the (anti)monopoles of Abelian Berry curvature of strength $n$. We show that any local interaction has a \\emph{negative} scaling dimension $-2/n$. Consequently all Weyl semimetals are stable against weak short-range interactions. For sufficiently strong interactions, we demonstrate that the Weyl semimetal either undergoes a first order transition into a band insulator or a continuous transition into a symmetry breaking phase. A translational symmetry breaking axion insulator and a rotational symmetry breaking semimetal are two prominent candidates for the broken symmetry phase. At one loop level, the correlation length exponent for continuous transitions is $\

  8. Gymnastics in Phase Space

    Energy Technology Data Exchange (ETDEWEB)

    Chao, Alexander Wu; /SLAC

    2012-03-01

    As accelerator technology advances, the requirements on accelerator beam quality become increasingly demanding. Facing these new demands, the topic of phase space gymnastics is becoming a new focus of accelerator physics R&D. In a phase space gymnastics, the beam's phase space distribution is manipulated and precision tailored to meet the required beam qualities. On the other hand, all realization of such gymnastics will have to obey accelerator physics principles as well as technological limitations. Recent examples of phase space gymnastics include Emittance exchanges, Phase space exchanges, Emittance partitioning, Seeded FELs and Microbunched beams. The emittance related topics of this list are reviewed in this report. The accelerator physics basis, the optics design principles that provide these phase space manipulations, and the possible applications of these gymnastics, are discussed. This fascinating new field promises to be a powerful tool of the future.

  9. Phasing Into Retirement

    OpenAIRE

    Steven G. Allen; Clark, Robert L.; Linda S. Ghent

    2003-01-01

    To help workers navigate the transition from work to retirement more effectively, employers have been launching phased retirement programs, which allow older employees to work part-time and receive full retirement benefits. This paper examines the experience of the phased retirement system for tenured faculty in the University of North Carolina system over the years 1996-98. After phased retirement was introduced, there was a sizable increase in the overall separation rate in the system. The ...

  10. Cosmological phase transitions

    Energy Technology Data Exchange (ETDEWEB)

    Kolb, E.W. [Fermi National Accelerator Lab., Batavia, IL (United States)]|[Chicago Univ., IL (United States)

    1993-10-01

    If modern ideas about the role of spontaneous symmetry breaking in fundamental physics are correct, then the Universe should have undergone a series of phase transitions early in its history. The study of cosmological phase transitions has become an important aspect of early-Universe cosmology. In this lecture I review some very recent work on three aspects of phase transitions: the electroweak transition, texture, and axions.

  11. Dual phase evolution

    CERN Document Server

    Green, David G; Abbass, Hussein A

    2014-01-01

    This book explains how dual phase evolution operates in all these settings and provides a detailed treatment of the subject. The authors discuss the theoretical foundations for the theory, how it relates to other phase transition phenomena and its advantages in evolutionary computation and complex adaptive systems. The book provides methods and techniques to use this concept for problem solving. Dual phase evolution concerns systems that evolve via repeated phase shifts in the connectivity of their elements. It occurs in vast range of settings, including natural systems (species evolution, landscape ecology, geomorphology), socio-economic systems (social networks) and in artificial systems (annealing, evolutionary computing).

  12. Solid phase transformations II

    CERN Document Server

    Čermák, J

    2009-01-01

    This topical volume includes ten invited papers that cover selected areas of the field of solid phase transformations. The first two contributions represent a burgeoning branch; that of the computer simulation of physical phenomena. The following three articles deal with the thermodynamics of phase transformations as a basic theory for describing the phenomenology of phase changes in matter. The next paper describes the interconnections between structural stability and the electronic structure of phases. Two further articles are devoted to displacive transformations; a field where there are ma

  13. Dual Phase Cosmic Rays

    OpenAIRE

    Shurtleff, Richard

    2007-01-01

    A calculation based on flat spacetime symmetries shows how there can be two quantum phases. For one, extreme phase change determines a conventional classical trajectory and four-momentum, i.e. mass times four-velocity. The other phase occurs in an effective particle state, with the effective energy and momentum being the rate of change of the phase with respect to time and distance. A cosmic ray proton moves along a classical trajectory, but exists in an effective particle state with an effec...

  14. Sampling and analysis plan for phase II of the Bear Creek Valley treatability study Oak Ridge Y-12 Plant, Oak Ridge, Tennessee

    International Nuclear Information System (INIS)

    The Bear Creek Valley (BCV) Treatability Study is intended to provide site-specific data defining potential treatment technologies applicable to contaminated groundwater and surface water. This project directly supports Alternative 5 of the base action in the BCV Feasibility Study, and indirectly supports other alternatives through proof of concept. In that role, the ultimate goal is to install a treatment system that will remove uranium and nitrate from groundwater before it reaches Bear Creek. A secondary goal is the concurrent removal of technetium and several metals that impact ecological risk. This project is intended to produce hydraulic and treatment performance data required to design the treatment system to reach those goals. This project will also generate information that can be applied at other facilities within the Oak Ridge Reservation. This report is the sampling and analysis plan (SAP) for the field work component of Phase II of the BCV Treatability Study. Field work for this phase of the BCV Treatability Study consists of media testing. In-field continuous flow tests will be conducted over an extended time period (5 weeks) to generate data on long-term treatment effects on potential treatment media including sorbents and zero valent iron, over 28 weeks for constructed wetlands treatment, and over 24 weeks for algal mats treatment. The SAP addresses environmental sampling at the S-3 Site at the Oak Ridge Y-12 Plant. Samples will be taken from groundwater, effluent from test columns, effluent from an algal mat reactor, and effluent from a pilot-scale wetlands. This plan will be implemented as part of the BCV Phase II Treatability Study Best Management Practices Plan and in conjunction with the BCV Phase II Treatability Study Health and Safety Plan and the BCV Phase II Treatability Study Waste Management Plan

  15. UPVG phase 2 report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-08-01

    The Utility PhotoVoltaic Group (UPVG), supported by member dues and a grant from the US Department of Energy, has as its mission the acceleration of the use of cost-effective small-scale and emerging large-scale applications of photovoltaics for the benefit of electric utilities and their customers. Formed in October, 1992, with the support of the American Public Power Association, Edison Electric Institute, and the National Rural Electric Cooperative Association, the UPVG currently has 90 members from all sectors of the electric utility industry. The UPVG`s efforts as conceived were divided into four phases: Phase 0--program plan; Phase 1--organization and strategy development; Phase 2--creating market assurance; and Phase 3--higher volume purchases. The Phase 0 effort developed the program plan and was completed early in 1993. The Phase 1 goal was to develop the necessary background information and analysis to lead to a decision as to which strategies could be undertaken by utilities to promote greater understanding of PV markets and achieve increased volumes of PV purchases. This report provides the details of the UPVG`s Phase 2 efforts to initiate TEAM-UP, its multiyear, 50-MW hardware initiative.

  16. LIGHT NONAQUEOUS PHASE LIQUIDS

    Science.gov (United States)

    Nonaqueous phase liquids (NAPLS) are hydrocarbons that exist as a separate, immiscible phase when in contact with water and/or air. ifferences in the physical and chemical properties of water and NAPL result in the formation of a physical interface between the liquids which preve...

  17. UPVG phase 2 report

    International Nuclear Information System (INIS)

    The Utility PhotoVoltaic Group (UPVG), supported by member dues and a grant from the US Department of Energy, has as its mission the acceleration of the use of cost-effective small-scale and emerging large-scale applications of photovoltaics for the benefit of electric utilities and their customers. Formed in October, 1992, with the support of the American Public Power Association, Edison Electric Institute, and the National Rural Electric Cooperative Association, the UPVG currently has 90 members from all sectors of the electric utility industry. The UPVG's efforts as conceived were divided into four phases: Phase 0--program plan; Phase 1--organization and strategy development; Phase 2--creating market assurance; and Phase 3--higher volume purchases. The Phase 0 effort developed the program plan and was completed early in 1993. The Phase 1 goal was to develop the necessary background information and analysis to lead to a decision as to which strategies could be undertaken by utilities to promote greater understanding of PV markets and achieve increased volumes of PV purchases. This report provides the details of the UPVG's Phase 2 efforts to initiate TEAM-UP, its multiyear, 50-MW hardware initiative

  18. Pr