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Sample records for 24-week open-label phase

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

    Science.gov (United States)

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

    2009-01-01

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

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

    OpenAIRE

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

    2009-01-01

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

  3. Efficacy and tolerability of escitalopram in treatment of major depressive disorder with anxiety symptoms: a 24-week, open-label, prospective study in Chinese population

    Science.gov (United States)

    Jiang, Kaida; Li, Lingjiang; Wang, Xueyi; Fang, Maosheng; Shi, Jianfei; Cao, Qiuyun; He, Jincai; Wang, Jinan; Tan, Weihao; Hu, Cuili

    2017-01-01

    Background Significant anxiety symptoms are associated with poor clinical course and outcome in major depressive disorder (MDD). This single-arm, open-label study aimed to evaluate the efficacy and tolerability of escitalopram treatment in patients with MDD and anxiety symptoms. Methods Adult patients with MDD and anxiety symptoms (Montgomery–Asberg Depression Rating Scale [MADRS] ≥22 and Hamilton Anxiety Rating Scale [HAM-A] ≥14) were enrolled and received escitalopram (10–20 mg/day) treatment for 24 weeks. Symptom status was assessed by MADRS, 17-item-Hamilton Depression Rating Scale, HAM-A, and Clinical Global Impression Scale at baseline and the following visits. Quality of life was assessed by Short Form-12, and safety was evaluated by adverse events, laboratory investigations, vital signs, and physical findings. Results Overall, 200 of 318 (66.2%) enrolled patients completed the 24-week treatment. The remission (MADRS ≤10 and HAM-A ≤7) rate in the full analysis set (N=285) was 73.3% (95% confidence interval: 67.80, 78.38) at week 24. Mean (± standard deviation) MADRS total score was 33.4 (±7.13) and HAM-A score was 27.6 (±7.26) at baseline, which reduced to 6.6 (±10.18) and 6.0 (±8.39), respectively, at week 24. Patients with higher baseline depression and anxiety level took longer to achieve similar remission rates. Overall, 80 of the 302 (26.5%) patients included in the safety set reported at least 1 treatment-emergent adverse event (TEAE). Most frequently reported TEAEs (>2%) were headache (4.0%), nasopharyngitis (3.6%), nausea (3.0%), and dizziness (2.6%). Serious TEAEs were reported by 1.3% patients; no deaths were reported. Conclusion Escitalopram 10–20 mg/day was effective and well-tolerated in the long-term treatment of MDD with anxiety symptoms in adult Chinese population. PMID:28255239

  4. 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

  5. Efficacy and tolerability of escitalopram in treatment of major depressive disorder with anxiety symptoms: a 24-week, open-label, prospective study in Chinese population

    Directory of Open Access Journals (Sweden)

    Jiang KD

    2017-02-01

    Full Text Available Kaida Jiang,1 Lingjiang Li,2 Xueyi Wang,3 Maosheng Fang,4 Jianfei Shi,5 Qiuyun Cao,6 Jincai He,7 Jinan Wang,8 Weihao Tan,8 Cuili Hu8 1Psychiatry Department, Shanghai Mental Health Center, Shanghai, 2Psychiatry Department,The Second Xiangya Hospital, Central South University, Changsha, 3Psychiatry Department, First affiliated Hospital of Hebei Medical University, Shijiazhuang, 4Psychiatry Department, Wuhan Mental Health Center, Wuhan, 5Psychiatry Department, Hangzhou the 7th Hospital, Hangzhou, 6Psychology Department, Nanjing Drum Tower Hospital, Nanjing, 7Neurology Department, First affiliated Hospital of Wenzhou Medical University, Wenzhou, 8Medical Affairs Department, Xi’an Janssen Pharmaceutical Ltd., Beijing, People’s Republic of China Background: Significant anxiety symptoms are associated with poor clinical course and outcome in major depressive disorder (MDD. This single-arm, open-label study aimed to evaluate the efficacy and tolerability of escitalopram treatment in patients with MDD and anxiety symptoms. Methods: Adult patients with MDD and anxiety symptoms (Montgomery–Asberg Depression Rating Scale [MADRS] ≥22 and Hamilton Anxiety Rating Scale [HAM-A] ≥14 were enrolled and received escitalopram (10–20 mg/day treatment for 24 weeks. Symptom status was assessed by MADRS, 17-item-Hamilton Depression Rating Scale, HAM-A, and Clinical Global Impression Scale at baseline and the following visits. Quality of life was assessed by Short Form-12, and safety was evaluated by adverse events, laboratory investigations, vital signs, and physical findings. Results: Overall, 200 of 318 (66.2% enrolled patients completed the 24-week treatment. The remission (MADRS ≤10 and HAM-A ≤7 rate in the full analysis set (N=285 was 73.3% (95% confidence interval: 67.80, 78.38 at week 24. Mean (± standard deviation MADRS total score was 33.4 (±7.13 and HAM-A score was 27.6 (±7.26 at baseline, which reduced to 6.6 (±10.18 and 6.0 (±8

  6. 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

  7. 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.

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

    Science.gov (United States)

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

    2017-01-01

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

  9. 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.

  10. 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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    BACKGROUND: Cabozantinib is an oral inhibitor of tyrosine kinases including MET, VEGFR, and AXL. The randomised phase 3 METEOR trial compared the efficacy and safety of cabozantinib versus the mTOR inhibitor everolimus in patients with advanced renal cell carcinoma who progressed after previous...... VEGFR tyrosine-kinase inhibitor treatment. Here, we report the final overall survival results from this study based on an unplanned second interim analysis. METHODS: In this open-label, randomised phase 3 trial, we randomly assigned (1:1) patients aged 18 years and older with advanced or metastatic...

  12. 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).

  13. 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.

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

    Science.gov (United States)

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

    2014-07-03

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

  15. 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 <50 c/mL at week 24. Results. Mean change in HIV-1 RNA at day 8 was −1.43 log10 c/mL, and 69% of subjects achieved <50 c/mL at week 24. Multivariate analyses demonstrated a strong association between baseline DTG susceptibility and response. Response was most reduced in subjects with Q148 + ≥2 resistance-associated mutations. DTG 50 mg BID had a low (3%) discontinuation rate due to adverse events, similar to 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

  16. 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.

  17. 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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  19. Treatment with pentosan polysulphate in patients with MPS I: results from an open label, randomized, monocentric phase II study.

    Science.gov (United States)

    Hennermann, Julia B; Gökce, Seyfullah; Solyom, Alexander; Mengel, Eugen; Schuchman, Edward H; Simonaro, Calogera M

    2016-11-01

    Current treatment options for MPS I have limited effects on some organs, including the skeletal system. In MPS animal models pentosan polysulphate (PPS) reduces the concentrations of glycosaminoglycans (GAGs) in tissues and body fluids and improves cartilaginous and osseous pathologies. The goals of this study were to investigate primarily the safety and secondary the clinical effects, concerning mobility and pain, of PPS treatment in MPS I patients. Four MPS I-Hurler-Scheie/-Scheie patients aged 35.6 ± 6.4 years with one male were included in the study. All patients were on enzyme replacement therapy since 9.45 ± 3.75 years. PPS was applied subcutaneously in two patients with 1 mg/kg and in two patients with 2 mg/kg, weekly for 12 weeks and then biweekly for 12 weeks. The 24-week treatment with PPS was well tolerated by all patients. Urinary GAG concentrations were reduced from 4.13 ± 1.17 at baseline to 2.69 ± 0.36 mg/mmol creatinine after 24-week treatment with 1 mg/kg PPS, and from 6.71 ± 0.62 to 2.65 ± 0.09 mg/mmol creatinine with 2 mg/kg PPS. An improvement in range of motion was noted in three out of four patients. The pain intensity score was reduced from 4.5 ± 1.77 at baseline to 1.8 ± 0.47 after 24-week treatment with 1 mg/kg PPS; patients with 2 mg/kg PPS already had minimal pain at the start of the study. In conclusion, PPS treatment in a small number of adult MPS I patients was well tolerated and resulted in a significant reduction of urinary GAG excretion and in an improvement of joint mobility and pain.

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Salvatore Siena

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

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

    OpenAIRE

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2015-03-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  6. 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.

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

    Science.gov (United States)

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

    2017-02-01

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

  8. 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.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  11. 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...

  12. 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...

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

    Directory of Open Access Journals (Sweden)

    Gloria Solano-Aguilar

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

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

    Science.gov (United States)

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

    2014-01-01

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

  15. 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

  16. 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

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

    Science.gov (United States)

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

    2016-01-01

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

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

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    P Patterson

    2012-11-01

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

  19. 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.

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    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.

  20. 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.

  1. Efalizumab in the Treatment of Scalp, Palmoplantar and Nail Psoriasis: Results of a 24-Week Latin American Study

    Science.gov (United States)

    Takahashi, María Denise; Chouela, Edgardo Néstor; Dorantes, Gladys Leon; Roselino, Ana Maria; Santamaria, Jesùs; Allevato, Miguel Angel; Cestari, Tania; de Aillaud, Maria Eugenia Manzanera; Stengel, Fernando Miguel; Licu, Daiana

    2010-01-01

    Introduction Plaque-type psoriasis affecting the nails, scalp, hands or feet can often be difficult to treat; for example, topical treatments and phototherapy may not penetrate the nail plate or scalp. The objective of this large, international, multicentre study was to investigate the efficacy of efalizumab in a Latin American population of adult patients with moderate-to-severe chronic plaque psoriasis who were candidates for systemic therapy or phototherapy. Methods Eligible patients were enrolled in a 24-week, open-label, single-arm, Phase IIIb/IV study of continuous treatment with subcutaneous efalizumab, 1.0 mg/kg/wk. Involvement of the nails, scalp, or hands or feet was assessed using the Nail Psoriasis Severity Index (NAPSI), the Psoriasis Scalp Severity Index (PSSI), or the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI), respectively. Missing data were handled using a last observation carried forward or nonresponder imputation approach. Results Of the 189 patients who received treatment, 112 patients had nail involvement, 172 had scalp involvement, and 19 had palmoplantar disease at baseline. At Week 24, ≥50% improvement on the NAPSI, PSSI and PPPASI was observed in 31%, 71% and 68% of patients, respectively, whereas ≥75% improvement on these scores was observed in 17%, 52% and 63%, respectively. Descriptive statistics showed lower NAPSI-75 and higher PSSI-75 and -50 response rates among patients with higher baseline scores. Conclusions This open-label, uncontrolled study provides supportive evidence of the potential of efalizumab as a treatment for nail, scalp and palmoplantar psoriasis. PMID:20428227

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

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    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.

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

    Science.gov (United States)

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

    2006-01-01

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

  4. Atomoxetine Open-Label Trial in ADHD

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    J Gordon Millichap

    2002-07-01

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

  5. 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.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  7. 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

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    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

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

    Science.gov (United States)

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

    2014-06-01

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

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

    Science.gov (United States)

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

    2014-06-01

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

  10. 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

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

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    Yildiz P

    2016-11-01

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

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

    Science.gov (United States)

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

    2015-12-01

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

  13. Virological efficacy of 24-week fozivudine-based regimen in ART-naive patients from Tanzania and Côte d’Ivoire

    Science.gov (United States)

    Kroidl, Arne; Ello, Frederic; Mgaya, Jimson; Lennemann, Tessa; Moh, Raoul; Maganga, Lucas; Eholie, Serge; Pruvost, Alain; Saathoff, Elmar; Girard, Pierre-Marie; Zuhse, Ralph; von Massow, Friedrich; Anglaret, Xavier; Hoelscher, Michael; Danel, Christine

    2017-01-01

    Objective: Use of zidovudine (ZDV) in antiretroviral therapy is limited by toxicity and twice daily (b.i.d.) dosing. Fozivudine (FZD) is a ZDV prodrug, which is activated intracellularly to ZDV-monophosphate especially in mononuclear cells but not in bone marrow cells. FZD promises improved myelotoxicity and once daily (o.d.) dosing. Design: Randomized clinical trial. Methods: We conducted an open-label, phase II, proof-of-concept trial investigating three different FZD doses (800 mg o.d., 600 mg b.i.d., 1200 mg o.d.) versus ZDV (300 mg b.i.d.) in combination with lamivudine and efavirenz in HIV-infected, ART-naive patients from Tanzania and Côte d’Ivoire. The primary objective was to demonstrate virological efficacy after 24 weeks in intent-to treat and per-protocol analysis. Secondary endpoints included safety and pharmacokinetic outcomes. Results: Of 119 participants included in the intent-to treat analysis, HIV RNA less than 50 copies/ml at 24 weeks was observed in 64 of 88 (73%) patients in the combined FZD arms versus 24 of 31 (77%) in the ZDV arm (RR 0.94, 95% confidence interval 0.75–1.18). In the per-protocol analysis, responses were 64 of 77 (87%) versus 23 of 29 (79%), respectively (RR 1.09, 95% confidence interval 0.89–1.34). Outcomes were similar between FZD arms. Overall, treatments were well tolerated. Severe or worse anaemia occurred in two cases (one related to FZD, one to ZDV), grade III/IV neutropenia was less frequent in FZD compared with ZDV arms (22 versus 42%, P = 0.035). Pharmacokinetic analysis supported o.d. administration of FZD. Conclusion: Virological 24-week efficacy was demonstrated in b.i.d. and o.d. administered FZD-based regimens. Reduced myelotoxicity of FZD needs to be confirmed in a larger trial. PMID:27941394

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

    Science.gov (United States)

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

    2012-07-01

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

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

    Science.gov (United States)

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

    2017-02-01

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

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

    Science.gov (United States)

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

    2015-04-01

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

  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.

  18. HCVerso3: An Open-Label, Phase IIb Study of Faldaprevir and Deleobuvir with Ribavirin in Hepatitis C Virus Genotype-1b-Infected Patients with Cirrhosis and Moderate Hepatic Impairment

    Science.gov (United States)

    Sarrazin, Christoph; Manns, Michael; Calleja, Jose Luis; Garcia-Samaniego, Javier; Forns, Xavier; Kaste, Renee; Bai, Xiaofei; Wu, Jing; Stern, Jerry O.

    2016-01-01

    This study evaluated the interferon-free, oral combination of deleobuvir (non-nucleoside HCV NS5-RNA-polymerase inhibitor) and faldaprevir (HCV NS3/4A-protease inhibitor) with ribavirin in patients with HCV genotype-1b and moderate (Child-Pugh B [CPB], n = 17) or mild hepatic impairment (Child-Pugh A [CPA], n = 18). Patients received faldaprevir 120 mg and deleobuvir (600 mg [CPA], 400 mg [CPB]) twice-daily with weight-based ribavirin for 24 weeks. Baseline characteristics were similar between groups. Among CPA patients, 13/18 completed treatment; discontinuations were for adverse events (AEs, n = 1), lack of efficacy (n = 3) and withdrawal (n = 1). Among CPB patients, 8/17 completed treatment; discontinuations were for AEs (n = 6), withdrawal (n = 1) and ‘other’ (n = 2). Sustained virologic response at post-treatment Week 12 (SVR12) was achieved by 11 (61%) CPA patients (95% confidence interval: 38.6%–83.6%) and 9 (53%) CPB patients (95% confidence interval: 29.2%–76.7%), including most CPA (11/16) patients with Week 4 HCV RNA CPB (8/9) patients with Week 4 HCV RNA CPB patients with Week 4 HCV RNA CPB patients and 1 (6%) CPA patient. Plasma trough concentrations of deleobuvir and faldaprevir were not substantially different between the CPA and CPB groups. In conclusion, in this small study the safety and efficacy profiles for 24 weeks of treatment with faldaprevir+deleobuvir+ribavirin in patients with mild or moderate hepatic impairment were consistent with the safety and efficacy profile of this regimen in non-cirrhotic patients. Faldaprevir+deleobuvir+ribavirin resulted in SVR12 in 53–61% of patients: proportions achieving SVR4 but not SVR12 were higher than in non-cirrhotic patients and overall response rates were lower than rates reported with other all-oral regimens in patients with cirrhosis. Trial Registration: ClinicalTrials.gov NCT01830127. PMID:28030579

  19. 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

  20. 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

  1. 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

  2. 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

  3. Open-Label Memantine in Fragile X Syndrome

    Science.gov (United States)

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  6. 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

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

    Science.gov (United States)

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

    2016-03-01

    Renal impairment is associated with poor prognosis in myeloma. This analysis of the pivotal phase 3 FIRST trial examined the impact of renally adapted dosing of lenalidomide and dexamethasone on outcomes of patients with different degrees of renal impairment. Transplant-ineligible patients not requiring dialysis were randomized 1:1:1 to receive continuous lenalidomide and dexamethasone until disease progression (n=535) or for 18 cycles (72 weeks; n=541), or melphalan, prednisone, and thalidomide for 12 cycles (72 weeks; n=547). Follow-up is ongoing. Patients were grouped by baseline creatinine clearance into no (≥ 80 mL/min [n=389]), mild (≥ 50 to Celgene Corporation.

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

    Science.gov (United States)

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

    2017-02-01

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

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

    Science.gov (United States)

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

    2011-02-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  12. 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.

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

    Science.gov (United States)

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

    2016-01-01

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

  14. Effects of 24-week Tai Chi exercise on the knee and ankle proprioception of older women.

    Science.gov (United States)

    Chang, Shuwan; Zhou, Jihe; Hong, Youlian; Sun, Wei; Cong, Yan; Qin, Meiqin; Lian, Jianhua; Yao, Jian; Li, Weiping

    2016-01-01

    This study examined the effects of regular Tai Chi (TC) exercise on the kinaesthesia of the knee and ankle joints of older women. A total of 43 women aged 55-68 years participated in this study. In a 24-week study period, the TC group (n = 22) underwent an organized TC exercise, whereas the control group (n = 21) maintained a sedentary lifestyle. Customized instruments were used to measure the threshold for the detection of the passive motion of the knee and ankle joints. After 24 weeks, the TC group showed a significantly smaller threshold for the detection of passive motion of knee extension (31.4%, p = 0.009), knee flexion (27.0%, p = 0.044), and ankle dorsal flexion (28.9%, p = 0.014) than the control group. Other comparisons showed no significant differences. The 24-week TC exercise benefited the lower-limb kinaesthesia of the knee joint flexion and extension and ankle dorsal flexion.

  15. Effects of 24 weeks of Tai Chi Exercise on Postural Control among Elderly Women.

    Science.gov (United States)

    Zhou, Jihe; Chang, Shuwan; Cong, Yan; Qin, Meiqin; Sun, Wei; Lian, Jianhua; Yao, Jian; Li, Weiping; Hong, Youlian

    2015-01-01

    This study examined the effects of 24 weeks of Tai Chi Quan on the postural control of elderly women. A total of 43 women aged 55-68 years participated in the study. A Tai Chi group (n = 22) underwent an organized Tai Chi exercise, whereas the control group (n = 21) maintained a habitual, no-regular-exercise lifestyle. A Good Balance tester (Metitur, Finland) was used to measure the time, paths and velocity of the center of pressure (COP) of subjects during stance while shifting COP to targeted positions shown on a monitor. After 24 weeks, the Tai Chi group showed significantly shorter total (18.6%, p = 0.005), mediolateral (21.9%, p = 0.002) and anteroposterior (18.3%, p = 0.002) COP sway paths than the control group. The results indicate that 24 weeks of the Tai Chi exercise improved the efficiency of postural control for elderly women.

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

    Science.gov (United States)

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

    2007-09-01

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

  17. 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.

  18. Orlistat 60 mg reduces visceral adipose tissue: a 24-week randomized, placebo-controlled, multicenter trial.

    Science.gov (United States)

    Smith, Steven R; Stenlof, Kaj S; Greenway, Frank L; McHutchison, John; Schwartz, Susan M; Dev, Vidhu B; Berk, Evan S; Kapikian, Roxanne

    2011-09-01

    It is well established that abdominal obesity or upper body fat distribution is associated with increased risk of metabolic and cardiovascular disease. The purpose of the present study was to determine if a 24 week weight loss program with orlistat 60 mg in overweight subjects would produce a greater change in visceral adipose tissue (VAT) as measured by computed tomography (CT) scan, compared to placebo. The effects of orlistat 60 mg on changes in total fat mass (EchoMRI-AH and BIA), ectopic fat (CT) and glycemic variables were assessed. One-hundred thirty-one subjects were randomized into a multicenter, double-blind placebo controlled study in which 123 subjects received at least one post baseline efficacy measurement (intent-to-treat population). Both orlistat-and placebo-treated subjects significantly decreased their VAT at 24 weeks with a significantly greater loss of VAT by orlistat treated subjects (-15.7% vs. -9.4%, P orlistat-treated subjects had significantly greater weight loss (-5.93 kg vs. -3.94 kg, P orlistat 60 mg significantly reduces VAT in addition to total body fat compared to placebo treated subjects after a 24 week weight loss program. These results suggest that orlistat 60 mg may be an effective weight loss tool to reduce metabolic risk factors associated with abdominal obesity.

  19. 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

  20. Successful caspofungin treatment of persistent candidemia in extreme prematurity at 23 and 24 weeks' gestation.

    Science.gov (United States)

    Jeon, Ga Won; Sin, Jong Beom

    2014-03-01

    Systemic fungal infection continues to be a major cause of mortality in extremely low-birth-weight premature infants. Amphotericin B has been recommended as the primary treatment; however, its use is limited due to drug-induced nephrotoxicity and amphotericin B-resistant candidemia. Caspofungin therapy was initiated in seven extremely premature infants at 23 and 24 weeks' gestation with persistent systemic candidiasis despite liposomal amphotericin B treatment. The gestational age was 23(+1)-24(+6) weeks, and birth weight was 530-825 g. Of the seven patients, the peripheral blood cultures of six patients were positive for Candida parapsilosis and one had positive culture for Candida albicans. The dosage of caspofungin was 2 mg/kg/day, and the mean treatment duration was 14 days. All of the persistent candidemia resolved on caspofungin therapy. There was no recurrent candidemia after discontinuing caspofungin. There were no adverse effects, hepatotoxicity, nephrotoxicity, anemia, or thrombocytopenia. Caspofungin successfully treated persistent candidemia in extremely premature infants at 23 and 24 weeks' gestational age.

  1. A physical demands analysis of the 24-week British Army Parachute Regiment recruit training syllabus.

    Science.gov (United States)

    Wilkinson, David M; Rayson, Mark P; Bilzon, James L J

    2008-05-01

    This study assessed the physical demands of the 24-week Combined Infantryman's Course (CIC) for Parachute Regiment (Para) recruits and developed physical selection standards for applicants. Fifty recruits were monitored over five separate periods (35 d in total during weeks 1-2, 5, 9, 15 and 19-20). Energy expenditure (doubly labelled water), physical activity (accelerometry) and cardiovascular strain (% heart rate reserve) were measured. There was no overall progression in both the levels of physiological stress (physical activity counts and energy expenditure) and resultant cardiovascular strain during the first nine weeks of training. Applicants' 2.4 km run time and static lift strength measured at selection predicted 10 mile loaded march performance at the end of CIC Para. The introduction of job-related selection procedures and a more progressive approach to training has reduced the incidence of medical discharge from 14.4% to 5.1% and increased overall pass rates from 43% to 58%.

  2. First expirience of adalimumab administration in Russia: preliminary results of an open 24 week study

    Directory of Open Access Journals (Sweden)

    E L Luchichina

    2008-01-01

    Full Text Available Introduction. Adalimumab (Humira is a monoclonal anti-TNFa antibody fully identical to human antibodies, a member of group of TNFa blockers which are now the main biological drugs for the treatment of rheumatoid arthritis (RA. Till recently adalimumab was little known in Russia. Material and methods. 24 pts (2 male and 22 female were included in an open 24-week clinical study of adalimumab in active RA. Mean duration of the disease was 6,4 years. 5 pts had early RA. In all pts DAS28 was higher than 5,1. All pts earlier received main traditional DMARDs (methotrexate, leflunomide, sulfasalazine and steroids without significant improvement. All pts were treated on an outpatient basis. Adalimumab 40 mg was injected subcutaneously with 2 weeks intervals during 24 weeks. Results. 22 from 24 pts (91,7% completed full course of treatment with adalimumab. All outcome measures (pt self assessment on VAS, DAS28,HAQ, CRP showed fast and sustained improvement. Good effect according to EULAR criteria was achieved in 8 (33,4%, moderate — in 14 (58,3% pts and 2 pts (8,3% did not respond to the treatment. Effect did not depend on age, previous treatment, comorbid diseases and disease duration. During follow up period serious adverse events and tuberculosis did not appear in this group of pts. Conclusion. Adalimumab is a highly effective biological drug from the group of TNFa blockers which is particularly useful for the treatment of RA resistant to conventional therapy on an outpatient basis.

  3. Physical and psychological benefits of a 24-week traditional dance program in breast cancer survivors.

    Science.gov (United States)

    Kaltsatou, Antonia; Mameletzi, Dimitra; Douka, Stella

    2011-04-01

    The purpose of the present study was to evaluate the influence of a mixed exercise program, including Greek traditional dances and upper body training, in physical function, strength and psychological condition of breast cancer survivors. Twenty-seven women (N = 27), who had been diagnosed and surgically treated for breast cancer, volunteered to participate in this study. The experimental group consisted of 14 women with mean age 56.6 (4.2) years. They attended supervised Greek traditional dance courses and upper body training (1 h, 3 sessions/week) for 24 weeks. The control group consisted of 13 sedentary women with mean age 57.1 (4.1) years. Blood pressure, heart rate, physical function (6-min walking test), handgrip strength, arm volume and psychological condition (Life Satisfaction Inventory and Beck Depression Inventory) were evaluated before and after the exercise program. The results showed significant increases of 19.9% for physical function, 24.3% for right handgrip strength, 26.1% for left handgrip strength, 36.3% for life satisfaction and also a decrease of 35% for depressive symptoms in the experimental group after the training program. Significant reductions of 9% for left hand and 13.7% for right hand arm volume were also found in the experimental group. Consequently, aerobic exercise with Greek traditional dances and upper body training could be an alternative choice of physical activity for breast cancer survivors, thus promoting benefits in physical function, strength and psychological condition.

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

    Science.gov (United States)

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

    2010-01-01

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

  5. 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…

  6. 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

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

    NARCIS (Netherlands)

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

    2006-01-01

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

  8. 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

  9. 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…

  10. 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

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

    OpenAIRE

    2009-01-01

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

  12. 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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2009-01-01

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

  15. EE-drospirenone-levomefolate calcium versus EE-drospirenone + folic acid: folate status during 24 weeks of treatment and over 20 weeks following treatment cessation

    Directory of Open Access Journals (Sweden)

    Diefenbach K

    2013-04-01

    Full Text Available Konstanze Diefenbach,1 Dietmar Trummer,1 Frank Ebert,1 Michael Lissy,2 Manuela Koch,2 Beate Rohde,1 Hartmut Blode3 1Bayer HealthCare Pharmaceuticals, Berlin, Germany; 2Nuvisan GmbH, Neu-Ulm, Germany; 3Bayer HealthCare Pharmaceuticals Global R&D Center, Beijing, People's Republic of China Background: Adequate folate supplementation in the periconceptional phase is recommended to reduce the risk of neural tube defects. Oral contraceptives may provide a reasonable delivery vehicle for folate supplementation before conception in women of childbearing potential. This study aimed to demonstrate that a fixed-dose combination of an oral contraceptive and levomefolate calcium leads to sustainable improvements in folate status compared with an oral contraceptive + folic acid. Methods: This was a double-blind, randomized, parallel-group study in which 172 healthy women aged 18–40 years received ethinylestradiol (EE-drospirenone-levomefolate calcium or EE-drospirenone + folic acid for 24 weeks (invasion phase, and EE-drospirenone for an additional 20 weeks (folate elimination phase. The main objective of the invasion phase was to examine the area under the folate concentration time-curve for plasma and red blood cell (RBC folate, while the main objective of the elimination phase was to determine the duration of time for which RBC folate concentration remained ≥ 906 nmol/L after cessation of EE-drospirenone-levomefolate calcium. Results: Mean concentration-time curves for plasma folate, RBC folate, and homocysteine were comparable between treatment groups during both study phases. During the invasion phase, plasma and RBC folate concentrations increased and approached steady-state after about 8 weeks (plasma or 24 weeks (RBC. After cessation of treatment with levomefolate calcium, folate concentrations decreased slowly. The median time to RBC folate concentrations falling below 906 nmol/L was 10 weeks (95% confidence interval 8–12 weeks after cessation

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

    Science.gov (United States)

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

    2012-12-01

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

  17. 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.

  18. 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

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

    Science.gov (United States)

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

    2013-01-01

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

  20. 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

  1. 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...

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2005-10-01

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

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

    Science.gov (United States)

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

    2016-07-01

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

  5. 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...

  6. 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.

  7. 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

  8. 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

  9. 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...

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    I. V. Shirinsky

    2008-01-01

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

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

    Science.gov (United States)

    Lyons, Kelly E; Pahwa, Rajesh

    2009-10-30

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

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

    Science.gov (United States)

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

    2016-06-01

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

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

    Science.gov (United States)

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

    2001-10-01

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

  15. 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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Praveen Oberai

    2016-01-01

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

  18. 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.

  19. 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

  20. 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.

  1. 24-weeks Pilates-aerobic and educative training to improve body fat mass in elderly Serbian women

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    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.

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

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    Priyanka Sethi

    2015-01-01

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

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

    Science.gov (United States)

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

    2007-01-30

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

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

    Science.gov (United States)

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

    2013-12-01

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

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

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    Vazquez JA

    2016-09-01

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

  7. 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.

  8. 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

  9. A randomized, open-label, controlled trial of gabapentin and phenobarbital in the treatment of alcohol withdrawal.

    Science.gov (United States)

    Mariani, John J; Rosenthal, Richard N; Tross, Susan; Singh, Prameet; Anand, Om P

    2006-01-01

    Gabapentin was compared with phenobarbital for the treatment of alcohol withdrawal in a randomized, open-label, controlled trial in 27 inpatients. There were no significant differences in the proportion of treatment completers between treatment groups or the proportion of patients in each group requiring rescue medication for breakthrough signs and symptoms of alcohol withdrawal. There were no significant treatment differences in withdrawal symptoms or psychological distress, nor were there serious adverse events. These findings suggest that gabapentin may be as effective as phenobarbital in the treatment of alcohol withdrawal. Given gabapentin's favorable pharmacokinetic profile, further study of its effectiveness in treating alcohol withdrawal is warranted.

  10. Prospective open-label study of add-on and monotherapy topiramate in civilians with chronic nonhallucinatory posttraumatic stress disorder

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    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.

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

    Directory of Open Access Journals (Sweden)

    Tarik Asselah

    Full Text Available Shortening duration of peginterferon-based HCV treatment reduces associated burden for patients. Primary objectives of this study were to assess the efficacy against the minimally acceptable response rate 12 weeks post-treatment (SVR12 and safety of simeprevir plus PR in treatment-naïve HCV GT1 patients treated for 12 weeks. Additional objectives included the investigation of potential associations of rapid viral response and baseline factors with SVR12.In this Phase III, open-label study in treatment-naïve HCV GT1 patients with F0-F2 fibrosis, patients with HCV-RNA 12-week regimen.Overall SVR12 rate (66% was below the target of 80%, indicating that shortening of treatment with simeprevir plus PR to 12 weeks based on very early response is not effective. However, baseline factors associated with higher SVR12 rates were identified. Therefore, while Week 2 response alone is insufficient to predict efficacy, GT1 patients with favourable baseline factors may benefit from a shortened simeprevir plus PR regimen.ClinicalTrials.gov NCT01846832.

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

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    Pandina Gahan

    2012-06-01

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

  13. The effects of amisulpride on five dimensions of psychopathology in patients with schizophrenia: a prospective open- label study

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    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.

  14. Long-term safety and tolerability of open-label aripiprazole augmentation of antidepressant therapy in major depressive disorder

    Directory of Open Access Journals (Sweden)

    Berman R

    2011-05-01

    Full Text Available Robert M Berman1, Michael E Thase2, Madhukar H Trivedi3, James A Hazel4, Sabrina Vogel Marler5, Robert D McQuade6, William Carson7, Ross A Baker8, Ronald N Marcus91Neuroscience Global Clinical Research Bristol-Myers Squibb, Wallingford, CT, USA; 2Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; 3Division of Mood Disorders Research Program and Clinic, University of Texas Southwestern Medical School, Dallas, TX, USA; 4Neuroscience Global Clinical Research, Bristol-Myers Squibb, Wallingford, CT, USA; 5Global Biometric Sciences, Bristol-Myers Squibb, Wallingford, CT, USA; 6Global Medical Affairs at Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, NJ, USA; 7Global Clinical Development, Otsuka Pharmaceutical Development and Commercialization Inc, Princeton, NJ, USA; 8Neuroscience Medical Strategy, Bristol-Myers Squibb Company, Plainsboro, NJ, USA; 9Neuroscience Global Clinical Research, Bristol-Myers Squibb, Wallingford, CT, USABackground: Effective management of major depressive disorder often includes the long-term use of multiple medications, and the longer-term utility and safety of adjunctive aripiprazole has not been evaluated in a controlled setting.Patients and methods: Patients (n = 706 completing one of two 14-week double-blind studies of aripiprazole augmentation, as well as de novo patients (n = 296 nonresponsive to current antidepressant therapy, were enrolled in this open-label study. Patients received open-label aripiprazole for up to 52 weeks.Results: Open-label treatment was completed by 323 patients (32.2%. At endpoint (n = 987, the mean dose of aripiprazole was 10.1 mg/day. Common (>15% of patients spontaneously reported adverse events were akathisia (26.2%, fatigue (18.0%, and weight gain (17.1%. The incidence of serious adverse events was 4.0%. Four spontaneous reports of possible tardive dyskinesia were submitted (0.4%; all resolved within 45 days of drug

  15. Escitalopram in the treatment of patients with schizophrenia and obsessive-compulsive disorder: an open-label, prospective study.

    Science.gov (United States)

    Stryjer, Rafael; Dambinsky, Yael; Timinsky, Igor; Green, Tamar; Kotler, Moshe; Weizman, Abraham; Spivak, Baruch

    2013-03-01

    The current data suggest that up to 50% of patients with schizophrenia have obsessive-compulsive (OC) symptoms coexisting with psychosis and between 7.8 and 46% of schizophrenia patients also have full-blown obsessive-compulsive disorder (OCD). The aim of this study was to examine the efficacy of the most selective serotonin reuptake inhibitor escitalopram in the management of OCD in schizophrenia patients. The study was an open-label prospective trial of 12 weeks' duration in which escitalopram at a dose of up to 20 mg/day was added to the existing antipsychotic drug regimen in schizophrenia patients with OCD. Fifteen patients (10 men/five women) with the diagnosis of schizophrenia and OCD were recruited for the study (mean age: 39±14, range 21-61 years) and received escitalopram according to the study design. A significant improvement was observed in the total Yale Brown Obsessive-Compulsive Scale (Y-BOCS) scores and in the scores of both the Y-BOCS-Obsession and the Y-BOCS-Compulsion subscale at the end point. In addition, a significant improvement was observed in the total scores of the Positive and Negative Syndrome Scale and particularly in scores of anxiety, tension, depression, and preoccupation items. No adverse effects of escitalopram were reported by patients during the trial. In our prospective 12-week open-label study, escitalopram 20 mg/day was well tolerated and improved OC symptoms in schizophrenia patients. Our preliminary results are encouraging and a double-blind randomized study is required to confirm our results.

  16. 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

  17. Phase IV open-label study of the efficacy and safety of deferasirox after allogeneic stem cell transplantation.

    Science.gov (United States)

    Vallejo, Carlos; Batlle, Montserrat; Vázquez, Lourdes; Solano, Carlos; Sampol, Antonia; Duarte, Rafael; Hernández, Dolores; López, Javier; Rovira, Montserrat; Jiménez, Santiago; Valcárcel, David; Belloch, Vicente; Jiménez, Mónica; Jarque, Isidro

    2014-10-01

    This is the first prospective study of deferasirox in adult allogeneic hematopoietic stem cell transplant recipients with transfusional iron overload in hematologic malignancies. Patients at least six months post transplant were treated with deferasirox at a starting dose of 10 mg/kg/day for 52 weeks or until serum ferritin was less than 400 ng/mL on two consecutive occasions. Thirty patients were enrolled and 22 completed the study. A significant reduction from baseline in median serum ferritin and in liver iron concentration at 52 weeks was observed in the overall population: from 1440 to 755.5 ng/mL (P=0.002) and from 14.5 to 4.6 mg Fe/g dw (P=0.0007), respectively. Reduction in serum ferritin in patients who did not discontinue deferasirox therapy was significantly greater than that found in those who prematurely discontinued the treatment (from 1541 to 581 ng/mL vs. from 1416 to 1486 ng/mL; P=0.008). Drug-related adverse events, reported in 17 patients (56.7%), were mostly mild to moderate in severity. There were no drug-related serious adverse events. Twelve patients (40.0%) showed an increase of over 33% in serum creatinine compared to baseline and greater than the upper limit of normal on two consecutive visits. Two patients (6.7%) with active graft-versus-host disease showed an increase in alanine aminotransferase exceeding 10 times upper limit of normal; both resolved. In this prospective study, deferasirox provided a significant reduction in serum ferritin and liver iron concentration over one year of treatment in allogeneic hematopoietic stem cell transplant recipients with iron overload. In addition, the majority of adverse events related to deferasirox were mild or moderate in severity. (clinicaltrials.gov identifier:01335035).

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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

  3. Effects of Ipragliflozin on Diabetic Nephropathy and Blood Pressure in Patients With Type 2 Diabetes: An Open-Label Study

    Science.gov (United States)

    Ito, Daisuke; Ikuma-Suwa, Emi; Inoue, Kazuyuki; Kaneko, Kimie; Yanagisawa, Morifumi; Inukai, Kouichi; Noda, Mitsuhiko; Shimada, Akira

    2017-01-01

    Background Sodium-glucose cotransporter 2 (SGLT2) inhibitors are novel agents used to treat type 2 diabetic patients. We investigated the efficacy of the SGLT2 inhibitor ipragliflozin on diabetic nephropathy in Japanese patients with type 2 diabetes. Methods A 50 mg dose of ipragliflozin was administered for 24 weeks to 50 patients with type 2 diabetes who were concomitantly managed with diet and exercise therapy alone or antidiabetic medications other than SGLT2 inhibitors. Results At the end of the 24-week ipragliflozin treatment, significant decreases in mean glycated hemoglobin (HbA1c) (1.0±1.2%) and body weight (2.7 ± 2.5 kg) were observed; in addition, median urinary albumin-to-creatinine ratio (UACR) significantly decreased from 15.5 (8.0 - 85.7) to 12.9 (7.4 - 36.3) mg/gCr. Sub-analysis by renal function at baseline revealed that median UACR in patients with estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m2 decreased significantly from 12.3 (7.5 - 89.6) to 10.6 (5.8 - 27.3) mg/gCr. Furthermore, mean eGFR decreased significantly from 102.4 ± 8.6 to 93.6 ± 10.5 mL/min/1.73 m2 in these patients. In contrast, UACR and eGFR did not change significantly in patients with eGFR < 90. In addition, analysis of the relationship between the amount of change in UACR and blood pressure at 24 weeks revealed a significant positive correlation between UACR and SBP values, independently of the presence of diabetic nephropathy. Conclusions Our results indicate that ipragliflozin may facilitate HbA1c control and body weight reduction. Furthermore, our results also raise the possibility that ipragliflozin significantly reduces urinary albumin levels and improves glomerular hyperfiltration in a subset of patients with type 2 diabetes. PMID:28090231

  4. Effect of open-label infusion of an apoA-I-containing particle (CER-001) on RCT and artery wall thickness in patients with FHA

    NARCIS (Netherlands)

    Kootte, Ruud S.; Smits, Loek P.; van der Valk, Fleur M.; Dasseux, Jean-Louis; Keyserling, Constance H.; Barbaras, Ronald; Paolini, John F.; Santos, Raul D.; van Dijk, Theo H.; Dallinga-van Thie, Geesje M.; Nederveen, Aart J.; Mulder, Willem J. M.; Hovingh, G. Kees; Kastelein, John J. P.; Groen, Albert K.; Stroes, Erik S.

    2015-01-01

    Reverse cholesterol transport (RCT) contributes to the anti-atherogenic effects of HDL. Patients with the orphan disease, familial hypoalphalipoproteinemia (FHA), are characterized by decreased tissue cholesterol removal and an increased atherogenic burden. We performed an open-label uncontrolled pr

  5. Efficacy of Atomoxetine for the Treatment of ADHD Symptoms in Patients with Pervasive Developmental Disorders: A Prospective, Open-Label Study

    Science.gov (United States)

    Fernandez-Jaen, Alberto; Fernandez-Mayoralas, Daniel Martin; Calleja-Perez, Beatriz; Munoz-Jareno, Nuria; Campos Diaz, Maria del Rosario; Lopez-Arribas, Sonia

    2013-01-01

    Objective: Atomoxetine's tolerance and efficacy were studied in 24 patients with pervasive developmental disorder and symptoms of ADHD. Method: Prospective, open-label, 16-week study was performed, using the variables of the Clinical Global Impression Scale and the Conners' Scale, among others. Results: A significant difference was found between…

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

    NARCIS (Netherlands)

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

    2007-01-01

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

  7. 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…

  8. 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

    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......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...

  9. An Open-Label Pilot Study to Assess the Efficacy and Safety of Virgin Coconut Oil in Reducing Visceral Adiposity

    Science.gov (United States)

    Liau, Kai Ming; Lee, Yeong Yeh; Chen, Chee Keong; Rasool, Aida Hanum G.

    2011-01-01

    Introduction. This is an open-label pilot study on four weeks of virgin coconut oil (VCO) to investigate its efficacy in weight reduction and its safety of use in 20 obese but healthy Malay volunteers. Methodology. Efficacy was assessed by measuring weight and associated anthropometric parameters and lipid profile one week before and one week after VCO intake. Safety was assessed by comparing organ function tests one week before and one week after intake of VCO. Paired t-test was used to analyse any differences in all the measurable variables. Results. Only waist circumference (WC) was significantly reduced with a mean reduction of 2.86 cm or 0.97% from initial measurement (P = .02). WC reduction was only seen in males (P < .05). There was no change in the lipid profile. There was a small reduction in creatinine and alanine transferase levels. Conclusion. VCO is efficacious for WC reduction especially in males and it is safe for use in humans. PMID:22164340

  10. Onabotulinumtoxin A Treatment of Drooling in Children with Cerebral Palsy: A Prospective, Longitudinal Open-Label Study

    DEFF Research Database (Denmark)

    Møller, Eigild; Pedersen, Søren Anker; Vinicoff, Pablo Gustavo;

    2015-01-01

    The aim of this prospective open-label study was to treat disabling drooling in children with cerebral palsy (CP) with onabotulinumtoxin A (A/Ona, Botox®) into submandibular and parotid glands and find the lowest effective dosage and least invasive method. A/Ona was injected in 14 children, Mean...... age 9 years, SD 3 years, under ultrasonic guidance in six successive Series, with at least six months between injections. Doses and gland involvement increased from Series A to F (units (U) per submandibular/parotid gland: A, 10/0; B, 15/0; C, 20/0; D, 20/20; E, 30/20; and F, 30/30). The effect...... in E and F, but with swallowing problems ≤5 weeks in 3 of 28 treatments. F had largest VAS and UWS reduction (64% and 49%). We recommend: Start with dose D A/Ona (both submandibular and parotid glands and a total of 80 U) and increase to E and eventually F (total 120 U) without sufficient response....

  11. Efficacy of Folic Acid Supplementation in Autistic Children Participating in Structured Teaching: An Open-Label Trial.

    Science.gov (United States)

    Sun, Caihong; Zou, Mingyang; Zhao, Dong; Xia, Wei; Wu, Lijie

    2016-06-07

    Autism spectrum disorders (ASD) are recognized as a major public health issue. Here, we evaluated the effects of folic acid intervention on methylation cycles and oxidative stress in autistic children enrolled in structured teaching. Sixty-six autistic children enrolled in this open-label trial and participated in three months of structured teaching. Forty-four children were treated with 400 μg folic acid (two times/daily) for a period of three months during their structured teaching (intervention group), while the remaining 22 children were not given any supplement for the duration of the study (control group). The Autism Treatment Evaluation Checklist (ATEC) and Psychoeducational Profile-third edition (PEP-3) were measured at the beginning and end of the treatment period. Folic acid, homocysteine, and glutathione metabolism in plasma were measured before and after treatment in 29 autistic children randomly selected from the intervention group and were compared with 29 age-matched unaffected children (typical developmental group). The results illustrated folic acid intervention improved autism symptoms towards sociability, cognitive verbal/preverbal, receptive language, and affective expression and communication. Furthermore, this treatment also improved the concentrations of folic acid, homocysteine, and normalized glutathione redox metabolism. Folic acid supplementation may have a certain role in the treatment of children with autism.

  12. Efficacy of Folic Acid Supplementation in Autistic Children Participating in Structured Teaching: An Open-Label Trial

    Directory of Open Access Journals (Sweden)

    Caihong Sun

    2016-06-01

    Full Text Available Autism spectrum disorders (ASD are recognized as a major public health issue. Here, we evaluated the effects of folic acid intervention on methylation cycles and oxidative stress in autistic children enrolled in structured teaching. Sixty-six autistic children enrolled in this open-label trial and participated in three months of structured teaching. Forty-four children were treated with 400 μg folic acid (two times/daily for a period of three months during their structured teaching (intervention group, while the remaining 22 children were not given any supplement for the duration of the study (control group. The Autism Treatment Evaluation Checklist (ATEC and Psychoeducational Profile-third edition (PEP-3 were measured at the beginning and end of the treatment period. Folic acid, homocysteine, and glutathione metabolism in plasma were measured before and after treatment in 29 autistic children randomly selected from the intervention group and were compared with 29 age-matched unaffected children (typical developmental group. The results illustrated folic acid intervention improved autism symptoms towards sociability, cognitive verbal/preverbal, receptive language, and affective expression and communication. Furthermore, this treatment also improved the concentrations of folic acid, homocysteine, and normalized glutathione redox metabolism. Folic acid supplementation may have a certain role in the treatment of children with autism.

  13. Treprostinil sodium (Remodulin), a prostacyclin analog, in the treatment of critical limb ischemia: open-label study.

    Science.gov (United States)

    Berman, Scott; Quick, Rhonda; Yoder, Pam; Voigt, Sonia; Strootman, Deborah; Wade, Michael

    2006-01-01

    The purpose of this study was to assess the safety of continuous subcutaneous therapy with treprostinil sodium (Remodulin), a prostacyclin analog, and its effect on ischemic rest pain and ischemic wound healing in subjects with critical limb ischemia (CLI) and no planned revascularization procedure. This was a 12-week, open-label, single-center pilot study enrolling 10 subjects (mean age 82.4 years) with Fontaine stage III to IV (Rutherford class 4-6) peripheral arterial disease and ankle brachial indices less than 0.55. The primary end point was safety, and the secondary end points were the effects of treatment on ischemic rest pain, limb salvage, and wound healing. There was a 62% reduction in mean worst rest pain and a 57% reduction in mean average rest pain at week 12, with most subjects using less pain medication. Three subjects experienced complete healing of their wounds. No subject developed a new wound during the trial. Treprostinil was generally well tolerated. Subcutaneous infusion-site pain was the most frequently reported side effect, with one subject withdrawing from the study as a result. Jaw pain was reported by two subjects. One subject experienced two serious adverse events considered unrelated to treprostinil (cholecystitis and congestive heart failure). This study demonstrates that chronic, continuous subcutaneous treprostinil is safe and can be useful in the treatment of ischemic pain and wounds in subjects with CLI. Future controlled studies are needed to evaluate these effects and determine appropriate patient selection.

  14. Effect of topical vitamin D on chronic kidney disease-associated pruritus: An open-label pilot study.

    Science.gov (United States)

    Jung, Kyung Eun; Woo, Yu Ri; Lee, Joong Sun; Shin, Jong Ho; Jeong, Jin Uk; Koo, Dae Won; Bang, Ki Tae

    2015-08-01

    Chronic kidney disease-associated pruritus (CKD-aP) is a troublesome symptom in patients with end-stage renal disease (ESRD). Recently, vitamin D deficiency has been known to be one of the possible etiologic factors in CKD-aP. However, limited data is available on whether topical vitamin D treatment is effective for relieving CKD-aP. Therefore, the purpose of this study is to evaluate the effectiveness of topically vitamin D for CKD-aP. Twenty-three patients with CKD-aP were enrolled in a single center, open-label study. Patients were instructed to apply a topical vitamin D (calcipotriol) agent (Daivonex solution; LEO Pharma) or vehicle solution twice daily for a month. We assessed the efficacy and safety of topical vitamin D on CKD-aP using clinical and dermoscopic photographs, and questionnaires including the validated modified pruritus assessment score (VMPAS) and visual analog scale (VAS) every 2 weeks. Dry dermoscopic findings showed significant improvement of scale (dryness) on the skin of topical vitamin D-treated patients compared with those of the vehicle group. Both VMPAS and VAS were significantly decreased after 2 and 4 weeks of the topical vitamin D treatment compared with the vehicle, respectively (P < 0.05). No significant side-effects were observed. Topical vitamin D may be one of the safe and effective therapeutic candidates for CKD-aP.

  15. 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.

  16. 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.

  17. Reduction of tinnitus severity by the centrally acting muscle relaxant cyclobenzaprine: an open-label pilot study.

    Science.gov (United States)

    Coelho, Claudia; Figueiredo, Ricardo; Frank, Elmar; Burger, Julia; Schecklmann, Martin; Landgrebe, Michael; Langguth, Berthold; Elgoyhen, Ana Belen

    2012-01-01

    Tinnitus, the phantom perception of sounds, is a highly prevalent disorder. Although a wide variety of drugs have been investigated off label for the treatment of tinnitus, there is no approved pharmacotherapy. We report an open-label exploratory pilot study to assess the effect of muscle relaxants acting on the central nervous system on tinnitus patients. Cyclobenzaprine at high (30 mg) and low doses (10 mg), orphenadrine (100 mg), tizanidine (24 mg) and eperisone (50 mg) were administered to a maximum of 20 patients per group over a 12-week period. High-dose cyclobenzaprine resulted in a significant reduction in the Tinnitus Handicap Inventory (THI) score between baseline and week 12 in the intention-to-treat sample. On the other hand, other treatments were not effective. These results were confirmed in an explorative analysis where baseline corrected THI and Clinical Global Impression scores at week 12 were compared between groups. The present open trial presents a new promising pharmacotherapy for tinnitus that should be validated in placebo-controlled double-blind trials.

  18. 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.

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

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    Chiu Nan-Ying

    2010-09-01

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

  20. An open-label study of algorithm-based treatment versus treatment-as-usual for patients with schizophrenia

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    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. Sertraline and rapid eye movement sleep without atonia: an 8-week, open-label study of depressed patients.

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    Zhang, Bin; Hao, Yanli; Jia, Fujun; Tang, Yi; Li, Xueli; Liu, Wuhan; Arnulf, Isabelle

    2013-12-02

    Previous studies have reported that selective serotonin reuptake inhibitors (SSRIs) may induce or exacerbate rapid eye movement (REM) sleep without atonia (RSWA) and increase the risk of developing REM sleep behavior disorder (RBD). However, most of these studies are retrospective and cross-sectional and employed small sample sizes and a mixture of SSRIs. In this 8-week open-label trial of sertraline in depressed patients (n = 31), depressed patients were administered 50mg sertraline at 8 am on the 1st day and subsequently titrated up to a maximum of 200mg/day. All patients underwent repeated video-polysomnography (vPSG) (baseline, 1st day, 14th day, 28th day, and 56th day). Both tonic (submental) and phasic (submental and anterior tibialis) RSWA events were visually counted. Tonic RSWA increased from 3.2 ± 1.8% at baseline to 5.1 ± 2.3% on the 1st day and 10.4 ± 2.7% on the 14th day; after that, measurements were stable until the 56th day. A similar profile was observed for phasic RSWA. The increases in tonic RSWA (r = 0.56, P = 0.004) and phasic RSWA (submental: r = -0.51, P = 0.02; anterior tibialis: r = 0.41, P = 0.04) were correlated with the degree of the prolonging of REM latency. All of RSWAs were not correlated with patients' demographic and clinical characteristics. Sertraline may induce or exacerbate RSWA. In contrast to idiopathic RBD, sertraline-related RSWA had the specific characteristics of being correlated with the degree of the prolonging of REM latency and no predominance of male sex and elder age, suggesting different pathophysiological mechanisms. The antidepressant-related RSWA should be a potential public health problem in the depressed patients.

  2. Eldecalcitol improves muscle strength and dynamic balance in postmenopausal women with osteoporosis: an open-label randomized controlled study.

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    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.

  3. Agomelatine versus Sertraline: An Observational, Open-labeled and 12 Weeks Follow-up Study on Efficacy and Tolerability

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    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

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

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    Hardoy Maria

    2006-08-01

    Full Text Available Abstract Background Atypical antipsychotics are widely used in the treatment of bipolar disorders. Amisulpride is an atypical antipsychotic that has been proven to be effective in treatment of schizophrenia, major depressive disorder and, more recently, acute mania. At the moment, however, no study has assessed the effectiveness of this compound in maintenance therapy of bipolar disorders. The purpose of this study was to assess the long-term effectiveness of amisulpride in combination with standard treatments in patients with bipolar I disorder who have shown inadequate responses to ongoing standard therapies. Methods The study enrolled fourteen bipolar I outpatients, not responding to ongoing standard therapy. Three patients discontinued treatment but 11 were followed-up for 11.7 ± 8.2 months before (range 3–24 months and 5.2 ± 2.7 months after the introduction of amisulpride (range 3–9 months. Relapse rates before and during treatment with amisulpride were calculated in accordance to an increase of 1 or more in Clinical Global Impressions Scale-Bipolar Version (CGI-BP score that was accompanied by a change in therapy or to an exacerbation of the symptoms that required hospitalization. Results A statistically significant decrease in overall relapse rate was observed during the period of amisulpride therapy compared with months previous to the introduction of amisulpride. The relative risk of relapse in the absence of amisulpride therapy was 3.1 (χ2 = 4.2, P Discussion and conclusion This open-label study suggests that long-term therapy with amisulpride may benefit patients by improving global symptoms of bipolar disorder and reducing the rate of manic/mixed relapses. Large, randomized, double-blind, placebo-controlled studies are needed to explore the benefits of adding long-term amisulpride to standard therapies for bipolar disorder.

  5. An open-label study of anidulafungin for the treatment of candidaemia/invasive candidiasis in Latin America.

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    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.

  6. Combined gemcitabine and S-1 chemotherapy for treating unresectable hilar cholangiocarcinoma: a randomized open-label clinical trial.

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    Li, Hao; Zhang, Zheng-Yun; Zhou, Zun-Qiang; Guan, Jiao; Tong, Da-Nian; Zhou, Guang-Wen

    2016-05-03

    Although the combination of cisplatin and gemcitabine (GEM) is considered the standard first-line chemotherapy against unresectable hilar cholangiocarcinoma (HC), its efficacy is discouraging. The present randomized open-label clinical trial aimed to evaluate the efficacy and safety of the GEM plus S-1 (GEM-S-1) combination against unresectable HC. Twenty-five patients per group were randomly assigned to receive GEM, S-1 or GEM-S-1. Neutropenia (56%) and leukopenia (40%) were the most common chemotherapy-related toxicities in the GEM-S-1 group. Median overall survival (OS) in the GEM-S-1, GEM and S-1 groups was 11, 10 and 6 months, respectively. GEM plus S-1 significantly improved OS compared to S-1 monotherapy (OR=0.68; 95%CI, 0.50-0.90; P=0.008). Median progression-free survival (PFS) times in the GEM-S-1, GEM and S-1 groups were 4.90, 3.70 and 1.60 months, respectively. GEM plus S-1 significantly improved PFS compared to S-1 monotherapy (OR=0.50; 95%CI, 0.27-0.91; P=0.024). Response rates were 36%, 24% and 8% in the GEM-S-1, GEM and S-1 groups, respectively. A statistically significant difference was found in response rates between the gemcitabine-S-1 and S-1 groups (36% vs 8%, P=0.017). Patients with CA19-9S-1 provides a better OS, PFS and response rate than S-1 monotherapy, but it did not significantly differ from GEM monotherapy. (ChiCTR-TRC-14004733).

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

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    Gobbi G

    2014-05-01

    Full Text Available Gabriella Gobbi,1,2 Stefano Comai,1 Guy Debonnel1,2,† 1Neurobiological Psychiatric Unit, Department of Psychiatry, McGill University and McGill University Health Center, 2Institut Philippe Pinel, Department of Psychiatry, Université de Montréal, Montréal, QC, Canada †Guy Debonnel passed away on November 4, 2006 Objective: Patients suffering from psychosis are more likely than the general population to commit aggressive acts, but the therapeutics of aggressive behavior are still a matter of debate. Methods: This pilot randomized, open-label study compared the efficacy of quetiapine versus olanzapine in reducing impulsive and aggressive behaviors (primary endpoints and psychotic symptoms (secondary endpoints from baseline to days 1, 7, 14, 28, 42, 56, and 70, in 15 violent schizophrenic patients hospitalized in a maximum-security psychiatric hospital. Results: Quetiapine (525±45 mg and olanzapine (18.5±4.8 mg were both efficacious in reducing Impulsivity Rating Scale from baseline to day 70. In addition, both treatments reduced the Brief Psychiatric Rating Scale, Positive and Negative Syndrome Scale, and Clinical Global Impression Scale scores at day 70 compared to baseline, and no differences were observed between treatments. Moreover, quetiapine, but not olanzapine, yielded an improvement of depressive symptoms in the items “depression” in Brief Psychiatric Rating Scale and “blunted affect” in Positive and Negative Syndrome Scale. Modified Overt Aggression Scale scores were also decreased from baseline to the endpoint, but due to the limited number of patients, it was not possible to detect a significant difference. Conclusion: In this pilot study, quetiapine and olanzapine equally decreased impulsive and psychotic symptoms after 8 weeks of treatment. Double-blind, large studies are needed to confirm the validity of these two treatments in highly aggressive and violent schizophrenic patients. Keywords: schizophrenia, aggression

  8. A randomised, open-label, comparative study of tranexamic acid microinjections and tranexamic acid with microneedling in patients with melasma

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    Leelavathy Budamakuntla

    2013-01-01

    Full Text Available Background: Melasma is a common cause of facial hyperpigmentation with significant cosmetic deformity. Although several treatment modalities are available, none is satisfactory. Aim: To compare the therapeutic efficacy and safety of tranexamic acid (TA microinjections versus tranexamic acid with microneedling in melasma. Materials and Methods: This is a prospective, randomised, open-label study with a sample size of 60; 30 in each treatment arms. Thirty patients were administered with localised microinjections of TA in one arm, and other 30 with TA with microneedling. The procedure was done at monthly intervals (0, 4 and 8 weeks and followed up for three consecutive months. Clinical images were taken at each visit including modified Melasma Area Severity Index MASI scoring, patient global assessment and physician global assessment to assess the clinical response. Results: In the microinjection group, there was 35.72% improvement in the MASI score compared to 44.41% in the microneedling group, at the end of third follow-up visit. Six patients (26.09% in the microinjections group, as compared to 12 patients (41.38% in the microneedling group, showed more than 50% improvement. However, there were no major adverse events observed in both the treatment groups. Conclusions: On the basis of these results, TA can be used as potentially a new, effective, safe and promising therapeutic agent in melasma. The medication is easily available and affordable. Better therapeutic response to treatment in the microneedling group could be attributed to the deeper and uniform delivery of the medication through microchannels created by microneedling.

  9. A Randomised, Open-label, Comparative Study of Tranexamic Acid Microinjections and Tranexamic Acid with Microneedling in Patients with Melasma

    Science.gov (United States)

    Budamakuntla, Leelavathy; Loganathan, Eswari; Suresh, Deepak Hurkudli; Shanmugam, Sharavana; Suryanarayan, Shwetha; Dongare, Aparna; Venkataramiah, Lakshmi Dammaningala; Prabhu, Namitha

    2013-01-01

    Background: Melasma is a common cause of facial hyperpigmentation with significant cosmetic deformity. Although several treatment modalities are available, none is satisfactory. Aim: To compare the therapeutic efficacy and safety of tranexamic acid (TA) microinjections versus tranexamic acid with microneedling in melasma. Materials and Methods: This is a prospective, randomised, open-label study with a sample size of 60; 30 in each treatment arms. Thirty patients were administered with localised microinjections of TA in one arm, and other 30 with TA with microneedling. The procedure was done at monthly intervals (0, 4 and 8 weeks) and followed up for three consecutive months. Clinical images were taken at each visit including modified Melasma Area Severity Index MASI scoring, patient global assessment and physician global assessment to assess the clinical response. Results: In the microinjection group, there was 35.72% improvement in the MASI score compared to 44.41% in the microneedling group, at the end of third follow-up visit. Six patients (26.09%) in the microinjections group, as compared to 12 patients (41.38%) in the microneedling group, showed more than 50% improvement. However, there were no major adverse events observed in both the treatment groups. Conclusions: On the basis of these results, TA can be used as potentially a new, effective, safe and promising therapeutic agent in melasma. The medication is easily available and affordable. Better therapeutic response to treatment in the microneedling group could be attributed to the deeper and uniform delivery of the medication through microchannels created by microneedling. PMID:24163529

  10. Gatifloxacin versus ofloxacin for the treatment of uncomplicated enteric fever in Nepal: an open-label, randomized, controlled trial.

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    Samir Koirala

    Full Text Available BACKGROUND: Fluoroquinolones are the most commonly used group of antimicrobials for the treatment of enteric fever, but no direct comparison between two fluoroquinolones has been performed in a large randomised trial. An open-label randomized trial was conducted to investigate whether gatifloxacin is more effective than ofloxacin in the treatment of uncomplicated enteric fever caused by nalidixic acid-resistant Salmonella enterica serovars Typhi and Paratyphi A. METHODOLOGY AND PRINCIPAL FINDINGS: Adults and children clinically diagnosed with uncomplicated enteric fever were enrolled in the study to receive gatifloxacin (10 mg/kg/day in a single dose or ofloxacin (20 mg/kg/day in two divided doses for 7 days. Patients were followed for six months. The primary outcome was treatment failure in patients infected with nalidixic acid resistant isolates. 627 patients with a median age of 17 (IQR 9-23 years were randomised. Of the 218 patients with culture confirmed enteric fever, 170 patients were infected with nalidixic acid-resistant isolates. In the ofloxacin group, 6 out of 83 patients had treatment failure compared to 5 out of 87 in the gatifloxacin group (hazard ratio [HR] of time to failure 0.81, 95% CI 0.25 to 2.65, p = 0.73. The median time to fever clearance was 4.70 days (IQR 2.98-5.90 in the ofloxacin group versus 3.31 days (IQR 2.29-4.75 in the gatifloxacin group (HR = 1.59, 95% CI 1.16 to 2.18, p = 0.004. The results in all blood culture-confirmed patients and all randomized patients were comparable. CONCLUSION: Gatifloxacin was not superior to ofloxacin in preventing failure, but use of gatifloxacin did result in more prompt fever clearance time compared to ofloxacin. TRIAL REGISTRATION: ISRCTN 63006567 (www.controlled-trials.com.

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

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    Bellasi Antonio

    2016-04-01

    Full Text Available Whether anemia and mineral bone abnormalities (chronic kidney disease–mineral bone disorder [CKD-MBD] are associated still remains to be elucidated. Both anemia and CKD-MBD have been associated with adverse cardiovascular outcome and poor quality of life. However, recent evidence suggests that use of large doses of erythropoietin-stimulating agents (ESAs to correct hemoglobin (Hb may be detrimental in CKD. The Optimal Anemia Treatment in End Stage Renal Disease (ESRD (Optimal ESRD Treatment study will assess whether lowering of parathyroid hormone (PTH is associated with a reduction in ESA consumption. The Optimal ESRD Treatment study is a pilot single-center open-label study with blinded end point (a prospective randomized open blinded end-point [PROBE] design enrolling 50 patients on maintenance dialysis. Eligible patients with intact PTH (iPTH 300-540 pg/mL and Hb 10-11.5 g/dL will be randomized 1:1 to strict PTH control (150-300 pg/mL versus standard care (PTH range 300-540 pg/mL. Available drugs for CKD-MBD and anemia treatment will be managed by the attending physician to maintain the desired levels of PTH (according to study arm allocation and Hb (10-11.5 g/dL. Echocardiographic data for cardiac structure and function as well as arterial stiffness will be assessed at study inception and completion. The Optimal ESRD Treatment study should shed light on the complicated interplay of anemia and CKD-MBD and on the feasibility of clinical trials in this domain. The study results are expected in the spring of 2017.

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

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    Sparavigna A

    2014-10-01

    Full Text Available Adele Sparavigna, Beatrice Tenconi, Ileana De Ponti Derming Srl, Monza, Italy Background: Rosacea is a common, incurable skin barrier disorder characterized by relapses and remissions. Purpose: To evaluate the efficacy of Farmaka Rosacea Cream (FRC, a novel topical formulation for rosacea. Methods: This single-center, open-label pilot study comprised a single-dose substudy in 20 healthy subjects and a long-term, repeat-dose substudy in 22 subjects with rosacea. The 2-hour, controlled, single-dose substudy assessed the soothing and reepithelialization properties of FRC after stripping-induced erythema based on the erythema index, transepidermal water loss, skin hydration, and clinical assessments of erythema. In the long-term substudy, subjects applied FRC twice daily for 8 weeks. Clinical assessments included vascular and pigmentary homogeneity and erythema and hemoglobin indices. Subjects completed questionnaires to assess FRC efficacy and cosmetic acceptability. Results: Greater reductions were seen in FRC-treated areas compared with untreated areas for the erythema index (-16% versus -8%; P<0.001 and mean transepidermal water loss (-35.8% versus -10.1%; P<0.001 30 minutes after stripping. Significant improvements over untreated areas were maintained 2 hours after stripping. Skin hydration and clinical erythema assessments also indicated that FRC soothed rosacea symptoms and promoted skin reepithelialization. Erythema and hemoglobin indices were significantly reduced from baseline after 4 and 8 weeks of treatment. Clinically assessed parameters were significantly improved following FRC application. Subjects assessed FRC positively. Conclusion: Improvement of rosacea symptoms was noted with FRC application. The main film-forming ingredients of FRC (trehalose, cholesterol, ceramide, and fatty acids, combined with other soothing and calming ingredients and ultraviolet filters, could explain its efficacy. Keywords: rosacea, erythema, skin

  13. Treatment of distal subungual onychomycosis with a topical preparation of urea, propylene glycol and lactic acid: results of a 24-week, double-blind, placebo-controlled study.

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    Emtestam, L; Kaaman, T; Rensfeldt, K

    2012-11-01

    Onychomycosis is difficult to cure as this requires eradication of the primary infection and protection of new areas of growth from reinfection. A new topical treatment (K101) has been developed. The aim of this study was to assess the efficacy, safety and tolerability of K101 treatment of distal subungual onychomycosis. This was a 24-week (plus 2-week washout), multicentre, randomised, double-blind, placebo-controlled study in 493 patients with distal subungual onychomycosis (K101, n = 346; placebo, n = 147), stratified according to degree of nail involvement. More patients with ≤50% nail involvement achieved the primary endpoint (mycological cure after 26 weeks) in the K101 group (27.2%) than placebo (10.4%; P = 0.0012). Proportions for patients with 51-75% involvement were 19.1% for K101 and 7.0% for placebo (not significant). More patients applying K101 than placebo judged that their condition had improved from week 2 (P = 0.0148) to week 24 (P = 0.0004). No safety issues were identified. K101 provides early visible improvements in nail appearance and a clinically meaningful antifungal activity.

  14. 24-Week Exposure to Oxidized Tyrosine Induces Hepatic Fibrosis Involving Activation of the MAPK/TGF-β1 Signaling Pathway in Sprague-Dawley Rats Model

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    Zhuqing Leslie Li

    2016-01-01

    Full Text Available Scope. Oxidized tyrosine (O-Tyr has been widely detected in many consumer protein products. O-Tyr products such as dityrosine (Dityr and 3-nitrotyrosine (3-NT are universal biomarkers of protein oxidation and have been demonstrated to be associated with metabolic disorders in biological system. Evaluation of potential intracorporal effects of dietary O-Tyr is important since the mechanism of biological impacts induced by oral oxidized protein products (OPPs is still limited although we have proved that some dietary OPPs would induce oxidative injury to liver and kidney. Methods and Results. The present study aimed to investigate the dose-dependent hepatic injury caused by oral O-Tyr in rats. 24-week feeding of O-Tyr enhanced aspartate aminotransferase (AST and alanine aminotransferase (ALT activities, increased total bilirubin (TBiL content, and led to oxidative damage in rats liver. Besides, O-Tyr distinctly increased the phosphorylation of p38 and ERK2 MAPKs and enhanced fibrosis-related TGF-β1 and Smad2/3 levels. Higher extracellular matrix (ECM indexes (ICTP, PIIINP and histological examination (HE and Masson staining also supported dose-dependent hepatic fibrosis caused by O-Tyr. Conclusion. These findings reveal that O-Tyr may induce oxidative damage and hepatic fibrosis via MAPK/TGF-β1 signaling pathway, in which ROS together with malondialdehyde (MDA and OPPs act as the pivotal mediators.

  15. A Nutritional Formulation for Cognitive Performance in Mild Cognitive Impairment: A Placebo-Controlled Trial with an Open-Label Extension.

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    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.

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

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    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

  17. A Prospective, Open Label, Observational Study to Assess the Safety and Efficacy of Herbal Cough Syrup Mykoff® in Patients Suffering from Cough of Varied Aetiologies

    OpenAIRE

    Mangesh Bhalerao; Pradip Awale; Abhijeet Sawle; Dhananjay Sangle; Devendra B Sonawane; Vilas Chavan

    2013-01-01

    A prospective, open label, observational study was conducted at general outpatient clinic to assess the safety and efficacy of herbal cough syrup Mykoff® in patients suffering from cough of varied aetiologies. The patients of either sex, age > 3yrs, suffering from cough due to common cold, mild to moderate upper respiratory tract infections, allergic cough and smoker’s cough were enrolled. The safety was evaluated by means of an analysis of adverse events. In addition, efficacy and tolerabili...

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

    OpenAIRE

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

    2015-01-01

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

  19. A randomized, open-label trial of iron isomaltoside 1000 (Monofer®) compared with iron sucrose (Venofer®) as maintenance therapy in haemodialysis patients

    OpenAIRE

    Bhandari, Sunil; Kalra, Philip A.; Kothari, Jatin; Ambühl, Patrice M.; Christensen, Jeppe H.; Essaian, Ashot M.; Thomsen, Lars L.; Macdougall, Iain C.; Coyne, Daniel W.

    2015-01-01

    Background Iron deficiency anaemia is common in patients with chronic kidney disease, and intravenous iron is the preferred treatment for those on haemodialysis. The aim of this trial was to compare the efficacy and safety of iron isomaltoside 1000 (Monofer®) with iron sucrose (Venofer®) in haemodialysis patients. Methods This was an open-label, randomized, multicentre, non-inferiority trial conducted in 351 haemodialysis subjects randomized 2 : 1 to either iron isomaltoside 1000 (Group A) or...

  20. Ringer’s lactate, but not hydroxyethyl starch, prolongs the food intolerance time after major abdominal surgery; an open-labelled clinical trial

    OpenAIRE

    Li, Yuhong; He, Rui; Ying, Xiaojiang; Hahn, Robert

    2015-01-01

    Background: The infusion of large amounts of Ringers lactate prolongs the functional gastrointestinal recovery time and increases the number of complications after open abdominal surgery. We performed an open-labelled clinical trial to determine whether hydroxyethyl starch or Ringers lactate exerts these adverse effects when the surgery is performed by laparoscopy. Methods: Eighty-eight patients scheduled for major abdominal cancer surgery (83% by laparoscopy) received a first-line fluid trea...

  1. Evaluation of efficacy and tolerability of eperisone and thiocolchicoside in treatment of low back pain associated with muscle spasm: An open label, prospective, randomized controlled trial

    OpenAIRE

    Syed H. Maaz; Prakash N. Khandelwal; Shiraz M. Baig; Sudhakar M. Doifode; Ulhas M. Ghotkar

    2016-01-01

    Background: Low back pain has a high prevalence in adult population. Because of reflex muscle spasm, muscle relaxants are frequently used either alone or in combination with analgesics. Eperisone inhibits voltage gated sodium channels in brain stem and Thiocolchicoside acts via GABA-mediated mechanism to relax muscle spasm and relieves pain. Methods: This was a prospective; open labeled, randomized, two-arm, parallel group, controlled, clinical trial. 113 patients were randomised to two gr...

  2. Metformin Treatment in Type 2 Diabetes in Pregnancy: An Active Controlled, Parallel-Group, Randomized, Open Label Study in Patients with Type 2 Diabetes in Pregnancy

    OpenAIRE

    2015-01-01

    Aims. To assess the effect of metformin and to compare it with insulin treatment in patients with type 2 diabetes in pregnancy in terms of perinatal outcome, maternal complications, additional insulin requirement, and treatment acceptability. Methods. In this randomized, open label study, 206 patients with type 2 diabetes in pregnancy who met the eligibility criteria were selected from the antenatal clinics. Insulin was added to metformin treatment when required, to maintain the target glycem...

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. Comparison of Doxycycline, Minocycline, Doxycycline plus Albendazole and Albendazole Alone in Their Efficacy against Onchocerciasis in a Randomized, Open-Label, Pilot Trial

    Science.gov (United States)

    Batsa, Linda; Ayisi-Boateng, Nana Kwame; Osei-Mensah, Jubin; Mubarik, Yusif; Konadu, Peter; Ricchiuto, Arcangelo; Fimmers, Rolf; Arriens, Sandra; Dubben, Bettina; Ford, Louise; Taylor, Mark; Hoerauf, Achim

    2017-01-01

    The search for new macrofilaricidal drugs against onchocerciasis that can be administered in shorter regimens than required for doxycycline (DOX, 200mg/d given for 4–6 weeks), identified minocycline (MIN) with superior efficacy to DOX. Further reduction in the treatment regimen may be achieved with co-administration with standard anti-filarial drugs. Therefore a randomized, open-label, pilot trial was carried out in an area in Ghana endemic for onchocerciasis, comprising 5 different regimens: the standard regimen DOX 200mg/d for 4 weeks (DOX 4w, N = 33), the experimental regimens MIN 200mg/d for 3 weeks (MIN 3w; N = 30), DOX 200mg/d for 3 weeks plus albendazole (ALB) 800mg/d for 3 days (DOX 3w + ALB 3d, N = 32), DOX 200mg/d for 3 weeks (DOX 3w, N = 31) and ALB 800mg for 3 days (ALB 3d, N = 30). Out of 158 randomized participants, 116 (74.4%) were present for the follow-up at 6 months of whom 99 participants (63.5%) followed the treatment per protocol and underwent surgery. Histological analysis of the adult worms in the extirpated nodules revealed absence of Wolbachia in 98.8% (DOX 4w), 81.4% (DOX 3w + ALB 3d), 72.7% (MIN 3w), 64.1% (DOX 3w) and 35.2% (ALB 3d) of the female worms. All 4 treatment regimens showed superiority to ALB 3d (p < 0.001, p < 0.001, p = 0.002, p = 0.008, respectively), which was confirmed by real-time PCR. Additionally, DOX 4w showed superiority to all other treatment arms. Furthermore DOX 4w and DOX 3w + ALB 3d showed a higher amount of female worms with degenerated embryogenesis compared to ALB 3d (p = 0.028, p = 0.042, respectively). These results confirm earlier studies that DOX 4w is sufficient for Wolbachia depletion and the desired parasitological effects. The data further suggest that there is an additive effect of ALB (3 days) on top of that of DOX alone, and that MIN shows a trend for stronger potency than DOX. These latter two results are preliminary and need confirmation in a fully randomized controlled phase 2 trial. Trial

  10. 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.

  11. Pharmacokinetic interaction between udenafil and dapoxetine: a randomized, open-labeled crossover study in healthy male volunteers

    Directory of Open Access Journals (Sweden)

    Kim YH

    2015-02-01

    Full Text Available Yo Han Kim,1 Hee Youn Choi,1 Shi Hyang Lee,1 Hae Sun Jeon,1 Hyeong-Seok Lim,1 Mi Young Bahng,2 Kyun-Seop Bae1 1Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, College of Medicine, University of Ulsan, 2Clinical Development Department, Dong-A ST Co, Ltd, Seoul, Republic of Korea Background: “Udenafil” is a phosphodiesterase-5 inhibitor indicated for erectile dysfunction. “Dapoxetine” is a serotonin transport inhibitor indicated for premature ejaculation. The aim of the study reported here was to investigate the pharmacokinetic drug interaction between udenafil and dapoxetine in healthy male subjects. Methods: An open-label, three-treatment, six-sequence, three-period crossover study was performed in healthy male subjects. In varying sequences, each subjects received single oral doses of udenafil 200 mg, dapoxetine 60 mg, and both treatments. The periods were separated by a washout period of 7 days. Serial blood samples were collected up to 48 hours after dosing. The plasma concentrations of udenafil and dapoxetine were determined using a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were obtained by non-compartmental analysis. Tolerability was assessed throughout the study. Results: Twenty-three healthy subjects completed the study. The geometric mean ratios of the area under the plasma concentration–time curve from time 0 to last measurable time point and measured peak plasma concentration for udenafil were 0.923 (90% confidence interval [CI]: 0.863–0.987 and 0.864 (90% CI: 0.789–0.947, respectively. The geometric mean ratios of the area under the plasma concentration–time curve from time 0 to last measurable time point and measured peak plasma concentration for dapoxetine were 1.125 (90% CI: 1.044–1.213 and 0.837 (90% CI: 0.758–0.925, respectively. There were no serious adverse events reported, and none of the subjects dropped out due to adverse events

  12. 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

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

    Directory of Open Access Journals (Sweden)

    Kasper S

    2017-03-01

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

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

    Science.gov (United States)

    Kasper, Siegfried; Dienel, Angelika

    2017-01-01

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

  15. Dexmedetomidine versus midazolam for conscious sedation in endoscopic retrograde cholangiopancreatography: An open-label randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Priyanka Sethi

    2014-01-01

    Full Text Available Background: Traditionally, midazolam has been used for providing conscious sedation in endoscopic retrograde cholangiopancreatography (ERCP. Recently, dexmedetomidine has been tried, but very little evidence exists to support its use. Objective: The primary objective was to compare haemodynamic, respiratory and recovery profile of both drugs. Secondary objective was to compare the degree of comfort experienced by patients and the usefulness of the drug to endoscopist. Study Design: Open-label Randomised Controlled Trial. Methods: Subjects between 18 and 60 years of age with American Society of Anaesthesiologist Grade I-II requiring ERCP were enrolled in two groups (30 each. Both groups received fentanyl 1 μg/kg IV at the beginning of ERCP. Group M received IV midazolam (0.04 mg/kg and additional 0.5 mg doses until Ramsay Sedation Scale (RSS score reached 3-4. Group D received dexmedetomidine at loading dose of 1 μg/kg over 10 min followed by 0.5 μg/kg/h infusion until RSS reached 3-4. The vital parameters (heart rate (HR, blood pressure (BP, respiration rate, SpO 2 , time to achieve RSS 3-4 and facial pain score (FPS were compared during and after the procedure. In the recovery room, time to reach modified Aldrete score (MAS 9-10 and patient and surgeon′s satisfaction scores was also recorded and compared. Any complication during or after the procedure were also noted. Results: In Group D, patients had lower HR and FPS at 5, 10 and 15 min following the initiation of sedation (P<0.05. There was no statistically significant difference in BP and respiratory rate. The procedure elicited a gag response in 29 (97% and 7 (23% subjects in Group M and Group D respectively (P<0.05. MAS of 9-10 at 5 min during recovery was achieved in 27 (90% subjects in Group D in contrast to 5 (17% in Group M (P<0.05. Dexmedetomidine showed higher patient and surgeon satisfaction scores (P<0.05. Conclusion: Dexmedetomidine can be a superior alternative to midazolam

  16. An Open-Label Study of an Herbal Topical Medication (QoolSkin for Patients with Chronic Plaque Psoriasis

    Directory of Open Access Journals (Sweden)

    Arnon D. Cohen

    2007-01-01

    Full Text Available QoolSkin is novel herbal topical medication indicated for the treatment of patients with psoriasis and we endeavored to determine the efficacy of QoolSkin in patients with chronic plaque psoriasis. In an open-label, parallel-group study conducted at four sites in Israel, patients with chronic plaque psoriasis were treated by application of QoolSkin two to three times per day, for a period of 16 weeks. Clinical assessment was performed using the Psoriasis Area and Severity Index (PASI and the Beer-Sheva Psoriasis Severity Score (BPSS. The study included 100 patients (48 men, 52 women; age 18–65 years. QoolSkin was well tolerated and there were no local or systemic side effects. There was a 19% reduction in PASI, from a mean of 9.8 ± 9.5 before treatment to 8.0 ± 9.6 after treatment (p = 0.09. There was a 20% reduction in BPSS, from a mean of 16.1 ± 9.8 before treatment to 12.8 ± 10.6 after treatment (p = 0.01. The reduction in PASI and BPSS was pronounced in women (32 and 31%, respectively as compared to men (9 and 11%, respectively. The reduction in PASI and BPSS was parallel to the length of time the patients were treated by QoolSkin. In patients treated by one of the investigators, who applied QoolSkin three times per day and for a long period of time (mean 101.1 days, the reduction in PASI was 32.0% and the reduction in BPSS was 37.8%. In patients with chronic plaque psoriasis, QoolSkin treatment was well tolerated. Application of QoolSkin was associated with a decrease in disease severity, as assessed by the patients and physicians. Application of QoolSkin three times per day for long period is associated with a better response to treatment.

  17. 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

  18. 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

  19. Effect of comorbid tics on a clinically meaningful response to 8-week open-label trial of fluoxetine in obsessive compulsive disorder.

    Science.gov (United States)

    Husted, David S; Shapira, Nathan A; Murphy, Tanya K; Mann, Giselle D; Ward, Herbert E; Goodman, Wayne K

    2007-01-01

    Currently, there are limited published data evaluating the effects of tics on serotonin reuptake inhibitor (SRI) monotherapy responses in treating obsessive-compulsive disorder (OCD). One retrospective case-controlled analysis of OCD patients treated with SRI monotherapy showed lesser improvement in OCD symptoms in patients with tics than those without. However, more recently there were preliminary reports of OCD subjects treated with SRI monotherapy which did not demonstrate poorer response in subjects with tics or Tourette's Syndrome (TS). The specific aim of this study was to investigate whether the presence of comorbid chronic tics affected "clinically meaningful improvement" [McDougle, C.J., Goodman, W.K., Leckman, J.F., Barr, L.C., Heninger, G.R., Price, L.H., 1993. The efficacy of fluvoxamine in obsessive-compulsive disorder: effects of comorbid chronic tic disorder. Journal of Clinical Psychopharmacology 13, 354-358] of OCD in an 8-week open-label trial of fluoxetine monotherapy. Seventy-four adult subjects (13 patients with comorbid chronic tics and 61 patients without tics) with a primary DSM-IV OCD diagnosis were treated with up to 40mg fluoxetine for 8 weeks and had at least one post-baseline evaluation. The results indicate that there was a significant response by time in both fluoxetine-with-tic subjects and fluoxetine-without-tic subjects. Additionally, there were 3 (23.0%) OCD subjects with tics who had clinically meaningful improvement versus 16 (26.2%) OCD subjects without tics that demonstrated similar levels of improvement. These findings indicate that OCD patients with or without chronic tic disorders did not have a differential response to an 8-week open-label trial of fluoxetine. Limitations include the relatively low number of tic subjects and the open-label nature of the study. Additional data are needed on how comorbid tics may affect SRI treatment response in OCD.

  20. Rotigotine transdermal system for long-term treatment of patients with advanced Parkinson's disease: results of two open-label extension studies, CLEOPATRA-PD and PREFER.

    Science.gov (United States)

    LeWitt, Peter A; Boroojerdi, Babak; Surmann, Erwin; Poewe, Werner

    2013-07-01

    Open-label extensions [studies SP516 (NCT00501969) and SP715 (NCT00594386)] of the CLEOPATRA-PD and PREFER studies were conducted to evaluate the safety, tolerability and efficacy of the dopaminergic agonist, rotigotine, over several years of follow-up in patients with advanced Parkinson's disease (PD). Eligible subjects completing the double-blind trials received open-label adjunctive rotigotine (≤16 mg/24 h) for up to 4 and 6 years in Studies SP516 and SP715, respectively. Safety and tolerability were assessed using adverse events, vital signs and laboratory parameters, and efficacy assessed using the unified Parkinson's disease rating scale (UPDRS). Of the 395 and 258 patients enrolled in the SP516 and SP715 studies, 48 and 45 % completed, respectively. Adverse events were typically dopaminergic effects [e.g., somnolence (18-25 %/patient-year), insomnia (5-7 %/patient-year), dyskinesias (4-8 %/patient-year) and hallucinations (4-8 %/patient-year)], or related to the transdermal application of a patch (application site reactions: 14-15 %/patient-year). There were no clinically relevant changes in vital signs or laboratory parameters in either study. Mean UPDRS part II (activities of daily living) and part III (motor function) total scores improved from double-blind baseline during dose titration, then gradually declined over the maintenance period. In study SP516, mean UPDRS part II and III total scores were 0.8 points above and 2.8 points below double-blind baseline, respectively, at end of treatment. In study SP715, mean UPDRS part II and III total scores were 4.1 points above and 0.2 points below baseline, respectively, at end of treatment. In these open-label studies, adjunctive rotigotine was efficacious with an acceptable safety and tolerability profile in patients with advanced PD for up to 6 years.

  1. Clinical Efficacy Comparison of Saccharomyces boulardii and Yogurt Fluid in Acute Non-Bloody Diarrhea in Children: A Randomized, Controlled, Open Label Study

    OpenAIRE

    Makbule EREN; Dinleyici, Ener C; Vandenplas,Yvan

    2010-01-01

    The purpose of this trial is to evaluate the clinical efficacy and cost/effectiveness of Saccharomyces boulardii compared with yogurt fluid (YF) in acute non-bloody diarrhea in children. This randomized, prospective open-label clinical trial includes 55 children (36 boys, 19 girls; mean age 21.2 ± 28.2 months). Group A (N = 28) received lyophilized S. boulardii and group B (N = 27) received YF. The duration of diarrhea was shorter with S. boulardii but the hospital stay was reduced with YF, a...

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    OBJECTIVE: To evaluate the long-term tolerability of tolterodine extended release (ER) in children (aged 5-11 yr) with urgency urinary incontinence (UUI). METHODS: This was a multicenter, open-label extension of a 12-wk, double-blind, placebo-controlled study of tolterodine ER. Patients had UUI......-blind tolterodine ER, n=221; placebo, n=97). The majority of patients were white (90%), mean+/-SD age was 7.6+/-1.5 yr, and 54% were boys. Forty-nine percent of patients reported >/=1 AE during the study, similar to that observed in the preceding 12-wk study (42%). The most frequent AEs were urinary tract infection...

  3. 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.

  4. Safety and efficacy of adjunctive lacosamide among patients with partial-onset seizures in a long-term open-label extension trial of up to 8 years.

    Science.gov (United States)

    Rosenfeld, William; Fountain, Nathan B; Kaubrys, Gintaras; Ben-Menachem, Elinor; McShea, Cindy; Isojarvi, Jouko; Doty, Pamela

    2014-12-01

    Long-term (up to 8 years of exposure) safety and efficacy of the antiepileptic drug lacosamide was evaluated in this open-label extension trial (SP615 [ClinicalTrials.gov identifier: NCT00552305]). Patients were enrolled following participation in a double-blind trial or one of two open-label trials of adjunctive lacosamide for partial-onset seizures. Dosage adjustments of lacosamide (100-800 mg/day) and/or concomitant antiepileptic drugs were allowed to optimize tolerability and seizure reduction. Of the 370 enrolled patients, 77%, 51%, and 39% had >1, >3, or >5 years of lacosamide exposure, respectively. Median lacosamide modal dose was 400mg/day. Common treatment-emergent adverse events (TEAEs) were dizziness (39.7%), headache (20.8%), nausea (17.3%), diplopia (17.0%), fatigue (16.5%), upper respiratory tract infection (16.5%), nasopharyngitis (16.2%), and contusion (15.4%). Dizziness (2.2%) was the only TEAE that led to discontinuation in >2% of patients. Ranges for median percent reductions in seizure frequency were 47-65%, and those for ≥ 50% responder rates were 49-63% for 1-, 3-, and 5-year completer cohorts. Exposure to lacosamide for up to 8 years was generally well tolerated, with a safety profile similar to previous double-blind trials, and efficacy was maintained.

  5. 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

  6. A two-centre, open-label, randomised study of ovulation inhibition with three transdermal contraceptive patches, each containing different amounts of ethinyl estradiol and gestodene in healthy, young women.

    Science.gov (United States)

    Waellnitz, K; Duijkers, I; Klipping, C; Rautenberg, T; Rohde, B; Zurth, C

    2016-01-01

    Here we report the findings of a two-centre, open-label, randomised, Phase IIa study designed to investigate whether an ethinyl estradiol (EE)/gestodene (GSD) patch that has been developed (referred to herein as the 'EE/GSD patch') reliably inhibits ovulation in comparison with patches delivering lower doses of these hormones. The study rationale was to provide justification of the doses of EE and GSD selected for the EE/GSD patch. Healthy women, aged 18-35 years, were randomised to receive treatment with either the EE/GSD patch, a 'reduced-GSD patch' (delivering similar amounts of EE and approximately half the amount of GSD) or a 'reduced-EE/GSD patch' (delivering half the amount of EE and GSD). Treatment was administered for three 28-day cycles (three × 7 patch-wearing days, plus a 7-day patch-free interval). The primary pharmacodynamic variable was the percentage of women with ovulation in at least one of Cycles 2 and/or 3, as indicated by Hoogland score. Pharmacokinetic parameters for EE and GSD were also measured. Results indicated that the EE/GSD patch effectively suppressed ovulation, while patches delivering lower doses of EE and GSD were less effective for this purpose. All three patches showed comparable tolerability.

  7. Vitamin D3 supplementation in healthy adults: a comparison between capsule and oral spray solution as a method of delivery in a wintertime, randomised, open-label, cross-over study.

    Science.gov (United States)

    Todd, Joshua J; McSorley, Emeir M; Pourshahidi, L Kirsty; Madigan, Sharon M; Laird, Eamon; Healy, Martin; Magee, Pamela J

    2016-10-01

    Vitamin D is typically supplied in capsule form, both in trials and in clinical practice. However, little is known regarding the efficacy of vitamin D administered via oral sprays - a method that primarily bypasses the gastrointestinal absorption route. This study aimed to compare the efficacy of vitamin D3 liquid capsules and oral spray solution in increasing wintertime total 25-hydroxyvitamin D (25(OH)D) concentrations. In this randomised, open-label, cross-over trial, healthy adults (n 22) received 3000 IU (75 µg) vitamin D3 daily for 4 weeks in either capsule or oral spray form. Following a 10-week washout phase, participants received the opposite treatment for a final 4 weeks. Anthropometrics and fasted blood samples were obtained before and after supplementation, with samples analysed for total 25(OH)D, creatinine, intact parathyroid hormone and adjusted Ca concentrations. At baseline, vitamin D sufficiency (total 25(OH)D>50 nmol/l), insufficiency (31-49 nmol/l) and clinical deficiency (capsule supplementation methods (26·15 (sd 17·85) v. 30·38 (sd 17·91) nmol/l, respectively; F=1·044, adjusted r 2 0·493, P=0·313). Oral spray vitamin D3 is an equally effective alternative to capsule supplementation in healthy adults.

  8. 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

    Science.gov (United States)

    Rodriguez-Jimenez, Norma Alejandra; Garcia-Gonzalez, Carlos E.; Ayala-Lopez, Karina Patricia; Trujillo-Hernandez, Benjamin; Aguilar-Chavez, Erika Anita; Rocha-Muñoz, Alberto Daniel; Vasquez-Jimenez, Jose Clemente; Olivas-Flores, Eva; Salazar-Paramo, Mario; Corona-Sanchez, Esther Guadalupe; Vazquez-Del Mercado, Monica; Varon-Villalpando, Evangelina; Cota-Sanchez, Adolfo; Cardona-Muñoz, Ernesto German; Gamez-Nava, Jorge I.; Gonzalez-Lopez, Laura

    2014-01-01

    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. PMID:25243145

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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

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

    Directory of Open Access Journals (Sweden)

    Matalon Albert

    2011-09-01

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

  17. 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.

  18. 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.

  19. 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

  20. 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:

  1. Remifentanil-propofol analgo-sedation shortens duration of ventilation and length of ICU stay compared to a conventional regimen: A centre randomised, cross-over, open-label study in the Netherlands

    NARCIS (Netherlands)

    F.W. Rozendaal (Frans); P.E. Spronk (Peter); F.F. Snellen (Ferdinand); A. Schoen (Adri); A.R.H. van Zanten (Arthur); N.A. Foudraine (Norbert); P.G.H. Mulder (Paul); J. Bakker (Jan)

    2009-01-01

    textabstractObjective: Compare duration of mechanical ventilation (MV), weaning time, ICU-LOS (ICU-LOS), efficacy and safety of remifentanil-based regimen with conventional sedation and analgesia. Design: Centre randomised, open-label, crossover, 'real-life' study. Setting: 15 Dutch hospitals. Patie

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

    Science.gov (United States)

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

    2013-01-01

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

  3. 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...

  4. 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

  5. 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.

  6. Impact of Yoga and Meditation on Cellular Aging in Apparently Healthy Individuals: A Prospective, Open-Label Single-Arm Exploratory Study.

    Science.gov (United States)

    Tolahunase, Madhuri; Sagar, Rajesh; Dada, Rima

    2017-01-01

    This study was designed to explore the impact of Yoga and Meditation based lifestyle intervention (YMLI) on cellular aging in apparently healthy individuals. During this 12-week prospective, open-label, single arm exploratory study, 96 apparently healthy individuals were enrolled to receive YMLI. The primary endpoints were assessment of the change in levels of cardinal biomarkers of cellular aging in blood from baseline to week 12, which included DNA damage marker 8-hydroxy-2'-deoxyguanosine (8-OH2dG), oxidative stress markers reactive oxygen species (ROS), and total antioxidant capacity (TAC), and telomere attrition markers telomere length and telomerase activity. The secondary endpoints were assessment of metabotrophic blood biomarkers associated with cellular aging, which included cortisol, β-endorphin, IL-6, BDNF, and sirtuin-1. After 12 weeks of YMLI, there were significant improvements in both the cardinal biomarkers of cellular aging and the metabotrophic biomarkers influencing cellular aging compared to baseline values. The mean levels of 8-OH2dG, ROS, cortisol, and IL-6 were significantly lower and mean levels of TAC, telomerase activity, β-endorphin, BDNF, and sirtuin-1 were significantly increased (all values p < 0.05) post-YMLI. The mean level of telomere length was increased but the finding was not significant (p = 0.069). YMLI significantly reduced the rate of cellular aging in apparently healthy population.

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

    Science.gov (United States)

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

    2016-01-01

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

  8. Postural and Balance Disorders in Patients with Parkinson’s Disease: A Prospective Open-Label Feasibility Study with Two Months of Action Observation Treatment

    Directory of Open Access Journals (Sweden)

    Andrea Santamato

    2015-01-01

    Full Text Available Action observation treatment has been proposed as therapeutic option in rehabilitation of patients affected by Parkinson’s disease (PD to improve freezing of gait episodes. The purpose of this prospective open-label feasibility study was to evaluate the impact of 8-week action observation training (video-therapy for the treatment of postural instability and balance impairment in PD patients. Fifteen PD patients aged under 80 years with scores of 1 to 3 on the Hoehn and Yahr staging and without evidence of freezing of gait were recruited. They underwent 24 sessions of video-therapy training based on carefully watching video clips on motor tasks linked to balance, subsequently performing the same observed movements. No statistically significant differences were observed in the identified outcome measures with the Berg Balance Scale and the Activities-Specific Balance Confidence Scale after two months of follow-up. In the present study, a short course of action observation treatment seems to be not effective in reducing balance impairments and postural instability in patients affected by mild to moderate PD. Further studies with larger samples, longer follow-up period, and standardized protocols of action observation treatment are needed to investigate the effects of this rehabilitation technique in the management of postural and balance disorders of PD patients.

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    S.S. Stamouli

    2011-01-01

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

  11. 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.

  12. 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.

  13. Clinical efficacy comparison of Saccharomyces boulardii and yogurt fluid in acute non-bloody diarrhea in children: a randomized, controlled, open label study.

    Science.gov (United States)

    Eren, Makbule; Dinleyici, Ener C; Vandenplas, Yvan

    2010-03-01

    The purpose of this trial is to evaluate the clinical efficacy and cost/effectiveness of Saccharomyces boulardii compared with yogurt fluid (YF) in acute non-bloody diarrhea in children. This randomized, prospective open-label clinical trial includes 55 children (36 boys, 19 girls; mean age 21.2 +/- 28.2 months). Group A (N = 28) received lyophilized S. boulardii and group B (N = 27) received YF. The duration of diarrhea was shorter with S. boulardii but the hospital stay was reduced with YF, although these differences were not significant. However, diarrhea had resolved in significantly more children on day 3 in the S. boulardii group (48.5% versus 25.5%; P yogurt treatment was cheaper than S. boulardii whereas in hospitalized patients, treatment cost was similar. In conclusion, the effect of daily freshly prepared YF was comparable to S. boulardii in the treatment of acute non-bloody diarrhea in children. The duration of diarrhea was shorter in the S. boulardii group, expressed as a significantly higher number of patients with normal stools on day 3.

  14. 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.

  15. Effect of 24-h continuous rotigotine treatment on stationary and non-stationary locomotion in de novo patients with Parkinson disease in an open-label uncontrolled study.

    Science.gov (United States)

    Serrao, Mariano; Ranavolo, Alberto; Conte, Carmela; Davassi, Chiara; Mari, Silvia; Fasano, Alfonso; Chini, Giorgia; Coppola, Gianluca; Draicchio, Francesco; Pierelli, Francesco

    2015-11-01

    The aim of this study was to investigate the effect of a rotigotine transdermal patch on stationary and non-stationary locomotion in de novo Parkinson disease (PD) patients in an open-label uncontrolled study. A 3-D gait analysis system was used to investigate four different locomotor tasks: steady-state linear walking, gait initiation, gait termination and 180°-turning. A series of gait variables were measured for each locomotor task. PD patients who received rotigotine treatment (4-8 mg) displayed: (1) increased step length, gait speed, cadence and arm oscillations, and reduced double support duration and step asymmetry during steady-state linear gait; (2) increased initial step length during gait initiation; (3) increased final step length and gait speed, and decreased stability index during gait termination; (4) decreased duration of turning and head-pelvis delays during 180°-turning. The main finding that emerges from the present study is that the dopamine agonist rotigotine can improve various aspects of gait in de novo PD patients.

  16. 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.

  17. 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.

    Science.gov (United States)

    Sonnemann, Uwe; Möller, Marcus; Bilstein, Andreas

    2014-01-01

    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.

  18. 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.

  19. Investigation of a possible interaction between quetiapine and armodafinil in patients with schizophrenia: an open-label, multiple-dose study.

    Science.gov (United States)

    Darwish, Mona; Bond, Mary; Hellriegel, Edward T; Youakim, James M; Yang, Ronghua; Robertson, Philmore

    2012-09-01

    The wakefulness-promoting medication armodafinil (R-modafinil) is being studied as an adjunctive treatment for patients with schizophrenia receiving antipsychotic therapy. This open-label study in 37 adults with schizophrenia evaluated whether a drug-drug interaction occurs between armodafinil (a moderate CYP3A4 inducer) and the atypical antipsychotic quetiapine (primarily metabolized by CYP3A4). Patients were required to be on a stable dose of quetiapine ≥300 mg once daily in the evening before enrollment. Steady-state quetiapine pharmacokinetics were determined following daily administration of quetiapine alone in the evening (day 5) and then following concomitant armodafinil administration (titrated to 250 mg) daily in the morning (day 38). In 25 evaluable patients, concomitant armodafinil resulted in a statistically significant decrease in mean AUC(0-24) and C(max) values of quetiapine by 42% and 45%, respectively, versus quetiapine alone. Adverse events occurred more frequently with combination therapy and were consistent with the known profiles of the 2 drugs. No significant changes in mean PANSS negative, positive, and total scores or SANS scores were observed. Although the data do not suggest that the observed decrease in systemic exposure to quetiapine was associated with a change in disease state, patients with schizophrenia should be monitored during combination therapy with quetiapine and armodafinil.

  20. 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.

  1. 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.

  2. 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

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    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

  3. Impact of Yoga and Meditation on Cellular Aging in Apparently Healthy Individuals: A Prospective, Open-Label Single-Arm Exploratory Study

    Science.gov (United States)

    Tolahunase, Madhuri; Sagar, Rajesh

    2017-01-01

    This study was designed to explore the impact of Yoga and Meditation based lifestyle intervention (YMLI) on cellular aging in apparently healthy individuals. During this 12-week prospective, open-label, single arm exploratory study, 96 apparently healthy individuals were enrolled to receive YMLI. The primary endpoints were assessment of the change in levels of cardinal biomarkers of cellular aging in blood from baseline to week 12, which included DNA damage marker 8-hydroxy-2′-deoxyguanosine (8-OH2dG), oxidative stress markers reactive oxygen species (ROS), and total antioxidant capacity (TAC), and telomere attrition markers telomere length and telomerase activity. The secondary endpoints were assessment of metabotrophic blood biomarkers associated with cellular aging, which included cortisol, β-endorphin, IL-6, BDNF, and sirtuin-1. After 12 weeks of YMLI, there were significant improvements in both the cardinal biomarkers of cellular aging and the metabotrophic biomarkers influencing cellular aging compared to baseline values. The mean levels of 8-OH2dG, ROS, cortisol, and IL-6 were significantly lower and mean levels of TAC, telomerase activity, β-endorphin, BDNF, and sirtuin-1 were significantly increased (all values p < 0.05) post-YMLI. The mean level of telomere length was increased but the finding was not significant (p = 0.069). YMLI significantly reduced the rate of cellular aging in apparently healthy population. PMID:28191278

  4. Effects of Qianlie'an(前列安) Suppository in Patients with Chronic Prostatitis Syndrome: A Randomized Open-Labelled Prospective and Controlled Trial

    Institute of Scientific and Technical Information of China (English)

    邢俊平; 陈兴发; 杨志尚; 王明珠; 贺大林

    2003-01-01

    Objective: To evaluate the clinical efficacy of Qianlie'an(前列安,QLA) suppository via anal route administration in treating chronic prostatitis syndrome. Methods: A randomized open-labelled prospective controlled trial was carried out. The total of 120 patients with chronic prostatitis syndrome were randomly divided into 2 groups: 60 patients in the treated group who were treated with QLA suppository combined with ofloxacin, and the other 60 patients in the control group who were given ofloxacin alone. The efficacy was evaluated by WBC count in the expressed prostatic secretion (EPS) and the Chronic Prostatitis Symptom Index (CPSI) made by the National Institute of Health (NIH). The clinical effects were also observed in a 4-week follow-up. Results: All but six cases completed the trial and the follow-up.It showed that in the treated group recovery rate was 17. 2%, markedly effective rate 34. 5%, effective rate 32.8%, total markedly effective rate 51.7%, and total effective rate 84. 5%, all of which were superior to those in the control group (total markedly effective rate 32.1% and total effective rate 66.1%, respectively), P<0.01. Conclusion: Administration of QLA suppository via anal route combined with oral antibiotics is an effective therapy for chronic prostatitis syndrome. It can relieve the symptoms of chronic prostatitis syndrome markedly and rapidly. It is a new choice for treatment of the disease.

  5. Augmentation of light therapy in difficult-to-treat depressed patients: an open-label trial in both unipolar and bipolar patients

    Science.gov (United States)

    Camardese, Giovanni; Leone, Beniamino; Serrani, Riccardo; Walstra, Coco; Di Nicola, Marco; Della Marca, Giacomo; Bria, Pietro; Janiri, Luigi

    2015-01-01

    Objectives We investigated the clinical benefits of bright light therapy (BLT) as an adjunct treatment to ongoing psychopharmacotherapy, both in unipolar and bipolar difficult-to-treat depressed (DTD) outpatients. Methods In an open-label study, 31 depressed outpatients (16 unipolar and 15 bipolar) were included to undergo 3 weeks of BLT. Twenty-five completed the treatment and 5-week follow-up. Main outcome measures Clinical outcomes were evaluated by the Hamilton Depression Rating Scale (HDRS). The Snaith–Hamilton Pleasure Scale and the Depression Retardation Rating Scale were used to assess changes in anhedonia and psychomotor retardation, respectively. Results The adjunctive BLT seemed to influence the course of the depressive episode, and a statistically significant reduction in HDRS scores was reported since the first week of therapy. The treatment was well-tolerated, and no patients presented clinical signs of (hypo)manic switch during the overall treatment period. At the end of the study (after 5 weeks from BLT discontinuation), nine patients (36%, eight unipolar and one bipolar) still showed a treatment response. BLT augmentation also led to a significant improvement of psychomotor retardation. Conclusion BLT combined with the ongoing pharmacological treatment offers a simple approach, and it might be effective in rapidly ameliorating depressive core symptoms of vulnerable DTD outpatients. These preliminary results need to be confirmed in placebo-controlled, randomized, double-blind clinical trial on larger samples. PMID:26396517

  6. 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.

  7. Suppressive therapy versus episodic therapy with oral valacyclovir for recurrent herpes labialis: efficacy and tolerability in an open-label, crossover study.

    Science.gov (United States)

    Gilbert, Stanley C

    2007-04-01

    Oral valacyclovir's efficacy and tolerability as suppressive therapy versus episodic therapy were compared for recurrent herpes labialis (RHL). Subjects with a history of at least 3 RHL episodes in the past year were randomized to receive 6 months of oral valacyclovir episodic therapy at the first sign of prodrome (two 2-g doses separated by 12 hours) and 6 months of oral valacyclovir suppressive therapy (1 g once daily) for 6 months in open-label, crossover fashion. The mean +/- SE number of recurrences per 120 days of follow-up (primary endpoint) was lower with suppressive therapy (0.30 +/- 0.41) than episodic therapy (0.71 +/- 0.79) (P 180 days) for suppressive therapy (P = 0.021). Data for secondary efficacy endpoints (pain severity score, mean duration of recurrences, maximal total lesion area) showed approximately a 30% to 50% reduction in mean values with suppressive therapy compared with episodic therapy, but results were statistically significantly different between the regimens for pain severity only. The percentage of subjects with at least one adverse event over 6 months of treatment that was considered to be drug related was 3% with suppressive therapy and 6% with episodic therapy. Suppressive therapy with oral valacyclovir was more effective than episodic therapy with oral valacyclovir in reducing the frequency of recurrences of herpes labialis and prolonging the time to first recurrence and was also similarly well-tolerated.

  8. Effect of enzyme therapy and prognostic factors in 69 adults with Pompe disease: an open-label single-center study

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    de Vries Juna M

    2012-09-01

    Full Text Available Abstract Background Enzyme replacement therapy (ERT in adults with Pompe disease, a progressive neuromuscular disorder, is of promising but variable efficacy. We investigated whether it alters the course of disease, and also identified potential prognostic factors. Methods Patients in this open-label single-center study were treated biweekly with 20 mg/kg alglucosidase alfa. Muscle strength, muscle function, and pulmonary function were assessed every 3–6 months and analyzed using repeated-measures ANOVA. Results Sixty-nine patients (median age 52.1 years were followed for a median of 23 months. Muscle strength increased after start of ERT (manual muscle testing 1.4 percentage points per year (pp/y; hand-held dynamometry 4.0 pp/y; both p Relative to the pre-treatment period (49 patients with 14 months pre-ERT and 22 months ERT median follow-up, ERT affected muscle strength positively (manual muscle testing +3.3 pp/y, p Conclusions We conclude that ERT positively alters the natural course of Pompe disease in adult patients; muscle strength increased and upright FVC stabilized. Functional outcome is probably best when ERT intervention is timely.

  9. Postural and Balance Disorders in Patients with Parkinson's Disease: A Prospective Open-Label Feasibility Study with Two Months of Action Observation Treatment.

    Science.gov (United States)

    Santamato, Andrea; Ranieri, Maurizio; Cinone, Nicoletta; Stuppiello, Lucia Anna; Valeno, Giovanni; De Sanctis, Jula Laura; Fortunato, Francesca; Solfrizzi, Vincenzo; Greco, Antonio; Seripa, Davide; Panza, Francesco

    2015-01-01

    Action observation treatment has been proposed as therapeutic option in rehabilitation of patients affected by Parkinson's disease (PD) to improve freezing of gait episodes. The purpose of this prospective open-label feasibility study was to evaluate the impact of 8-week action observation training (video-therapy) for the treatment of postural instability and balance impairment in PD patients. Fifteen PD patients aged under 80 years with scores of 1 to 3 on the Hoehn and Yahr staging and without evidence of freezing of gait were recruited. They underwent 24 sessions of video-therapy training based on carefully watching video clips on motor tasks linked to balance, subsequently performing the same observed movements. No statistically significant differences were observed in the identified outcome measures with the Berg Balance Scale and the Activities-Specific Balance Confidence Scale after two months of follow-up. In the present study, a short course of action observation treatment seems to be not effective in reducing balance impairments and postural instability in patients affected by mild to moderate PD. Further studies with larger samples, longer follow-up period, and standardized protocols of action observation treatment are needed to investigate the effects of this rehabilitation technique in the management of postural and balance disorders of PD patients.

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

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    Dunbar Lala M

    2005-05-01

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

  11. 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.

    Science.gov (United States)

    Patel, Manish V; Patel, Kalapi B; Gupta, Shivenarain; Michalsen, Andreas; Stapelfeldt, Elmar; Kessler, Christian S

    2015-01-01

    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.

  12. International, open-label, noncomparative, clinical trial of micafungin alone and in combination for treatment of newly diagnosed and refractory candidemia.

    Science.gov (United States)

    Ostrosky-Zeichner, L; Kontoyiannis, D; Raffalli, J; Mullane, K M; Vazquez, J; Anaissie, E J; Lipton, J; Jacobs, P; van Rensburg, J H Jansen; Rex, J H; Lau, W; Facklam, D; Buell, D N

    2005-10-01

    Candida spp. are the fourth leading cause of bloodstream infections, and non-albicans species are increasing in importance. Micafungin is a new echinocandin antifungal agent with excellent in vitro activity against Candida spp. Pediatric, neonatal, and adult patients with new or refractory candidemia were enrolled into this open-label, noncomparative, international study. The initial dose of micafungin was 50 mg/d (1 mg/kg for patients <40 kg) for infections due to C. albicans and 100 mg/d (2 mg/kg for patients <40 kg) for infections due to other species. Dose escalation was allowed. Maximum length of therapy was 42 days. A total of 126 patients were evaluable (received at least five doses of micafungin). Success (complete or partial response) was seen in 83.3% patients overall. Success rates for treatment of infections caused by the most common Candida spp. were as follows: C. albicans 85.1%, C. glabrata 93.8%, C. parapsilosis 86.4%, and C. tropicalis 83.3%. Serious adverse events related to micafungin were uncommon. Micafungin shows promise as a safe and effective agent for the treatment of newly diagnosed and refractory cases of candidemia. Large-scale, randomized, controlled trials are warranted.

  13. 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 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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

    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...... similar between selumetinib and temozolomide groups (11.1% and 10.7%, respectively). However, five of the six selumetinib partial responders were BRAF mutated. Frequently reported adverse events with selumetinib were dermatitis acneiform (papular pustular rash; 59.6%), diarrhea (56.6%), nausea (50.......5%) and peripheral edema (40.4%), whereas nausea (64.2%), constipation (47.4%) and vomiting (44.2%) were reported with temozolomide. CONCLUSIONS: No significant difference in progression-free survival was observed between patients with unresectable stage III/IV melanoma unselected for BRAF/NRAS mutations, who...

  19. 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

  20. 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

  1. Mobilisation of hematopoietic CD34+ precursor cells in patients with acute stroke is safe--results of an open-labeled non randomized phase I/II trial.

    Directory of Open Access Journals (Sweden)

    Sandra Boy

    Full Text Available BACKGROUND: Regenerative strategies in the treatment of acute stroke may have great potential. Hematopoietic growth factors mobilize hematopoietic stem cells and may convey neuroprotective effects. We examined the safety, potential functional and structural changes, and CD34(+ cell-mobilization characteristics of G-CSF treatment in patients with acute ischemic stroke. METHODS AND RESULTS: Three cohorts of patients (8, 6, and 6 patients per cohort were treated subcutaneously with 2.5, 5, or 10 µg/kg body weight rhG-CSF for 5 consecutive days within 12 hrs of onset of acute stroke. Standard treatment included i.v. thrombolysis. Safety monitoring consisted of obtaining standardized clinical assessment scores, monitoring of CD34(+ stem cells, blood chemistry, serial neuroradiology, and neuropsychology. Voxel-guided morphometry (VGM enabled an assessment of changes in the patients' structural parenchyma. 20 patients (mean age 55 yrs were enrolled in this study, 5 of whom received routine thrombolytic therapy with r-tPA. G-CSF treatment was discontinued in 4 patients because of unrelated adverse events. Mobilization of CD34(+ cells was observed with no concomitant changes in blood chemistry, except for an increase in the leukocyte count up to 75,500/µl. Neuroradiological and neuropsychological follow-up studies did not disclose any specific G-CSF toxicity. VGM findings indicated substantial atrophy of related hemispheres, a substantial increase in the CSF space, and a localized increase in parenchyma within the ischemic area in 2 patients. CONCLUSIONS: We demonstrate a good safety profile for daily administration of G-CSF when begun within 12 hours after onset of ischemic stroke and, in part in combination with routine i.v. thrombolysis. Additional analyses using VGM and a battery of neuropsychological tests indicated a positive functional and potentially structural effect of G-CSF treatment in some of our patients. TRIAL REGISTRATION: German Clinical Trial Register DRKS 00000723.

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

    Science.gov (United States)

    2016-11-23

    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

  3. 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

  4. 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.

  5. 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.

  6. 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.

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

    Science.gov (United States)

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

    2012-03-01

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

  8. 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.

  9. Multicentre, randomized, open-label study of on-demand treatment with two prophylaxis regimens of recombinant coagulation factor IX in haemophilia B subjects.

    Science.gov (United States)

    Valentino, L A; Rusen, L; Elezovic, I; Smith, L M; Korth-Bradley, J M; Rendo, P

    2014-05-01

    Few randomized studies have reported on the use of factor IX (FIX) for secondary prophylaxis in haemophilia B patients. This study aimed to evaluate the efficacy and safety of two secondary prophylaxis regimens of recombinant coagulation FIX, nonacog alfa, compared with on-demand therapy. Male subjects aged 6-65 years with severe or moderately severe haemophilia B (FIX:C ≤ 2, n = 50) and ≥12 bleeding episodes (including ≥6 haemarthroses episodes) within 12 months of study participation were enrolled in this multicentre, randomized, open-label, four-period crossover trial. The primary measure was the annualized bleeding rate (ABR) of two prophylactic regimens vs. on-demand therapy. In the intent-to-treat group, mean ABR values were 35.1, 2.6 and 4.6 for the first on-demand period, the 50 IU kg(-1) twice-weekly period, and the 100 IU kg(-1) once-weekly period respectively. Differences in ABR between the first on-demand period and both prophylaxis regimens were significant (P < 0.0001); no significant differences were observed between prophylaxis regimens (P = 0.22). Seven serious adverse events occurred in five subjects, none related to study drug. Results demonstrated that secondary prophylaxis therapy with nonacog alfa 50 IU kg(-1) twice weekly or 100 IU kg(-1) once weekly reduced ABR by 89.4% relative to on-demand treatment. Both prophylaxis regimens demonstrated favourable safety profiles in subjects with haemophilia B.

  10. INFLUENCE OF GRADED AEROBIC EXERCISE ON QUALITY OF LIFE IN POST SURGICAL MITRAL VALVE DISEASE INDIVIDUAL A PROSPECTIVE RANDOMIZED OPEN LABEL STUDY

    Directory of Open Access Journals (Sweden)

    Shanthi C

    2016-10-01

    Full Text Available Background: Post surgical mitral valve disease individual focus their cardiac rehabilitation training on two major goal that is to improve cardiac output response exercises and place an important role in determining exercise tolerance and to improve quality of life. Cardiac rehabilitation programs involve prescribed exercise and education however various other method are being used to improve quality of life. But our study to find out the effectiveness of graded aerobic exercise protocol on ejection fraction and quality of life in post surgical mitral valve disease individuals. Methods: The study design was open label studies total of 100 post surgical mitral valve disease individuals patients from the age group of 20-60 years were recruited from SVIMS hospital. They were randomly divided into two groups. Group I underwent a twelve week structured graded individually tailored exercises. The group II received only none graded (not individualized exercise training. The ejection fraction and quality of life was measured before and after 12 weeks of exercise training for two groups. Results: Repeated measures ANOVA was used to compare mean values of continuous variables between baseline and at the time of discharge and three months after surgery for each parameter. Comparison of means between groups was done by the unpaired student t test. Mean age of the subjects was 40.18±10.29. There was a significant increase in the ejection fraction in the group I(61.34±2.49 to 64.4±3.31 compared to with the group II (61.06±2.51. to 61.62 ±2.37. QOL had improved in group I than group II at p<0.05. Conclusion: A 12 week structured graded aerobic exercise training significantly improved ejection fraction and quality of life in post surgical mitral valve disease individuals.

  11. An open-label, two-period comparative study on pharmacokinetics and safety of a combined ethinylestradiol/gestodene transdermal contraceptive patch

    Science.gov (United States)

    Zhang, Chao; Li, Haiyan; Xiong, Xin; Zhai, Suodi; Wei, Yudong; Zhang, Shuang; Zhang, Yuanyuan; Xu, Lin; Liu, Li

    2017-01-01

    We investigated the pharmacokinetics and safety profiles of a newly developed combined ethinylestradiol (EE)/gestodene (GSD) transdermal contraceptive patch after a single-dose administration and compared with the market available tablet formulation in healthy adult subjects. An open-label, two-period comparative study was conducted in 12 healthy women volunteers. A single dose of the study combined EE/GE transdermal contraceptive patch and oral tablet (Milunet®) were administered. Blood samples at different time points after dose were collected, and concentrations were analyzed. A reliable, highly sensitive and accurate high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS) assay method was developed in this study to determine the plasma concentrations of EE and GSD. Compared to the tablet, the study patch had a significantly decreased maximum plasma concentration (Cmax), extended time to reach the Cmax and half-life, as well as increased clearance and apparent volume of distribution. The half-lives of EE and GSD of the patch were 3.3 and 2.2 times, respectively, than the half-life of the tablet. The areas under the plasma concentration–time curve (AUCs) of EE and GSD of the patch were 8.0 and 16.2 times, respectively, than the AUC of the tablet. No severe adverse event was observed during the whole study, and the general safety was acceptable. In conclusion, compared to the oral tablet Milunet, the study contraceptive patch was well tolerated and showed potent drug exposure, significant extended half-life and stable drug concentrations.

  12. 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

  13. 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

  14. 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.

  15. An open-label, two-period comparative study on pharmacokinetics and safety of a combined ethinylestradiol/gestodene transdermal contraceptive patch.

    Science.gov (United States)

    Zhang, Chao; Li, Haiyan; Xiong, Xin; Zhai, Suodi; Wei, Yudong; Zhang, Shuang; Zhang, Yuanyuan; Xu, Lin; Liu, Li

    2017-01-01

    We investigated the pharmacokinetics and safety profiles of a newly developed combined ethinylestradiol (EE)/gestodene (GSD) transdermal contraceptive patch after a single-dose administration and compared with the market available tablet formulation in healthy adult subjects. An open-label, two-period comparative study was conducted in 12 healthy women volunteers. A single dose of the study combined EE/GE transdermal contraceptive patch and oral tablet (Milunet(®)) were administered. Blood samples at different time points after dose were collected, and concentrations were analyzed. A reliable, highly sensitive and accurate high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS) assay method was developed in this study to determine the plasma concentrations of EE and GSD. Compared to the tablet, the study patch had a significantly decreased maximum plasma concentration (Cmax), extended time to reach the Cmax and half-life, as well as increased clearance and apparent volume of distribution. The half-lives of EE and GSD of the patch were 3.3 and 2.2 times, respectively, than the half-life of the tablet. The areas under the plasma concentration-time curve (AUCs) of EE and GSD of the patch were 8.0 and 16.2 times, respectively, than the AUC of the tablet. No severe adverse event was observed during the whole study, and the general safety was acceptable. In conclusion, compared to the oral tablet Milunet, the study contraceptive patch was well tolerated and showed potent drug exposure, significant extended half-life and stable drug concentrations.

  16. An open-label, two-period comparative study on pharmacokinetics and safety of a combined ethinylestradiol/gestodene transdermal contraceptive patch

    Directory of Open Access Journals (Sweden)

    Zhang C

    2017-03-01

    Full Text Available Chao Zhang,1 Haiyan Li,2 Xin Xiong,1 Suodi Zhai,1 Yudong Wei,2 Shuang Zhang,2 Yuanyuan Zhang,1 Lin Xu,2 Li Liu1 1Department of Pharmacy, 2Institute of Clinical Trial, Peking University Third Hospital, Beijing, People’s Republic of China Abstract: We investigated the pharmacokinetics and safety profiles of a newly developed combined ethinylestradiol (EE/gestodene (GSD transdermal contraceptive patch after a single-dose administration and compared with the market available tablet formulation in healthy adult subjects. An open-label, two-period comparative study was conducted in 12 healthy women volunteers. A single dose of the study combined EE/GE transdermal contraceptive patch and oral tablet (Milunet® were administered. Blood samples at different time points after dose were collected, and concentrations were analyzed. A reliable, highly sensitive and accurate high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS assay method was developed in this study to determine the plasma concentrations of EE and GSD. Compared to the tablet, the study patch had a significantly decreased maximum plasma concentration (Cmax, extended time to reach the Cmax and half-life, as well as increased clearance and apparent volume of distribution. The half-lives of EE and GSD of the patch were 3.3 and 2.2 times, respectively, than the half-life of the tablet. The areas under the plasma concentration–time curve (AUCs of EE and GSD of the patch were 8.0 and 16.2 times, respectively, than the AUC of the tablet. No severe adverse event was observed during the whole study, and the general safety was acceptable. In conclusion, compared to the oral tablet Milunet, the study contraceptive patch was well tolerated and showed potent drug exposure, significant extended half-life and stable drug concentrations. Keywords: pharmacokinetics, safety, ethinylestradiol/gestodene, transdermal contraceptive patch

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

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    Kühne U

    2016-10-01

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

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

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

    2005-08-01

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

  19. HEAD - TO - HEAD COMPARISON OF TOLERABILITY AND ACCEPTABILITY OF SINGLE DOSE OF FOUR TOPICAL NSAIDS IN PATIENTS UNDERGOING CATARACT SURGERY : A RANDOMIZED OPEN LABEL PARALLEL GROUP STUDY

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    Chandra Sekhar

    2015-07-01

    Full Text Available INTRODUCTION : Ophthalmic NSAIDs are used to control pain , discomfort and inflammation associated with ocular conditions and also , following ophthalmic cataract surgeries. These drugs can cause ocular discomfort following administration which lasts for a short duration. However , there exist differences in the intensity and duration of burning sensation among the c ommonly used ophthalmic NSAIDs. Hence , we evaluated the tolerability and acceptability of four topical NSAIDS i.e. , 0.3% nepafenac (N , 0.5% ketorolac (K , 0.4% ketorolac (K LS and 0.09% bromfenac (B after instilling a single drop. METHODS: This randomized , open label , parallel group study was conducted in the department of Ophthalmology in Narayana Medical College , Nellore. A total number of 80 patients participated in the study. Randomization list was computer generated in a ratio of 1:1:1:1 of N , K , K L Sand B. Each patient received one drop of the study drug either in right or left eye which was also decidedat random.Patients of either gender above21 years of age , having no ocular surface pathology and eligible for cataract surgery were include d in the study. Outcome variables included ocular burning intensity on VAS (0 - 100 mm at 0 min (immediately , 2 min and 6 min after administration of medications , time to complete pain relief and global medication performance rated by patient as 0 (bad , 1 (fair , 2(good or 3 (severe . RESULTS: The mean age of patients was 52.85±17.46 years. All groups were age matched , however there were more females than males (pN>K LS >K on global medication performance. CONCLUSION: Bromfenac had better tolerability and acceptability as compared to other tested topical NSAIDs , which was in the order of B>N> K LS >K.

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

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    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.

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

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    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

  2. 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

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    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

  3. Bioavailability of orally administered rhGM-CSF: a single-dose, randomized, open-label, two-period crossover trial.

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    Wenping Zhang

    Full Text Available BACKGROUND: Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF is usually administered by injection, and its oral administration in a clinical setting has been not yet reported. Here we demonstrate the bioavailability of orally administered rhGM-CSF in healthy volunteers. The rhGM-CSF was expressed in Bombyx mori expression system (BmrhGM-CSF. METHODS AND FINDINGS: Using a single-dose, randomized, open-label, two-period crossover clinical trial design, 19 healthy volunteers were orally administered with BmrhGM-CSF (8 microg/kg and subcutaneously injected with rhGM-CSF (3.75 microg/kg respectively. Serum samples were drawn at 0.0h, 0.5h ,0.75h,1.0h,1.5h,2.0h ,3.0h,4.0h,5.0h,6.0h,8.0h,10.0h and 12.0h after administrations. The hGM-CSF serum concentrations were determined by ELISA. The AUC was calculated using the trapezoid method. The relative bioavailability of BmrhGM-CSF was determined according to the AUC ratio of both orally administered and subcutaneously injected rhGM-CSF. Three volunteers were randomly selected from 15 orally administrated subjects with ELISA detectable values. Their serum samples at the 0.0h, 1.0h, 2.0h, 3.0h and 4.0h after the administrations were analyzed by Q-Trap MS/MS TOF. The different peaks were revealed by the spectrogram profile comparison of the 1.0h, 2.0h, 3.0h and 4.0h samples with that of the 0.0h sample, and further analyzed using both Enhanced Product Ion (EPI scanning and Peptide Mass Fingerprinting Analysis. The rhGM-CSF was detected in the serum samples from 15 of 19 volunteers administrated with BmrhGM-CSF. Its bioavailability was observed at an average of 1.0%, with the highest of 3.1%. The rhGM-CSF peptide sequences in the serum samples were detected by MS analysis, and their sizes ranging from 2,039 to 7,336 Da. CONCLUSIONS: The results demonstrated that the oral administered BmrhGM-CSF was absorbed into the blood. This study provides an approach for an oral administration of

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

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    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

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

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    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

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

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    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

  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.

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    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. Relative Bioavailabilities of Lisdexamfetamine Dimesylate and d-Amphetamine in Healthy Adults in an Open-Label, Randomized, Crossover Study After Mixing Lisdexamfetamine Dimesylate With Food or Drink

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    Ermer, James; Corcoran, Mary; Lasseter, Kenneth

    2016-01-01

    Background: This open-label, crossover study examined lisdexamfetamine dimesylate (LDX) and d-amphetamine pharmacokinetics in healthy adults after administration of an intact LDX capsule or after the capsule was emptied into orange juice or yogurt and the contents consumed. Methods: Healthy adult volunteers (N = 30) were administered a 70-mg LDX capsule or the contents of a 70-mg capsule mixed with yogurt or orange juice using a 3-way crossover design. Blood samples were collected serially for up to 96 hours after dose. Pharmacokinetic endpoints included maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve from zero to infinity (AUC0–∞) or to last assessment (AUClast). Relative LDX and d-amphetamine bioavailabilities from the contents of a 70-mg LDX capsule mixed with orange juice or yogurt were compared with those from the intact LDX capsule using bioequivalence-testing procedures. Results: Geometric least squares mean ratios (90% confidence intervals [CIs]) for d-amphetamine (active moiety) were within the prespecified bioequivalence range (0.80–1.25) when the contents of a 70-mg LDX capsule were mixed with orange juice [Cmax: 0.971 (0.945, 0.998); AUC0–∞: 0.986 (0.955, 1.019); AUClast: 0.970 (0.937, 1.004)] or yogurt [Cmax: 0.970 (0.944, 0.997); AUC0–∞: 0.945 (0.915, 0.976); AUClast: 0.944 (0.912, 0.977)]. Geometric least squares mean ratios (90% CIs) for LDX (inactive prodrug) were below the accepted range when the contents of a 70-mg LDX capsule were mixed with orange juice [Cmax: 0.641 (0.582, 0.707); AUC0–∞: 0.716 (0.647, 0.792); AUClast: 0.708 (0.655, 0.766)]; the lower 90% CI for Cmax [0.828 (0.752, 0.912)] was below the accepted range when the contents of a 70-mg LDX capsule were mixed with yogurt. Conclusions: Relative bioavailability of d-amphetamine (the active moiety) did not differ across administrations, which suggests that emptying an LDX capsule into orange juice or yogurt and consuming it

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

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    Dorsch Oliver

    2012-06-01

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

  10. Nitrous oxide-oxygen mixture during care of bedsores and painful ulcers in the elderly: a randomized, crossover, open-label pilot study.

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    Paris, Adeline; Horvath, Rémi; Basset, Pierre; Thiery, Stéphane; Couturier, Pascal; Franco, Alain; Bosson, Jean-Luc

    2008-02-01

    Bedsore and ulcer care can often be painful and no standardized analgesic method exists today for pain relief during treatment in adults and the elderly. To evaluate the analgesic efficacy of a nitrous oxide-oxygen mixture vs. morphine during painful bedsore and ulcer care in adult and elderly patients, we conducted a randomized, crossover, multicenter, prospective, open-label, pilot study. Thirty-four inpatients, aged 53-96 years (median 84 years), were recruited in Grenoble University Hospital, Annecy Hospital and Chambéry Hospital, France, from January to June 2001. Each of the 34 patients received morphine (M), nitrous oxide-oxygen mixture (E), or morphine+nitrous oxide-oxygen mixture (ME) during painful care in a crossover protocol. Treatments were changed every two days and the study duration was six days. Analgesia was evaluated before and after each care session using a behavioral scale to evaluate pain in noncommunicating adults (ECPA), a visual analog scale (VAS), a global hetero-evaluation scale (GHES), and the DOLOPLUS-2 scale. There was a significant overall difference (P<0.01) among the three treatments. On the ECPA, the average difference after and before care was +5.2+/-8.6 (M), -0.3+/-8 (E), and -0.6+/-7.4 (ME), respectively. There was a significant difference between M and E, and M and ME (each P<0.01). No difference was found between E and ME (P=0.97). There were similar significant differences in the GHES and DOLOPLUS-2 scales (all tests P<0.01). Post hoc comparisons showed a significant difference (P<0.01) between M and E, and between M and ME without any additional effect for M+E. No differences were found with regard to safety or tolerability. This pilot study demonstrates the superiority of nitrous oxide-oxygen mixture over morphine for analgesia. This experience suggests that this mixture has ease of use, rapid effect, and limited contraindications when used during painful bedsore and ulcer care in elderly patients. Furthermore, it is well

  11. 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

  12. 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.

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

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    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. An open-label, flexible-dose study of paliperidone extended-release in Chinese patients with first-onset psychosis

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    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

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

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    Saeed T

    2014-07-01

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

  16. 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

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

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    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

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

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    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

  19. 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)、

  20. 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

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    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.

  1. Lobeglitazone and pioglitazone as add-ons to metformin for patients with type 2 diabetes: a 24-week, multicentre, randomized, double-blind, parallel-group, active-controlled, phase III clinical trial with a 28-week extension.

    Science.gov (United States)

    Jin, S-M; Park, C-Y; Cho, Y M; Ku, B J; Ahn, C W; Cha, B-S; Min, K W; Sung, Y A; Baik, S H; Lee, K W; Yoon, K-H; Lee, M-K; Park, S W

    2015-06-01

    We aimed to compare the efficacy and safety of lobeglitazone and pioglitazone as add-ons to metformin in patients with type 2 diabetes. Patients who were inadequately controlled by metformin were randomized and treated once daily with either lobeglitazone (0.5 mg, n = 128) or pioglitazone (15 mg, n = 125) for 24 weeks, with a 28-week extension trial of lobeglitazone treatment in patients who consented. The primary endpoint was the change in glycated haemoglobin (HbA1c) concentration from baseline to week 24. At week 24, the mean change from baseline in HbA1c was -0.74% for the lobeglitazone group and -0.74% for the pioglitazone group, with a mean difference of 0.01% [95% confidence interval (CI) of difference, -0.16 to 0.18]. The effects of lobeglitazone on lipid variables and the adverse events associated with lobeglitazone were similar to those observed with pioglitazone. Lobeglitazone was not inferior to pioglitazone as an add-on to metformin in terms of their efficacy and safety.

  2. 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

  3. 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.

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    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

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

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    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

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

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    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

  6. Efficacy and safety of Tofacitinib in patients with active rheumatoid arthritis resistant to conventional therapy: Preliminary results of an open-label clinical trial

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    E. L. Luchikhina

    2016-01-01

    Full Text Available Despite the advances in the therapy of rheumatoid arthritis (RA, which are associated with the use of biological anti-rheumatic drugs, the problemof effective treatment of RA is not still solved. Inclusion of new methods in treatment strategies, in particular the so-called «small molecules», i.e. synthetic compounds acting on intracellular signaling pathways, such as Tofacitinib (TOFA approved for use in rheumatologic practice, is very important.Objective: to evaluate the efficacy and safety of therapy with TOFA in combination with synthetic disease-modifying anti-rheumatic drugs (s-DMARDs, primarily methotrexate (MTX in in patients with active RA in real clinical practice.Subjects and methods. This ongoing open-label trial is a part of the scientific program «Russian Investigation of Methotrexate and Biologics in Early Active Inflammatory Arthritis» (REMARCA that explores the possibility of adapting the «treat-to-target» strategy in real prac-tice in Russia. The study included RA patients with moderate to high disease activity despite treatment with MTX or other DMARDs. A total of 41 patients with RA were included (8 males, 33 females; mean age 52.6±14.2 years, disease duration 47.2±49.7 months, 82.9% RF+ and 80.5% anti-CCP+,DAS28-ESR 5.45±0.95, SDAI 30.2±12.2. All the patients had previously received s-DMARDs; 12 (29.3% patients also had biological DMARDs (1 to 4 biologics. Oral TOFA 5 mg in combination with MTX or leflunomide was administered twice daily to 40 and 1 patients, respectively, with the possibility of increasing the dose up to 10 mg BID. To date, 37 and 12 patients received TOFA for 3 and 6 months, respectively.Results. TOFA was used as a second-line drug (after s-DMARDs failure in 29 (70.7%, as a third line drug (after s-DMARDs and biologics failure in 12 (29.3% patients. The dose was escalated to 10 mg BID in 13 (31.2% patients, on the average, 11.2±1.7 weeks after treatment initiation. TOFA was not

  7. 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

  8. 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

  9. A Phase I study evaluating the safety and immunogenicity of MVA85A, a candidate TB vaccine, in HIV-infected adults.

    Science.gov (United States)

    Minassian, Angela M; Rowland, Rosalind; Beveridge, Natalie E R; Poulton, Ian D; Satti, Iman; Harris, Stephanie; Poyntz, Hazel; Hamill, Matthew; Griffiths, Kristin; Sander, Clare R; Ambrozak, David R; Price, David A; Hill, Brenna J; Casazza, Joseph P; Douek, Daniel C; Koup, Richard A; Roederer, Mario; Winston, Alan; Ross, Jonathan; Sherrard, Jackie; Rooney, Guy; Williams, Nicola; Lawrie, Alison M; Fletcher, Helen A; Pathan, Ansar A; McShane, Helen

    2011-01-01

    Objectives Control of the tuberculosis (TB) epidemic is a global health priority and one that is likely to be achieved only through vaccination. The critical overlap with the HIV epidemic requires any effective TB vaccine regimen to be safe in individuals who are infected with HIV. The objectives of this clinical trial were to evaluate the safety and immunogenicity of a leading candidate TB vaccine, MVA85A, in healthy, HIV-infected adults. Design This was an open-label Phase I trial, performed in 20 healthy HIV-infected, antiretroviral-naïve subjects. Two different doses of MVA85A were each evaluated as a single immunisation in 10 subjects, with 24 weeks of follow-up. The safety of MVA85A was assessed by clinical and laboratory markers, including regular CD4 counts and HIV RNA load measurements. Vaccine immunogenicity was assessed by ex vivo interferon γ (IFN-γ) ELISpot assays and flow-cytometric analysis. Results MVA85A was safe in subjects with HIV infection, with an adverse-event profile comparable with historical data from previous trials in HIV-uninfected subjects. There were no clinically significant vaccine-related changes in CD4 count or HIV RNA load in any subjects, and no evidence from qPCR analyses to indicate that MVA85A vaccination leads to widespread preferential infection of vaccine-induced CD4 T cell populations. Both doses of MVA85A induced an antigen-specific IFN-γ response that was durable for 24 weeks, although of a lesser magnitude compared with historical data from HIV-uninfected subjects. The functional quality of the vaccine-induced T cell response in HIV-infected subjects was remarkably comparable with that observed in healthy HIV-uninfected controls, but less durable. Conclusion MVA85A is safe and immunogenic in healthy adults infected with HIV. Further safety and efficacy evaluation of this candidate vaccine in TB- and HIV-endemic areas is merited.

  10. New film-coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower-risk MDS: Results of the randomized, phase II ECLIPSE study.

    Science.gov (United States)

    Taher, Ali T; Origa, Raffaella; Perrotta, Silverio; Kourakli, Alexandra; Ruffo, Giovan Battista; Kattamis, Antonis; Goh, Ai-Sim; Cortoos, Annelore; Huang, Vicky; Weill, Marine; Merino Herranz, Raquel; Porter, John B

    2017-01-31

    Once-daily deferasirox dispersible tablets (DT) have a well-defined safety and efficacy profile and, compared with parenteral deferoxamine, provide greater patient adherence, satisfaction, and quality of life. However, barriers still exist to optimal adherence, including gastrointestinal tolerability and palatability, leading to development of a new film-coated tablet (FCT) formulation that can be swallowed with a light meal, without the need to disperse into a suspension prior to consumption. The randomized, open-label, phase II ECLIPSE study evaluated the safety of deferasirox DT and FCT formulations over 24 weeks in chelation-naïve or pre-treated patients aged ≥10 years, with transfusion-dependent thalassemia or IPSS-R very-low-, low-, or intermediate-risk myelodysplastic syndromes. One hundred seventy-three patients were randomized 1:1 to DT (n = 86) or FCT (n = 87). Adverse events (overall), consistent with the known deferasirox safety profile, were reported in similar proportions of patients for each formulation (DT 89.5%; FCT 89.7%), with a lower frequency of severe events observed in patients receiving FCT (19.5% vs. 25.6% DT). Laboratory parameters (serum creatinine, creatinine clearance, alanine aminotransferase, aspartate aminotransferase and urine protein/creatinine ratio) generally remained stable throughout the study. Patient-reported outcomes showed greater adherence and satisfaction, better palatability and fewer concerns with FCT than DT. Treatment compliance by pill count was higher with FCT (92.9%) than with DT (85.3%). This analysis suggests deferasirox FCT offers an improved formulation with enhanced patient satisfaction, which may improve adherence, thereby reducing frequency and severity of iron overload-related complications.

  11. Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treatment of Uncomplicated Plasmodium falciparum Malaria in Children Aged Less than 15 Years in Guinea-Bissau - An Open-Label Non-Inferiority Randomised Clinical Trial

    DEFF Research Database (Denmark)

    Ursing, Johan; Rombo, Lars; Rodrigues, Amabelia;

    2016-01-01

    BACKGROUND: Artemether-lumefantrine (AL) was introduced for treatment of uncomplicated malaria in Guinea-Bissau in 2008. Malaria then resurged and recurrent malaria after treatment with AL and stock-outs of AL were common. This study therefore aimed to assess the efficacy of AL and identify...... an alternative second line antimalarial. Dihydroartemisinin-piperaquine (DP) was chosen as it has been shown to be safe and efficacious and to reduce the incidence of recurrent malaria. METHODS AND FINDINGS: In a multicentre randomised open-label non-inferiority clinical trial, AL or DP were given over 3 days.......022. In a modified intention to treat analysis in which treatment failures day 0 and reinfections were also considered as treatment failures adequate clinical and parasitological responses were 94% and 97% (OR 0.42 [95% CI, 0.13-1.38], p = 0.15). Parasite clearance and symptom resolution were similar with both...

  12. 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.

  13. 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.

  14. Long-Term Teduglutide for the Treatment of Patients With Intestinal Failure Associated With Short Bowel Syndrome

    DEFF Research Database (Denmark)

    Schwartz, Lauren K; O'Keefe, Stephen J D; Fujioka, Ken;

    2016-01-01

    OBJECTIVES: In the pivotal 24-week, phase III, placebo-controlled trial, teduglutide significantly reduced parenteral support (PS) requirements in patients with short bowel syndrome (SBS). STEPS-2 was a 2-year, open-label extension of that study designed to evaluate long-term safety and efficacy...

  15. Effectiveness of a Therapeutic Summer Camp for Children with ADHD: Phase I Clinical Intervention Trial

    Science.gov (United States)

    Hantson, Julie; Wang, Pan Pan; Grizenko-Vida, Michael; Ter-Stepanian, Marina; Harvey, William; Joober, Ridha; Grizenko, Natalie

    2012-01-01

    Objective: The objective of this study was to evaluate the effectiveness of a 2-week therapeutic summer day camp for children with ADHD, which included a social skills training program and parent psychoeducation and training program. This was an open-label, nonrandomized Phase I Clinical Intervention Trial. Method: Parents completed the Weiss…

  16. Protocol of a randomised controlled, open-label trial of ex vivo normothermic perfusion versus static cold storage in donation after circulatory death renal transplantation

    Science.gov (United States)

    Hosgood, Sarah A; Saeb-Parsy, Kourosh; Wilson, Colin; Callaghan, Christopher; Collett, Dave; Nicholson, Michael L

    2017-01-01

    Introduction Ex vivo normothermic perfusion (EVNP) is a novel technique that reconditions the kidney and restores renal function prior to transplantation. Phase I data from a series of EVNP in extended criteria donor kidneys have established the safety and feasibility of the technique in clinical practice. Methods and analysis This is a UK-based phase II multicentre randomised controlled trial to assess the efficacy of EVNP compared with the conventional static cold storage technique in donation after circulatory death (DCD) kidney transplantation. 400 patients receiving a kidney from a DCD donor (categories III and IV, controlled) will be recruited into the study. On arrival at the transplant centre, kidneys will be randomised to receive either EVNP (n=200) or remain in static cold storage (n=200). Kidneys undergoing EVNP will be perfused with an oxygenated packed red cell solution at near body temperature for 60 min prior to transplantation. The primary outcome measure will be determined by rates of delayed graft function (DGF) defined as the need for dialysis in the first week post-transplant. Secondary outcome measures include incidences of primary non-function, the duration of DGF, functional DGF defined as <10% fall in serum creatinine for 3 consecutive days in the first week post-transplant, creatinine reduction ratio days 2 and 5, length of hospital stay, rates of biopsy-proven acute rejection, serum creatinine and estimated glomerular filtration rate at 1, 3, 6 and 12 months post-transplant and patient and allograft survival. The EVNP assessment score will be recorded and the level of fibrosis and inflammation will also be measured using tissue, blood and urine samples. Ethics and dissemination. The study has been approved by the National Health Service (NHS) Health Research Authority Research Ethics Committee. The results are expected to be published in 2020. Trial registration number ISRCTN15821205; Pre-results. PMID:28115329

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  18. Do open label blinded outcome studies of novel anticoagulants versus warfarin have equivalent validity to those carried out under double-blind conditions?

    Science.gov (United States)

    O'Neil, William M; Welner, Sharon A; Lip, Gregory Y H

    2013-03-01

    Recent anticoagulants for stroke prevention in AF have been tested in active comparator controlled studies versus warfarin using two designs: double-blind, double-dummy and prospective randomised, open blinded endpoint (PROBE). The former requires elaborate procedures to maintain blinding, while PROBE does not. Outcomes of double-blind and PROBE designed studies of novel anticoagulants for AF, focusing on warfarin controls, were explored. Major, Phase III warfarin-controlled trials for stroke prevention in AF were identified. Odds ratios (ORs) of key outcomes for active comparators versus VKA and event rates for VKA arms were compared between designs, in context of baseline demographics and inclusion criteria. Identified trials studied five novel anticoagulants in three each of PROBE and double-blind design. For ORs of results across studies and outcomes, there was little pattern differentiating the two designs. Among VKA-control subjects, event rates for the primary outcome (stroke or systemic embolism) in PROBE trials at 1.74 %/year (95% confidence interval: 1.54-1.95) was not significantly different from that in double-blind trials, at 1.88 (1.73-2.03). Among other outcomes, VKA-treated subjects in both trial designs had similar event rates, apart from higher all-cause mortality in ROCKET AF, and lower myocardial infarction rates among the PROBE study patients. Although there are differences in outcome between PROBE and double blind trials, they do not appear to be design-related. The exacting requirements of double-blinding in AF trials may not be necessary.

  19. 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

  20. Maintenance of response after open-label treatment with atomoxetine hydrochloride in international European and non-European adult outpatients with attention-deficit/hyperactivity disorder: a placebo-controlled, randomised withdrawal study

    Directory of Open Access Journals (Sweden)

    Himanshu Upadhyaya

    2013-09-01

    Full Text Available Background and Objectives: We evaluated maintenance of response to atomoxetine during a 25-week, double-blind, placebo-controlled, randomised withdrawal period in adults with attention-deficit/hyperactivity disorder (ADHD who previously responded to atomoxetine during a 12 week open-label treatment period and maintained that response during a 12-week double-blind maintenance period. Methods: Patients (N = 2017, 18 to 50 years of age, diagnosed with ADHD from 152 outpatient sites in 18 countries received 12 weeks of open-label atomoxetine (40-100 mg/day followed by 12 weeks of double-blind maintenance (80 or 100 mg/day. Responders were randomized to atomoxetine (N = 266 or placebo (N = 258 for 25-weeks of double-blind treatment. The percentage of patients with a reduction >30% in their baseline Conners' ADHD Rating Scale Investigator-Rated: Screening Version (CAARS-Inv:SV total score and a score of <3 on the Clinical Global Impression ADHD-Severity (CGI-ADHD-S after 25 weeks was compared between treatment groups with a Fisher's exact test. Mean changes from baseline in the CAARS-Inv:SV and Adult Attention-Deficit/Hyperactivity Disorder Quality of Life (AAQoL were analysed. Results: Most patients enrolled (60% were from Europe. More atomoxetine- than placebo-treated patients maintained a satisfactory response postrandomisation (64.3% vs. 50.0%; p < .001. Time-to-relapse was significantly longer for atomoxetine than placebo (p = .004. Atomoxetine maintained greater improvements in ADHD symptoms compared with placebo (LS mean worsening in the CAARS-Inv:SV total score was 0.9 vs. 4.8 [ p < .001 ] and in the CGI-ADHD-S rating was 0.0 vs. 0.5 [ p < .001 ]. These results were supported by self- or observer-rated measures. Lastly, atomoxetine maintained greater improvements in quality of life compared with placebo (AAQoL total score was 0.4 vs. -4.0; p = .002. Conclusions: This study demonstrated that atomoxetine was superior to placebo in maintaining

  1. Pharmacokinetic profile of rizatriptan 10-mg tablet and 10-mg orally disintegrating tablet administered with or without water in healthy subjects: an open-label, randomized, single-dose, 3-period crossover study.

    Science.gov (United States)

    Swan, Suzanne K; Alcorn, Harry; Rodgers, Anthony; Hustad, Carolyn M; Ramsey, Karen E; Woll, Susan; Skobieranda, Franck

    2006-02-01

    This open-label, 3-period crossover study compared the plasma concentration profiles of rizatriptan tablet, orally disintegrating tablet with water (ODTc), and ODT without water (ODTs) in 24 healthy volunteers aged 18 to 45 years. At each period, subjects received a single dose of either 10-mg rizatriptan tablet, 10-mg rizatriptan ODTs, or 10-mg rizatriptan ODTc. The authors hypothesized that ODTc has a greater geometric mean AUC(0-2h) than ODTs and that ODTc has a greater geometric mean AUC(0-1h) than tablet. A secondary end point was to compare the time of occurrence of the maximum rizatriptan plasma concentration (t(max)) of each dosing method. ODTc had a statistically significantly greater geometric mean AUC(0-2h) compared with ODTs (33.84 h x ng/mL vs 18.83 h x ng/mL; P rizatriptan tablet (17.07 h x ng/mL vs 13.32 h x ng/mL). The median t(max) was 0.67 hours for ODTc and tablet and 1.33 hours for ODTs. ODTc showed a slightly, but not significantly, faster rate of absorption compared with tablet. ODTs with water had a faster rate of absorption than ODTc. Future studies are needed to determine whether this pharmacokinetic difference produces differential efficacy in a clinical setting.

  2. Open-label evaluation of a novel skin brightening system containing 0.01% decapeptide-12 in combination with 20% buffered glycolic acid for the treatment of mild to moderate facial melasma.

    Science.gov (United States)

    Ramírez, Sandra P; Carvajal, Alfonso C; Salazar, Juan C; Arroyave, Gladys; Flórez, Ana M; Echeverry, Hector F

    2013-06-01

    Melasma is a cutaneous disorder that primarily affects females of Hispanic and Asian descent. Previous studies have shown that use of a brightening system comprised of 0.01% decapeptide-12 cream, an antioxidant cleanser, a 20% buffered glycolic acid lotion, and a broad spectrum SPF 30 sunscreen yields good clearance of mild-to-moderate melasma in Caucasian and Asian volunteers. The present open-label, prospective, and multicenter study sought to determine the tolerability and efficacy of the above-mentioned brightening system on mild-to-moderate melasma in 33 Hispanic females over 16 weeks. Clinical measures included self-assessment of tolerability, clinical grading, determination of Melasma Area and Severity Index (MASI) scores, and standardized clinical photography. Results showed that the system was well tolerated with no adverse events reported. Mean decreases of 36%, 46%, 54%, and 60% in MASI scores were observed at weeks 4, 8, 12, and 16, respectively, which were further corroborated by standardized photography showing visible reduction in the appearance of melasma. Results suggest that the brightening system consisting of 0.01% decapeptide-12 cream, an antioxidant cleanser, 20% buffered glycolic acid lotion, and broad spectrum SPF 30 sunscreen is safe and efficacious for the treatment of mild-to-moderate melasma in Hispanic females.

  3. 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.

  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. Pharmacokinetics and adhesion of a transdermal patch containing ethinyl estradiol and gestodene under conditions of heat, humidity, and exercise: A single-center, open-label, randomized, crossover study.

    Science.gov (United States)

    Zurth, Christian; Schuett, Barbara; Casjens, Manuela; Ludwig, Matthias; Waellnitz, Katrin

    2015-07-01

    In this open-label, randomized study, 36 women (18-45 years) applied an ethinyl estradiol/gestodene contraceptive patch once-weekly for 3 weeks followed by a 1-week, patch-free interval, in 3 treatment periods. The primary objective was to evaluate the pharmacokinetics of ethinyl estradiol and gestodene under conditions of heat, humidity, and exercise. The secondary objective was to evaluate patch adhesion under the same conditions. Weeks 1 and 2 of each period comprised "standardized normal activity" (SNA); in week 3, SNA continued or women used a sauna, whirlpool, swimming pool, or performed an exercise combination. Thirty-one women completed the study; 23 yielded evaluable pharmacokinetic data. Analyses were exploratory and conducted using an analysis of variance. Area under the concentration-time curve from 0 to 168 hours (AUC0-168 ) for gestodene and ethinyl estradiol during sauna, swimming, and whirlpool was equivalent to previous SNA recordings. For exercise combination, the gestodene AUC0-168 was 12% lower compared with SNA, albeit not considered clinically relevant. Two women lost a total of 3 patches during sporting activities; other detachments during this week were not correlated with sporting activity. Overall, hormone delivery using the ethinyl estradiol/gestodene patch under conditions of heat, humidity, and exercise corresponded to delivery under normal conditions.

  7. A 4-month, open-label study evaluating the efficacy of eflornithine 11.5% cream in the treatment of unwanted facial hair in women using TrichoScan.

    Science.gov (United States)

    Hoffmann, Rolf

    2008-01-01

    Eflornithine 11.5% cream is an effective treatment for unwanted facial hair (UFH) in women with the effect on facial hair growth starting to be seen from 1 month after treatment initiation. TrichoScan is a validated method of assessing hair length, thickness, density, and growth rate using contact skin microscopy. The study aimed to evaluate the efficacy of eflornithine cream in women with UFH, as assessed by TrichoScan. In this open-label, single-centre study, 25 women (aged 25-63 years) applied eflornithine 11.5% cream to the upper lip twice daily for 4 months. Hair density, mean and cumulative hair length, mean hair thickness and hair growth rate were assessed at baseline and Month 1, 2 and 4 using TrichoScan. Eflornithine cream significantly decreased hair density from baseline to Month 1 (- 11.4 hairs/cm2, p = 0.014), Month 2 (- 16.5 hairs/cm2, p = 0.013) and Month 4 (- 12.05 hairs/cm2, p = 0.05). In addition, cumulative hair length decreased from baseline to Month 1 (- 7.104 mm, p = 0.001), Month 2 (- 10.054 mm, p hair growth rate. Mean hair thickness did not change significantly. Eflornithine 11.5% cream is an effective treatment for UFH in women with the effect on facial hair growth starting to be seen from 1 month after treatment initiation.

  8. Lapatinib versus hormone therapy in patients with advanced renal cell carcinoma: a randomized phase III clinical trial

    DEFF Research Database (Denmark)

    Ravaud, Alain; Hawkins, Robert; Gardner, Jason P;

    2008-01-01

    PURPOSE: Lapatinib is an orally reversible inhibitor of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER-2) tyrosine kinases with demonstrated activity in patients with HER-2-positive breast cancer. In the current phase III open-label trial, lapatinib was comp...

  9. 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 syndro...

  10. Effects of a structured 20-session slow-cortical-potential-based neurofeedback program on attentional performance in children and adolescents with attention-deficit hyperactivity disorder: retrospective analysis of an open-label pilot-approach and 6-month follow-up

    Science.gov (United States)

    Albrecht, Johanna S; Bubenzer-Busch, Sarah; Gallien, Anne; Knospe, Eva Lotte; Gaber, Tilman J; Zepf, Florian D

    2017-01-01

    obtained preliminary data are the rather small sample size, the lack of a control group/a placebo condition and the open-label approach because of the clinical setting and retrospective analysis. The value of the current approach lies in providing pilot data for future studies involving larger samples. PMID:28293109

  11. 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

  12. 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

  13. Efficacy and safety of a once-daily extended-release formulation of pramipexole switched from an immediate-release formulation in patients with advanced Parkinson's disease: results from an open-label study.

    Science.gov (United States)

    Takanashi, M; Shimo, Y; Hatano, T; Oyama, G; Hattori, N

    2013-12-01

    This study aimed to evaluate the efficacy and safety of an extended-release tablet formulation of pramipexole (PPX-ER) given once daily when switched from an immediate-release tablet formulation (PPX-IR) given 3 times daily. This open-label study included 29 patients with idiopathic Parkinson's disease (PD) who were followed for 8 weeks. Primary endpoints were Unified Parkinson's Disease Rating Scale (UPDRS) part III score, a physician evaluation of motor symptoms; nocturnal and early morning symptoms (NEMS) score, based on the results for 4 items in the Parkinson's Disease Sleep Scale and the Movement Disorder Society - sponsored revision of the UPDRS; and patients' formulation preference, determined through questionnaires. Secondary endpoints were nocturnal sleep disturbance, evaluated using the revised version of the Parkinson's Disease Sleep Scale (PDSS-2); quality of life, evaluated using the 39-item Parkinson's Disease Questionnaire (PDQ-39); Clinical Global Impression-Improvement (CGI-I) score; Patient Global Impression-Improvement (PGI-I) score; and caregiver formulation preference. UPDRS part III score (mean ± SD) was significantly decreased after 4 weeks (13.9 ± 7.3; P=0.030) and 8 weeks (12.2 ± 7.3; P<0.001) from baseline (15.3 ± 7.0). However, no significant change was found in NEMS scale, PDSS-2 or PDQ-39 scores. After 8 weeks, the responder rates based on CGI-I and PGI-I scores were 27.6% and 20.7%, respectively. As a result of the questionnaire, 63.0% of patients and 58.8% of their caregivers preferred PPX-ER. A non-serious drug-related adverse event (diarrhea) was observed in one patient. In conclusion, PPX-ER can be considered as a useful treatment option when PPX-IR needs to be switched to other dopamine agonists.This study is registered with UMIN-CTR (UMIN000006521).

  14. Sustained effects of once-daily memantine treatment on cognition and functional communication skills in patients with moderate to severe Alzheimer's disease: results of a 16-week open-label trial.

    Science.gov (United States)

    Schulz, Jörg B; Rainer, Michael; Klünemann, Hans-Hermann; Kurz, Alexander; Wolf, Stefanie; Sternberg, Kati; Tennigkeit, Frank

    2011-01-01

    The present study evaluated the effects of once-daily memantine (20 mg) treatment on cognition and communication in patients with moderate to severe Alzheimer's disease (AD). In a multicenter, single-arm open-label study, outpatients diagnosed with AD (MMSE < 20; n = 97) were titrated from 5 mg to 20 mg once-daily memantine over 4 weeks. Once-daily memantine treatment (20 mg) was then continued for 8 weeks, followed by a 4-week wash-out period. The primary efficacy endpoint was the change from baseline in the Consortium to Establish a Registry for Alzheimer's Disease -Neuropsychological Battery (CERAD-NP) total score. Secondary efficacy endpoints included change from baseline in Functional Communication Language Inventory (FLCI) and ADCS-ADL19 total score, and the response from baseline in Clinical Global Impression of Change (CGI-C). The CERAD-NP total score improved significantly after 12 weeks of once-daily memantine treatment compared with baseline (5.9 ± 8.8; p < 0.0001). The FLCI total score improved significantly after 12 weeks compared with baseline (4.4 ± 6.8; p < 0.0001). These significant improvements were already observed after 4 and 8 weeks of once-daily memantine treatment and persisted after a 4-week wash-out period. ADCS-ADL19 total scores showed only slight increases from baseline, and CGI-C indicated that the majority of patients experienced an improvement or stabilization of the disease after 12 weeks. At least one Treatment-Emergent Adverse Event was reported by 38 (39.2%) patients. In patients with moderate to severe AD, once-daily memantine (20 mg) treatment significantly improved cognition and functional communication and was found to have a favorable safety and tolerability profile.

  15. Efficacy and safety of canagliflozin alone or as add-on to other oral antihyperglycemic drugs in Japanese patients with type 2 diabetes: A 52-week open-label study

    Science.gov (United States)

    Inagaki, Nobuya; Kondo, Kazuoki; Yoshinari, Toru; Kuki, Hideki

    2015-01-01

    Aims/Introduction Canagliflozin is a sodium–glucose cotransporter 2 inhibitor under development for the treatment of type 2 diabetes. Our aim was to examine its efficacy and safety as monotherapy or in combination with commonly used oral antihyperglycemic drugs in Japanese patients with type 2 diabetes. Materials and Methods Patients on diet/exercise alone or diet/exercise plus an oral antihyperglycemic drug (sulfonylurea, glinide, α-glucosidase inhibitor, biguanide, thiazolidinedione or dipeptidyl peptidase-4 inhibitor) were randomized to either 100 or 200 mg canagliflozin while continuing prior therapy. Patients were treated for 52 weeks in an open-label manner. Results Canagliflozin significantly reduced hemoglobin A1c, fasting plasma glucose and bodyweight in all the study groups. Improvements were apparent by 4 weeks of treatment, and were maintained for 52 weeks. The reduction in hemoglobin A1c ranged from −0.80 to −1.06%, and from −0.93 to −1.26% in the 100 and 200 mg canagliflozin groups, respectively. Drug-related adverse events occurred in approximately one-third of patients, and included hypoglycemia/asymptomatic hypoglycemia and pollakiuria. Hypoglycemia/asymptomatic hypoglycemia was most common in patients treated with a sulfonylurea. Most adverse events were classified as mild or moderate in severity. Conclusions The results of the present study confirmed that treatment with canagliflozin resulted in significant reductions in glycemic control and bodyweight that were maintained for 52 weeks of treatment irrespective of whether it was administered as monotherapy or in combination with another oral antihyperglycemic drug. Canagliflozin was well tolerated, with a low incidence of drug-related adverse events. This trial was registered with ClinicalTrials.gov (no. NCT01387737). PMID:25802729

  16. 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

  17. 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)

  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. Efficacy and safety of a recombinant factor IX (Bax326) in previously treated patients with severe or moderately severe haemophilia B undergoing surgical or other invasive procedures: a prospective, open-label, uncontrolled, multicentre, phase III study.

    Science.gov (United States)

    Windyga, J; Lissitchkov, T; Stasyshyn, O; Mamonov, V; Ghandehari, H; Chapman, M; Fritsch, S; Wong, W-Y; Pavlova, B G; Abbuehl, B E

    2014-09-01

    Haemostatic management of haemophilia B patients undergoing surgery is critical to patient safety. The aim of this ongoing prospective trial was to investigate the haemostatic efficacy and safety of a recombinant factor IX (rFIX) (Bax326) in previously treated subjects (12-65 years, without history of FIX inhibitors) with severe or moderately severe haemophilia B, undergoing surgical, dental or other invasive procedures. Haemostatic efficacy was assessed according to a predefined scale. Blood loss was compared to the average and maximum blood loss predicted preoperatively. Haemostatic FIX levels were achieved peri- and postoperatively in 100% of subjects (n = 14). Haemostasis was 'excellent' intraoperatively in all patients and postoperatively in those without a drain, and 'excellent' or 'good' at the time of drain removal and day of discharge in those with a drain employed. Following the initial dose, the mean FIX activity level rose from 6.55% to 107.58% for major surgeries and from 3.60% to 81.4% for minor surgeries. Actual vs. predicted blood loss matched predicted intraoperative blood loss but was equal to or higher than (but less than 150%) the maximum predicted postoperative blood loss reflecting the severity of procedure and FIX requirements. There were no related adverse events, severe allergic reactions or thrombotic events. There was no evidence that BAX326 increased the risk of inhibitor or binding antibody development to FIX. BAX326 was safe and effective for peri-operative management of 14 subjects with severe and moderately severe haemophilia B.

  20. 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.

  1. 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.

    Science.gov (United States)

    Badar, Talha; Cortes, Jorge; Borthakur, Gautam; O'Brien, Susan; Wierda, William; Garcia-Manero, Guillermo; Ferrajoli, Alessandra; Kadia, Tapan; Poku, Rebeca; Kantarjian, Hagop; Mattiuzzi, Gloria

    2015-01-01

    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.

  2. 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.

  3. 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

  4. 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

    in >10% of patients, regardless of relationship to study drug were thrombocytopenia (94%), anemia (84%), neutropenia (61%), leukopenia (42%), pyrexia (36%), asthenia (32%), fatigue and nausea (26%), bone pain (19%), cough, diarrhea, dyspnea, mucosal inflammation and upper respiratory infection (16...

  5. 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

  6. Phase I/II open-label study of the biologic effects of the interleukin-2 immunocytokine EMD 273063 (hu14.18-IL2 in patients with metastatic malignant melanoma

    Directory of Open Access Journals (Sweden)

    Gillies Stephen D

    2009-07-01

    Full Text Available Abstract Background To explore the biological activity of EMD 273063 (hu14.18-IL2, a humanized anti-GD2 monoclonal antibody fused to interleukin-2 (IL2, in patients with unresectable, stage IV cutaneous melanoma as measured by induction of immune activation at the tumor site and in peripheral blood. Methods Nine patients were treated with 4 mg/m2 per day of EMD 273063 given as a 4-h intravenous infusion on days 1, 2, and 3 every four weeks (one cycle. Peripheral blood was analyzed for T cell and natural killer cell phenotype and frequency, as well as levels of soluble IL2 receptor (sIL2R, IL10, IL6, tumor necrosis factor alpha and neopterin. Biopsies of tumor metastasis were performed prior to therapy and at day 10 of the first 2 cycles to study lymphocyte accumulation by immunohistochemistry. Results Treatment was generally well tolerated and there were no study drug-related grade 4 adverse events. Grade 3 events were mainly those associated with IL2, most commonly rigors (3 patients and pyrexia (2 patients. Best response on therapy was stable disease in 2 patients. There were no objective tumor regressions by standard response criteria. Systemic immune activation was demonstrated by increases in serum levels of sIL2R, IL10, and neopterin. There was evidence of increased tumor infiltration by T cells, but not NK cells, in most post-dosing biopsies, suggesting recruitment of immune cells to the tumor site. Conclusion EMD 273063 demonstrated biologic activity with increased immune-related cytokines and intratumoral changes in some patients consistent with the suspected mechanism of action of this immunocytokine.

  7. 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

  8. 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

  9. 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

    BACKGROUND: Patients with muscle-invasive urothelial carcinoma of the bladder have poor survival after cystectomy. The EORTC 30994 trial aimed to compare immediate versus deferred cisplatin-based combination chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcin...... patient data meta-analysis and biomarker research are needed to further elucidate the potential for survival benefit in subgroups of patients. FUNDING: Lilly, Canadian Cancer Society Research.......BACKGROUND: Patients with muscle-invasive urothelial carcinoma of the bladder have poor survival after cystectomy. The EORTC 30994 trial aimed to compare immediate versus deferred cisplatin-based combination chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial......, doxorubicin, and cisplatin [high-dose MVAC], or MVAC) or six cycles of deferred chemotherapy at relapse, with stratification for institution, pT category, and lymph node status according to the number of nodes dissected. Neither patients nor investigators were masked. Overall survival was the primary endpoint...

  10. 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

    OpenAIRE

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

    2015-01-01

    abstract 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 ch...

  11. 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

    2016-03-03

    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 vaccine. DTPa-IPV/Hib conjugate vaccine was well tolerated as a booster dose in healthy Vietnamese children aged <2 years.

  12. 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

  13. 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

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

    Directory of Open Access Journals (Sweden)

    E. S. Tsvetkova

    2016-01-01

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

  15. 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

  16. 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

  17. 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

  18. Effect of a new insulin treatment regimen on glycaemic control and quality of life of Muslim patients with type 2 diabetes mellitus during Ramadan fast - an open label, controlled, multicentre, cluster randomised study.

    Science.gov (United States)

    Shehadeh, N; Maor, Y

    2015-11-01

    We performed a non-inferiority trial comparing insulin detemir (Levemir) and biphasic insulin (NovoMix70) to standard care during Ramadan fast in insulin treated type 2 diabetes mellitus (T2DM) patients. This was an open label, controlled, multicentre, cluster randomised non-inferiority study. Insulin treated T2DM patients from 12 randomly selected primary clinics received Levemir and NovoMix 70 (intervention, n = 127) or standard care according to the American Diabetes Association recommendations (control, n = 118). Insulin dose (intervention) was 60% of the usual, of this 40% was dosed as Levemir at sunrise and 60% as NovoMix 70 before dinner. Insulin was titrated according to daily 4 point self-measured blood glucose (4P-SMBG) levels. The primary outcome was the difference in mean daily 4P-SMBG during days 23-30 of treatment. Mean age was 60.1 (SD 8.9) and 59.4 (SD 10.1) years in the intervention and control respectively. Mean HbA1c was 8.38% (68 mmol/mol) (SD 0.96) and 8.45% (69 mmol/mol) (SD 1.08). Mean BMI was 32.99 (SD 7.05) and 33.08 (SD 7.24), respectively. The intervention was non-inferior to standard care as assessed by mean 4P-SMBG during days 23-30 of treatment [155 (SD 30.76) mg% and 159 (SD 33.24) mg% respectively, p = 0.269]. Adverse event rate was significantly lower in the intervention group [0.04 (SD 0.06) vs. 0.07 (SD 0.11), p = 0.010]. In particular, hypoglycaemia event rate was lower in the intervention group [0.00 (SD 0.01) vs. 0.01 (SD 0.03), p ≤ 0.001]. To conclude, treatment with Levemir and NovoMix 70 was non-inferior to standard care in this heterogeneous group of patients and was associated with less adverse events.

  19. 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

  20. 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.

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

    Science.gov (United States)

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

    2015-01-01

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

  2. 米非司酮配伍米索前列醇终止16~24周妊娠的随机对照研究%Mifepristone combined with misoprostol in terminating 16- 24 weeks gestation: a randomized controlled study

    Institute of Scientific and Technical Information of China (English)

    花琪; 程丽村; 范晓芳; 张岚蓉; 陈勤芳

    2011-01-01

    目的 比较米非司酮配伍米索前列醇与羊膜腔内依沙吖啶注射终止16~24周妊娠的临床效果,为制定米非司酮配伍米索前列醇终止16~24周妊娠的用药常规提供临床依据.方法 根据计算机产生的随机数字表,将629例随机分配为米非司酮配伍米索前列醇组(米非米索组,310例)和羊膜腔内依沙吖啶注射组(依沙吖啶组,319例).两组均于胎儿、胎盘娩出后24 h常规行B超检查后清宫.结果 两组引产成功率分别为93.2%(289/310)和95.6%(305/319),差异无统计学意义(P>0.05).米非米索组胎儿娩出的时间为(12.0±5.9)h,显著短于依沙吖啶组的(45.2士14.1)h(P<0.001).米非米索组引产后24 h内出血量为(113.5±69.5)mL,显著少于依沙吖啶组的(146.0±70.5)mL(P<0.05).结论 米非司酮配伍米索前列醇终止16~24周妊娠安全、有效.%Objective To compare the clinical efficacies of mifepristone combined with misoprostol with ethacridine in terminating 16-24 weeks gestation, so as to provide clinical evidence for routine use of mifepristone plus misoprostol for termination of 16-24 weeks of gestation. Methods A total of 629 healthy pregnant women requiring induced abortion in 16-24 weeks gestation were randomly divided into mifepristone group (mifepristone 200 mg po, misopmstol 400 μg PV) and ethacridine group (intra-amniotic injection of ethacridine 100 mg). The patients in both groups received routine B- ultrasound examination and curettage 24 hours after delivery. Results The success rate of labor induction were 93.2% and 95.6% in the two groups, with no significant difference between two groups (P>0.05). There was significant difference in the induction time between the two groups (mifepristone group [12. 0 ± 5. 9] h, ethacridine group [45. 2 ± 14. 1] h, P<0. 001). The blood loss in mifepristone group was ( 113.5± 69.5) mL, which was significantly less than that in the ethacridine group within 24 hours after

  3. 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...

  4. Effects of a 250-mL enema containing sodium phosphate on electrolyte concentrations in healthy volunteers: An open-label, randomized, controlled, two-period, crossover clinical trial*

    Science.gov (United States)

    Sédaba, Belén; Azanza, Josh R.; Campanero, Miguel A.; Garcia-Quetglas, Emilio; Muñoz, Maria Josh; Marco, Santiago

    2006-01-01

    Background: Enemas are used by individuals with constipation and are often required before certain medical diagnostic procedures and surgical interventions. However, abnormalities in serum electrolyte concentrations have been associated with enema use. Objective: The aim of this study was to determine the changes in serum electrolyte concentrations (phosphorus, calcium, sodium, and potassium) and urinary phosphorus elimination after the administration of a sodium phosphate enema. Methods: Healthy volunteers aged 35 to 70 years were eligible for this open-label, randomized, controlled, 2-period, crossover clinical trial at the Clinical Research Unit of the University Hospital of Navarra, Pamplona, Spain. The study comprised 2 one-day periods separated by a 7-day washout. All subjects were randomly assigned in a 1:1 ratio to 1 of 2 study sequences: (1) a single dose of Enema Casen® 250 mL in the first period followed by no treatment (control) in the second period, or (2) no treatment in the first period followed by a single dose of the study drug in the second period. The sequence of treatment was assigned using a randomization table that was prepared before the beginning of the study. Serum concentrations of phosphorus, sodium, potassium, and calcium were measured in both periods. Urinary phosphorus elimination was measured for 12 hours after enema administration (Ae0–12) in a subset of the subjects in the second period. Adverse events (AEs) were monitored by the investigators throughout the study. Normal ranges for the electrolytes were as follows: phosphorus, 2.5 to 5 mg/dL; calcium, 8.5 to 10.5 mg/dL; sodium, 135 to 145 mEq/L; and potassium, 3.5 to 5 mEq/L. Results: Twenty-four subjects (12 men, 12 women; mean [SD] age, 47.8 [9.6] years [range, 36–68 years]) participated in the study. All of the subjects were white and none were smokers. Twelve hours after enema administration, mean serum phosphorus and sodium concentrations increased by a mean of 1.18 mg

  5. 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

  6. 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

  7. 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

  8. 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

  9. 男性勃起功能障碍的治疗偏好研究:韩国男性使用西地那非转为他达拉非的开放性研究%Treatment preferences in men with erectile dysfunction: an open label study in Korean men switching from sildenafil citrate to tadalafi

    Institute of Scientific and Technical Information of China (English)

    T. Y. Ahn; T. Dwight; M.-S. L. Lee; S. W. Lee; S.-W. Kim; D. Y. Yang; N. C. Park; K.-S. Min; K. Park; J.-S. Paick; Y. Dyachkova

    2007-01-01

    目的:评价病人对西地那非或他达拉非(PDE-5抑制剂,用来治疗 ED)的偏好性并评定这种偏好性可能的原因.方法:参与开放性研究的韩国男性在研究之前服用西地那非治疗ED至少6周.此后病人继续服用西地那非4周,之后停药1周,改服用他达拉非8周,然后在外延期选择性服药来进行治疗.通过心理和人际关系等级(PAIRS)来评定心理因素(时间关注、自发性、性自信度),根据病人日记来评定用药的时间情况.结果:研究包括160名韩国男性(平均年龄55岁),之前服用西地那非585天,在外延期有73.7%的病人选用他达拉非,而只有26.3%的病人选用西地那非(P<0.001).由西地那非改用他达拉非后,平均的PAIRS时间关注分值由2.54下降到2.42(P=0.002),在性自发性和自信度上两组病人没有显著差异.服用西地那非的病人在服药后性尝试>4小时到≤36小时的占4.5%,而服用他达拉非的病人的占17.5%.结论:在使用西地那非和他达拉非后,大部分病人偏好他达拉非.这种偏好可能受心理因素的影响,例如降低时间关注、增加性行为机会等.%Aim: To evaluate patient preferences for sildenafil citrate or tadalafil (PDE-5 inhibitors available for the treatment of erectile dysfunction [ED]) and assess potential reasons for these preferences. Methods: This open-label study was conducted on Korean men taking sildenafil, at least 6 weeks prior to study entry, for ED. Following screening,patients continued sildenafil treatment for 4 weeks, then after a 1-week washout period, switched to tadalafil for 8 weeks. Patients then continued with their treatment of choice during an extension phase. Psychosocial factors(time concern, spontaneity, sexual self-confidence) were evaluated using Psychological and Interpersonal Relationship Scales (PAIRS), while timing of dose to sexual attempt patterns were assessed from patient diaries. Results:The present study enrolled

  10. Efficacy and safety study of termination pregnancy (16 -24 weeks)useing mifepristone combined misoprostol%米非司酮联合米索前列醇终止16~24周妊娠疗效及安全性研究

    Institute of Scientific and Technical Information of China (English)

    董徐男; 郭伟平

    2015-01-01

    目的:探讨米非司酮联合米索前列醇终止16~24周妊娠的疗效和安全性。方法:将我院收治的孕龄16~24周要求终止妊娠的孕妇50例作为研究对象进行回顾性分析,其中口服给药患者23例,阴道给药患者27例。比较两组患者的总有效率、引产时间、产后出血量、阴道出血时间及米索前列醇使用剂量等有无差别。结果:口服给药组完全流产15例,不全流产7例,无效1例,清宫率为64%,总有效率为96%;阴道给药组完全流产17例,不全流产10例,无效0例,清宫率为56%,总有效率为100%,两组清宫率、总有效率比较差异无统计学意义(P>0.05)。阴道给药组患者引产时间(P0.05)。两组患者不良反应发生率差别无统计学意义(P0.05). The side effects between the two groups were not statistically different (P<0.05).ConclusionMifepristone and misoprostol could be effective and safe in the treatment of terminate pregnancies of 16-24 weeks, but administration in intravaginally was better than that of orally.

  11. Subgroup analysis of phase 3 studies of dulaglutide in Japanese patients with type 2 diabetes.

    Science.gov (United States)

    Onishi, Yukiko; Oura, Tomonori; Nishiyama, Hiroshi; Ohyama, Sumika; Takeuchi, Masakazu; Iwamoto, Noriyuki

    2016-01-01

    The efficacy and tolerability of once weekly dulaglutide 0.75 mg in Japanese patients with type 2 diabetes (T2D) were evaluated by subgroups defined by key demographic characteristics. This post hoc analysis included data from patients who received dulaglutide 0.75 mg for up to 26 weeks in three phase 3 trials (one open-label, randomized; one double-blind and open-label, randomized; one open-label, nonrandomized). Patients were classified into subgroups on the basis of sex (male, female), age (8.5%), use of concomitant sulfonylurea (yes, no), and use of concomitant biguanide (yes, no). Efficacy measures analyzed were changes from baseline in HbA1c and body weight and percentages of patients achieving HbA1c biguanides. Concomitant use of sulfonylureas had the greatest effect on the incidence of hypoglycemia. Treatment of T2D with once weekly dulaglutide 0.75 mg for 26 weeks was associated with significant improvement in glycemic control irrespective of age, sex, duration of diabetes, body weight, BMI, or concomitant medication.

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

    OpenAIRE

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

    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,...

  13. Efficacy, Safety, and Dose of Pafuramidine, a New Oral Drug for Treatment of First Stage Sleeping Sickness, in a Phase 2a Clinical Study and Phase 2b Randomized Clinical Studies.

    Directory of Open Access Journals (Sweden)

    Christian Burri

    2016-02-01

    Full Text Available Sleeping sickness (human African trypanosomiasis [HAT] is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT.The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC] between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2, where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a or 3 months (Phase 2b after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent.Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93% than pafuramidine treatment for 5 days (25% and 10 days (57%. These results support continuation of the development program for pafuramidine into Phase 3.

  14. Efficacy and Safety of AmBisome in Combination with Sodium Stibogluconate or Miltefosine and Miltefosine Monotherapy for African Visceral Leishmaniasis: Phase II Randomized Trial.

    OpenAIRE

    Wasunna, M; Njenga, S; Balasegaram, M.; Alexander, N; Omollo, R; Edwards, T.; Dorlo, TP; Musa, B; Ali, MH; Elamin, MY; Kirigi, G; Juma, R; Kip, AE; Schoone, GJ; Hailu, A.

    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...

  15. Efficacy and Safety of AmBisome in Combination with Sodium Stibogluconate or Miltefosine and Miltefosine Monotherapy for African Visceral Leishmaniasis: Phase II Randomized Trial

    OpenAIRE

    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; Juma, Rashid; Kip, Anke E; Schoone, Gerard J.; Hailu, Asrat

    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 t...

  16. 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.

  17. An exploratory, randomized, parallel-group, open-label, relative bioavailability study with an additional two-period crossover food-effect study exploring the pharmacokinetics of two novel formulations of pexmetinib (ARRY-614

    Directory of Open Access Journals (Sweden)

    Wollenberg LA

    2015-09-01

    Full Text Available Lance A Wollenberg,1 Donald T Corson,2,3 Courtney A Nugent,1 Farran L Peterson,1 Ann M Ptaszynski,1 Alisha Arrigo,2,3 Coralee G Mannila,2,3 Kevin S Litwiler,1 Stacie J Bell1,4 1Array BioPharma, Boulder, 2Array BioPharma, Longmont, CO, 3Avista Pharma Solutions, Longmont, CO, 4Mallinckrodt Pharmaceuticals, Ellicott City, MD, USA Background: Pexmetinib (ARRY-614 is a dual inhibitor of p38 mitogen-activated protein kinase and Tie2 signaling pathways implicated in the pathogenesis of myelodysplastic syndromes. Previous clinical experience in a Phase I dose-escalation study of myelodysplastic syndrome patients using pexmetinib administered as neat powder-in-capsule (PIC exhibited high variability in pharmacokinetics and excessive pill burden, prompting an effort to improve the formulation of pexmetinib. Methods: A relative bioavailability assessment encompassed three parallel treatment cohorts of unique subjects comparing the two new formulations (12 subjects per cohort, a liquid oral suspension (LOS and liquid-filled capsule (LFC and the current clinical PIC formulation (six subjects in a fasted state. The food-effect assessment was conducted as a crossover of the LOS and LFC formulations administered under fed and fasted conditions. Subjects were divided into two groups of equal size to evaluate potential period effects on the food-effect assessment. Results: The geometric mean values of the total plasma exposures based upon area-under-the-curve to the last quantifiable sample (AUClast of pexmetinib were approximately four- and twofold higher after administration of the LFC and LOS formulations, respectively, than after the PIC formulation, when the formulations were administered in the fasted state. When the LFC formulation was administered in the fed state, pexmetinib AUClast decreased by <5% compared with the fasted state. After administration of the LOS formulation in the fed state, pexmetinib AUClast was 34% greater than observed in the fasted

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

    OpenAIRE

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

    2015-01-01

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

  19. 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.

  20. Modulation of Autoimmune T-Cell Memory by Stem Cell Educator Therapy: Phase 1/2 Clinical Trial

    OpenAIRE

    Elias Delgado; Marcos Perez-Basterrechea; Beatriz Suarez-Alvarez; Huimin Zhou; Eva Martinez Revuelta; Jose Maria Garcia-Gala; Silvia Perez; Maria Alvarez-Viejo; Edelmiro Menendez; Carlos Lopez-Larrea; Ruifeng Tang; Zhenlong Zhu; Wei Hu; Thomas Moss; Edward Guindi

    2015-01-01

    Background: Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that causes a deficit of pancreatic islet β cells. The complexities of overcoming autoimmunity in T1D have contributed to the challenges the research community faces when devising successful treatments with conventional immune therapies. Overcoming autoimmune T cell memory represents one of the key hurdles. Methods: In this open-label, phase 1/phase 2 study, Caucasian T1D patients (N = 15) received two treatments wit...

  1. 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 deferasirox was well tolerated and effective in reducing iron burden in patients with hereditary hemochromatosis and could be a safe alternative to phlebotomy in selected patients.

  2. Recombinant human interleukin-1 receptor antagonist in severe traumatic brain injury: a phase II randomized control trial

    OpenAIRE

    Helmy, Adel; Guilfoyle, Mathew R.; Carpenter, Keri LH; Pickard, John D.; Menon, David K.; Hutchinson, Peter J.

    2014-01-01

    Traumatic brain injury (TBI) is the commonest cause of death and disability in those aged under 40 years. Interleukin-1 receptor antagonist (IL1ra) is an endogenous competitive antagonist at the interleukin-1 type-1 receptor (IL-1R). Antagonism at the IL-1R confers neuroprotection in several rodent models of neuronal injury (i.e., trauma, stroke and excitotoxicity). We describe a single center, phase II, open label, randomized-control study of recombinant human IL1ra (rhIL1ra, anakinra) in se...

  3. 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

  4. 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.

  5. 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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  7. 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

  8. 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

  9. 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

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

    Institute of Scientific and Technical Information of China (English)

    田季雨; 黄远桂; 胡安恒; 马磊; 尹庆春; 蔡艺灵

    2008-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  12. 西罗莫司在肾移植术后早期计划性切换的前瞻性对照研究%Early conversion from calcineurin inhibitor to sirolimusto after renal transplantation:a prospective,open-label and non-randomized control study

    Institute of Scientific and Technical Information of China (English)

    黄洪锋; 谢文卿; 吴建永; 徐莹; 余献平; 任萍萍; 陈江华

    2014-01-01

    Objective To explore the efficacy and safety of designed early conversion from calcineurin inhibitor (CNI) to sirolimus (SRL) as major immunosuppressive therapy in renal transplant recipients with stable renal function.Methods A prospective,open-label and non-randomized control study was performed for 112 renal transplant recipients (3-6 months post-operation) with stable renal function between June 2008 and June 2011.The patients in SRL group (n =57) switched to sirolimus while those in CNI group (n =55) continued CNI.The dosing of mycophenolate mofetil and steroids had no change.They were followed up for at least 24 months to evaluate the acute rejection,patient and graft survival,renal function,estimated glomerular filtration rate (eGFR),blood lipids,blood glucose,liver function and urinary protein at 1,6,12 and 24 months after inclusion.Adverse events were also recorded.Results The serum creatinine of SRL group decreased significantly after conversion ((89.2 ± 24.7),(87.6 ± 23.8),(86.1 ±20.4),(86.7 ± 19.7) vs(117.0 ± 16.3) μ.mol/L,all P < 0.05).CNI group showed no improvement of renal function.SRL group had a significantly higher eGFR than CNI group (P < 0.05).Among 3 cases of acute rejection,there were 2 in SRL group and 1 in CNI group (P > 0.05).Blood lipids in SRL group increased significantly at 1 month after conversion (P < 0.05) and reverted back to average level after intervention (P > 0.05).SRL group had a drop of hemoglobin level within the normal range.Two patients in SRL group developed hypokalemia and another 2 patients had oral ulcer.They all improved after treatment.During follow-ups,1 case of mild proteinuria was found in SIR group.Three patients were diagnosed with diabetes (1 in SRL group vs 2 in CNI group).Conclusions Early conversion from CNI to SRL as major immunosuppressive therapy in renal transplant recipients with stable renal function further improves renal function.There is no higher rate of acute rejection during

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  14. 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.

  15. Phases and Phase Transitions

    Science.gov (United States)

    Gitterman, Moshe

    2014-09-01

    In discussing phase transitions, the first thing that we have to do is to define a phase. This is a concept from thermodynamics and statistical mechanics, where a phase is defined as a homogeneous system. As a simple example, let us consider instant coffee. This consists of coffee powder dissolved in water, and after stirring it we have a homogeneous mixture, i.e., a single phase. If we add to a cup of coffee a spoonful of sugar and stir it well, we still have a single phase -- sweet coffee. However, if we add ten spoonfuls of sugar, then the contents of the cup will no longer be homogeneous, but rather a mixture of two homogeneous systems or phases, sweet liquid coffee on top and coffee-flavored wet sugar at the bottom...

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

    Science.gov (United States)

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

    2003-11-01

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

  17. 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.

  18. 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...... endpoint was the mean change in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) total score from baseline to week 12. Secondary efficacy endpoints included remission (defined as Y-BOCS total score

  19. Efalizumab in the Treatment of Scalp, Palmoplantar and Nail Psoriasis: Results of a 24-Week Latin American Study

    OpenAIRE

    Takahashi, María Denise; Chouela, Edgardo Néstor; Dorantes, Gladys Leon; ROSELINO, Ana Maria; Santamaria, Jesùs; Allevato, Miguel Angel; Cestari, Tania; de Aillaud, Maria Eugenia Manzanera; Stengel, Fernando Miguel; Licu, Daiana

    2010-01-01

    Introduction Plaque-type psoriasis affecting the nails, scalp, hands or feet can often be difficult to treat; for example, topical treatments and phototherapy may not penetrate the nail plate or scalp. The objective of this large, international, multicentre study was to investigate the efficacy of efalizumab in a Latin American population of adult patients with moderate-to-severe chronic plaque psoriasis who were candidates for systemic therapy or phototherapy. Methods Eligible patients were ...

  20. 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

  1. A phase Ⅳ, open-label, randomized, multiple-center, parallel study on compare the emergence time and quality of sevoflurane versus isoflurane used as maintenance anesthetics in 2 to 3 hours surgical procedures%七氟醚用于成人全身吸入麻醉的随机、开放、多中心、阳性对照临床研究

    Institute of Scientific and Technical Information of China (English)

    吴新民; 叶铁虎; 于布为; 邓小明; 黄文起; 梁伟民; 缪长虹; 米卫东; 王保国; 王俊科; 吴安石

    2007-01-01

    目的 评估七氟醚和异氟醚全身麻醉后的苏醒时间及其安全性.方法 前瞻性、开放、随机、多中心、异氟醚平行对照临床研究,222例手术时需要全身麻醉、气管插管、预计手术持续时间在2~3 h之间的成年择期手术患者,按1:1随机入组接受七氟醚或异氟醚吸入麻醉.评估苏醒时间、拔管时间、改良Aldrete评分达到9分时间、苏醒时间和麻醉药用量之间的关系.根据生命体征、记录的不良事件评价其安全性.结果 222例患者中220例完成全部研究过程,其中七氟醚组111例,异氟醚组109例.与异氟醚组相比,七氟醚组苏醒时间缩短5.4 min、改良Aldrete评分达到9分时间缩短8.4 min、拔管时间缩短4.6 min(P<0.01).两组苏醒时间与麻醉药用量之间均具有相关性,即麻醉药用量越大苏醒时间越长.七氟醚组发生的不良事件均为轻度或中度,且不良事件类型和发生率与异氟醚组相似.结论 七氟醚全麻恢复效果优于异氟醚,且安全性和耐受性良好.

  2. A phase 3 randomized trial comparing inolimomab vs usual care in steroid-resistant acute GVHD.

    Science.gov (United States)

    Socié, Gérard; Vigouroux, Stéphane; Yakoub-Agha, Ibrahim; Bay, Jacques-Olivier; Fürst, Sabine; Bilger, Karin; Suarez, Felipe; Michallet, Mauricette; Bron, Dominique; Gard, Philippe; Medeghri, Zakaria; Lehert, Philippe; Lai, Chinglin; Corn, Tim; Vernant, Jean-Paul

    2017-02-02

    Treatment of steroid-resistant acute graft-versus-host disease (GVHD) remains an unmet clinical need. Inolimomab, a monoclonal antibody to CD25, has shown encouraging results in phase 2 trials. This phase 3 randomized, open-label, multicenter trial compared inolimomab vs usual care in adult patients with steroid-refractory acute GVHD. Patients were randomly selected to receive treatment with inolimomab or usual care (the control group was treated with antithymocyte globulin [ATG]). The primary objective was to evaluate overall survival at 1 year without changing baseline allocated therapy. A total of 100 patients were randomly placed: 49 patients in the inolimomab arm and 51 patients in the ATG arm. The primary criteria were reached by 14 patients (28.5%) in the inolimomab and 11 patients (21.5%) in the ATG arms, with a hazard ratio of 0.874 (P = .28). With a minimum follow-up of 1 year, 26 (53%) and 31 (60%) patients died in the inolimomab and ATG arms, respectively. Adverse events were similar in the 2 arms, with fewer viral infections in the inolimomab arm compared with the ATG arm. The primary end point of this randomized phase 3 trial was not achieved. The lack of a statistically significant effect confirms the need for development of more effective treatments for acute GVHD. This trial is registered to https://www.clinicaltrialsregister.eu/ctr-search/search as EUDRACT 2007-005009-24.

  3. 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

    .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......./kg). Clinical assessment included skin sclerosis score, scleroderma health assessment questionnaire, self-reported functional score and physician global visual analogue scale. Collagen turnover, skin biopsy analysis and full safety evaluation were performed. RESULTS: There was no significant change in skin...... score at 26 weeks but a trend for lower modified Rodnan skin score at 22 weeks (OR 17, 95% CI 6 to 46) compared with peak value (OR 29, 95% CI 11 to 44; p = 0.10). Serum aminoterminal propeptide of type III collagen level was significantly lower at week 26 compared with baseline (p = 0.03). Secretion...

  4. 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...

  5. An open label study on the supplementation of Gymnema sylvestre in type 2 diabetics.

    Science.gov (United States)

    Kumar, Smriti Nanda; Mani, Uliyar Vitaldas; Mani, Indirani

    2010-09-01

    Diabetes mellitus is a complex metabolic disorder characterized by chronic hyperglycemia, and associated with long-term damage and dysfunction of various organs. Management of diabetes is therefore vital and involves maintaining euglycemia as much as possible by reducing blood glucose and by increasing insulin sensitivity and peripheral glucose uptake. Ayurveda has promoted the management of diabetes by regulating carbohydrate metabolism using several medicinal herbs, one of which is Gymnema sylvestre (GS). GS has been used in parts of India as a hypoglycemic agent and the results have been encouraging. Accordingly, we planned a quasi-experimental study to investigate the efficacy of the herb among type 2 diabetics. Patients enrolled from free-living population were purposively assigned to experimental or control groups, based on their willingness to participate in the study. The experimental group was supplemented with 500 mg of the herb per day for a period of 3 months, and the efficacy of the herb was assessed through a battery of clinical and biochemical tests. Supplementation of the diet with GS reduced polyphagia, fatigue, blood glucose (fasting and post-prandial), and glycated hemoglobin and there was a favorable shift in lipid profiles and in other clinico-biochemical tests. These findings suggest a beneficial effect of GS in the management of diabetes mellitus.

  6. 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.

  7. A Randomized Open Label Comparison of the Effects ofRisperidone and Haloperidol on Sexual Function

    Directory of Open Access Journals (Sweden)

    S. Jaber Mousavi

    2009-12-01

    Full Text Available "n Objective: "nSexual dysfunction in patients who take antipsychotics causes adecline in their quality of life and medication acceptance. Considering the restrictions in cross sectional design of many earlier researches, we used a clinical trial aimed at assessing sexual dysfunction by substituting Risperidone, an atypical antipsychotic drug, with Haloperidol, a typical one . "n "n "nMethod: This clinical trial was conducted on 51 patients who had been using Risperidone with a minimum dose of 2 mg/daily for at least 2 months. The patients were randomly divided into 2 groups. The first group continued taking Risperidone, whereas the second group was given Haloperidol. Sexual function prior to and after the drug substitution was assessed using a sexual questionnaire designed to assess four stages of sexual function . "nResults: Compared to those who changed their medication to Haloperidol, the patients who remained on Risperidone therapy suffered from more sexual dysfunction, especially in their tendency towards having sexual activities (P= 0.01, post menstrual sexual activity (P= 0.002, and reaching orgasm in their sexual activities (P= 0.04; however in the Haloperidol group, no significant difference was observed before and after the change in medication . "nConclusion: Although Risperidone and Haloperidol can both disturb patients'sexual function, the side effects of Risperidone are stronger. Hence toprevent the decline of medication acceptance or irregular consumption by patients which may lead to possible relapse, substitution of Risperidone withanother drug with fewer side effects on sexual activities is definitely to the advantage of the patients .

  8. Piroxicam immediate release formulations: A fasting randomized open-label crossover bioequivalence study in healthy volunteers.

    Science.gov (United States)

    Helmy, Sally A; El-Bedaiwy, Heba M

    2014-11-01

    Piroxicam is a NSAID with analgesic and antipyretic properties, used for the treatment of rheumatoid diseases. The aim of this study was to evaluate the bioequivalence of two brands of piroxicam capsules (20 mg) in 24 Egyptian volunteers. The in vivo study was established according to a single-center, randomized, single-dose, laboratory-blinded, 2-period, 2-sequence, crossover study with a washout period of 3 weeks. Under fasting conditions, 24 healthy male volunteers were randomly selected to receive a single oral dose of one capsule (20 mg) of either test or reference product. Plasma samples were obtained over a 144-hour interval and analyzed for piroxicam by HPLC with UV detection. The pharmacokinetic parameters Cmax , tmax , AUC0-t , AUC0-∞ , Vd /F, Cl/F, and t1/2 were determined from plasma concentration-time profiles. The 90% confidence intervals for the ratio of log transformed values of Cmax , AUC0-t , and AUC0-∞ of the two treatments were within the acceptable range (0.8-1.25) for bioequivalence. From PK perspectives, the two piroxicam formulations were considered bioequivalent, based on the rate and extent of absorption. No adverse events occurred or were reported after a single 20-mg piroxicam and both formulations were well-tolerated.

  9. Therapeutic efficacy and safety of propylthiouracil in psoriasis: An open-label study

    Directory of Open Access Journals (Sweden)

    Pushpa Gnanaraj

    2011-01-01

    Full Text Available Background: Psoriasis is a common hyperproliferative disorder of the skin associated with significant morbidity. Most of the drugs used in psoriasis provide only a temporary relief, whereas they are riddled with potential toxicities and cost concerns. Hence, there is a constant need to explore newer, effective, orally administered, and cost-effective drugs with minimal adverse effects. In this scenario, propylthiouracil (PTU, an antithyroid thioureylene has been shown to be effective in psoriasis which satisfies the above criteria. Aim: The objective of our study is to assess the clinical efficacy of PTU in psoriasis. Methods: A total of 25 patients with plaque psoriasis were treated with oral PTU for 12 weeks. Clinical response was assessed using the "Psoriasis Area and Severity Index" (PASI score. Routine blood analyses and thyroid function tests were carried out periodically during the study. Results: Oral PTU produced significant clearing of lesions at 6 weeks and 12 weeks of the study period in all patients, as demonstrated by the reduction in PASI scores (33.9% in 6 weeks and 74.1% reduction in 12 weeks. Four patients experienced near complete clearing of the lesions. One patient developed mild elevation of liver enzymes which reversed on withdrawal of PTU. None of the patients had hypothyroidism or cytopenias. Conclusion: PTU significantly clears the lesions in psoriasis with minimal adverse effects. Hence, it can be considered as a therapeutic option in psoriasis, especially when the standard drugs cannot be used due to their toxicities or forbidding cost.

  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. Agomelatine as monotherapy for major depression: an outpatient, open-label study [Corrigendum

    Directory of Open Access Journals (Sweden)

    Pecenak J

    2013-11-01

    Full Text Available Pecenak J, Novotny V. Neuropsychiatric Disease and Treatment 2013;9:1595–1604.On page 1601, line 1 in the right-hand column, note that the drug "venlafaxine" is incorrect and should instead be "fluoxetine". The correct sentence is "The response rate in the current study was much higher than in the 6-week and 8-week double-blind, placebo-controlled studies of agomelatine13,36 and higher than in an observational study of different antidepressants where a 38.2% early remission rate and a 20.5% early response rate were found at week 6 of treatment,41 but similar to a double-blind study comparing agomelatine with fluoxetine in patients with severe depression."42Read the original article

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

    DEFF Research Database (Denmark)

    Aberer, W; Maurer, M; Reshef, A

    2014-01-01

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

  13. 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.

  14. 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

  15. 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

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

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    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.

  17. 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

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

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    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.

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

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    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.

  20. Alemtuzumab in lung transplantation: an open-label, randomized, prospective single center study.

    Science.gov (United States)

    Jaksch, P; Ankersmit, J; Scheed, A; Kocher, A; Muraközy, G; Klepetko, W; Lang, G

    2014-08-01

    Induction therapy with alemtuzumab followed by lower maintenance immunosuppression (IS) has been associated with reduced morbidity and mortality in abdominal and heart transplantation (TX). In the current study, alemtuzumab, in combination with reduced levels of maintenance IS, was compared to thymoglobulin in combination with standard IS. Sixty consecutive patients who underwent lung transplantation (LUTX) at a single center were prospectively randomized in two groups: group A received alemtuzumab in conjunction with reduced doses of tacrolimus, steroids and mycophenolate mofetil. Group B received thymoglobulin in association with standard dose IS. Patient and graft survival, freedom from acute cellular rejection (ACR), lymphocytic bronchiolitis, bronchiolitis obliterans syndrome, kidney function, infectious complications and posttransplant lymphoproliferative disorder were analyzed. Alemtuzumab induction therapy resulted in complete the absence of ACR episodes ≥ A2 within the first year post-TX. The difference to thymoglobulin was significant (alemtuzumab 0 vs. ATG 0.33; p = 0.019). All other factors studied did not show any differences between the two groups. Alemtuzumab induction therapy after LUTX in combination with reduced maintenance IS significantly reduces higher-grade rejection rates. This novel therapeutic agent had no impact on survival, infections rates, kidney function and incidence of malignancies.

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

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    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.

  2. Oral Human Immunoglobulin for Children with Autism and Gastrointestinal Dysfunction: A Prospective, Open-Label Study

    Science.gov (United States)

    Schneider, Cindy K.; Melmed, Raun D.; Barstow, Leon E.; Enriquez, F. Javier; Ranger-Moore, James; Ostrem, James A.

    2006-01-01

    Immunoglobulin secretion onto mucosal surfaces is a major component of the mucosal immune system. We hypothesized that chronic gastrointestinal (GI) disturbances associated with autistic disorder (AD) may be due to an underlying deficiency in mucosal immunity, and that orally administered immunoglobulin would be effective in alleviating chronic GI…

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

    Science.gov (United States)

    Ucler, Serap; Coskun, Ozlem; Inan, Levent E; Kanatli, Yonca

    2006-12-01

    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.

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

    OpenAIRE

    2006-01-01

    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 c...

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

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    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

  7. Evaluation of abatacept administered subcutaneously in adults with active rheumatoid arthritis: impact of withdrawal and reintroduction on immunogenicity, efficacy and safety (phase Iiib ALLOW study)

    Science.gov (United States)

    Kaine, Jeffrey; Gladstein, Geoffrey; Strusberg, Ingrid; Robles, Manuel; Louw, Ingrid; Gujrathi, Sheila; Pappu, Ramesh; Delaet, Ingrid; Pans, Miranda; Ludivico, Charles

    2012-01-01

    Objectives To assess the effect of a temporary interruption in subcutaneous (SC) abatacept on immunogenicity, safety and efficacy in patients with active rheumatoid arthritis despite methotrexate in a phase III trial. Methods Following a 12-week open-label introduction (period I; intravenous abatacept loading dose and weekly fixed-dose SC abatacept 125 mg), patients were randomised 2:1 to double-blind SC placebo or SC abatacept for 12 weeks (period II). At the end of period II, patients receiving SC abatacept continued treatment and patients on placebo were reintroduced to SC abatacept (12-week open-label period III). The co-primary end points were ELISA-detected immunogenicity rate and safety at the end of period II. Efficacy was also monitored. Results Of 167 patients entering period I, 72% qualified for period II; during periods II and III, three patients discontinued treatment. Mean (SD) disease duration was 6.6 (6.5) years and Disease Activity Score 28 was 4.8 (0.8). The primary end point was met, with a non-significant increase in immunogenicity upon withdrawal (7/73 placebo vs 0/38 abatacept in period II; p=0.119) which was reversed upon reintroduction of SC abatacept (2/73 vs 1/38, end period III). Safety was comparable regardless of withdrawal, with no unexpected events upon reintroduction. Two patients experienced reactions at the SC injection site. On withdrawal, patients experienced slight worsening in efficacy which improved following reintroduction. Conclusions Overall immunogenicity to SC abatacept is low, consistent with intravenous abatacept, and is not significantly affected by a 3-month interruption and reintroduction. This stop–start schedule was well tolerated, with little impact on safety and efficacy. These are important considerations for the clinical use of SC abatacept. ClinicalTrials gov Identifier NCT00533897 PMID:21917824

  8. New treatment possibilities for rheumatoid arthritis: the Russian experience in using certolizumab pegol

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    Dmitry Evgenyevich Karateev

    2012-01-01

    Full Text Available Certolizumab pegol (CZP is a new drug from the group of tumor necrosis factor a inhibitors. The efficacy and safety CZP in the treatment of rheumatoid arthritis (RA have been studied in the international 52-week RAPID-1 and 24-week RAPID-2 clinical trials that studied the use of CZP in combination with methotrexate (MTX in patients with active RA unresponsive to MTX. The study populations of the RAPID 1 and RAPID 2 trials constituted the major portion of Russian patients (11.8 and 18.4%, respectively, including that in the prolonged open-labeled phases. The results of using CZP in Russian patients in the RAPID trials showed that they displayed a highly stable response to treatment and a rapidly developing clinical effect, that a therapy response could be predicted in the first 12 weeks, and that the incidence of local postinjection reactions was low.

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

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    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

  10. Evaluation of a prototype dengue-1 DNA vaccine in a Phase 1 clinical trial.

    Science.gov (United States)

    Beckett, Charmagne G; Tjaden, Jeffrey; Burgess, Timothy; Danko, Janine R; Tamminga, Cindy; Simmons, Monika; Wu, Shuenn-Jue; Sun, Peifang; Kochel, Tadeusz; Raviprakash, Kanakatte; Hayes, Curtis G; Porter, Kevin R

    2011-01-29

    Candidate dengue DNA vaccine constructs for each dengue serotype were developed by incorporating pre-membrane and envelope genes into a plasmid vector. A Phase 1 clinical trial was performed using the dengue virus serotype-1 (DENV-1) vaccine construct (D1ME(100)). The study was an open-label, dose-escalation, safety and immunogenicity trial involving 22 healthy flavivirus-naïve adults assigned to one of two groups. Each group received three intramuscular injections (0, 1, and 5 months) of either a high dose (5.0mg, n=12) or a low dose (1.0mg, n=10) DNA vaccine using the needle-free Biojector(®) 2000. The most commonly reported solicited signs and symptoms were local mild pain or tenderness (10/22, 45%), local mild swelling (6/22, 27%), muscle pain (6/22, 27%) and fatigue (6/22, 27%). Five subjects (41.6%) in the high dose group and none in the low dose group developed detectable anti-dengue neutralizing antibodies. T-cell IFN gamma responses were detected in 50% (4/8) and 83.3% (10/12) of subjects in the low and high dose groups, respectively. The safety profile of the DENV-1 DNA vaccine is acceptable at both doses administered in the study. These results demonstrate a favorable reactogenicity and safety profile of the first in human evaluation of a DENV-1 DNA vaccine.

  11. Effect of Food Intake on the Pharmacodynamics of Tenapanor: A Phase 1 Study.

    Science.gov (United States)

    Johansson, Susanne A; Knutsson, Mikael; Leonsson-Zachrisson, Maria; Rosenbaum, David P

    2017-03-24

    Tenapanor (RDX5791/AZD1722) is a minimally systemic small-molecule inhibitor of the sodium/hydrogen exchanger NHE3. Tenapanor acts in the gut to reduce absorption of sodium and phosphate. This phase 1 open-label, 3-way crossover study (NCT02226783) evaluated the effect of food on the pharmacodynamics of tenapanor. Eighteen volunteers completed a randomized sequence of three 4-day treatments with tenapanor hydrochloride 15 mg twice daily: before food, after food, and while fasting. Participants received a diet standardized for sodium content. Stool sodium was significantly higher with tenapanor administration before versus after food (difference, +8.8 mmol/day, P = .006) or while fasting (+11.8 mmol/day, P = .0004). Differences in urinary sodium were not significant. Stool phosphorus was not significantly different with tenapanor before versus after food and significantly higher before food versus while fasting (+4.9 mmol/day, P = .006). Urinary phosphorus was significantly lower when tenapanor was administered before (-3.9 mmol/day, P = .0005) or after food (-3.7 mmol/day, P = .0009) versus while fasting. No serious adverse events were reported. These data suggest the effect of tenapanor on sodium absorption is most pronounced when administered before meals, whereas the effect on phosphate is similar whether administered before or after meals. This may support different timings of tenapanor administration with respect to food for sodium- and phosphate-related indications.

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

    Science.gov (United States)

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

    2014-07-03

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

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Recombinant human interleukin-1 receptor antagonist in severe traumatic brain injury: a phase II randomized control trial.

    Science.gov (United States)

    Helmy, Adel; Guilfoyle, Mathew R; Carpenter, Keri L H; Pickard, John D; Menon, David K; Hutchinson, Peter J

    2014-05-01

    Traumatic brain injury (TBI) is the commonest cause of death and disability in those aged under 40 years. Interleukin-1 receptor antagonist (IL1ra) is an endogenous competitive antagonist at the interleukin-1 type-1 receptor (IL-1R). Antagonism at the IL-1R confers neuroprotection in several rodent models of neuronal injury (i.e., trauma, stroke and excitotoxicity). We describe a single center, phase II, open label, randomized-control study of recombinant human IL1ra (rhIL1ra, anakinra) in severe TBI, at a dose of 100 mg subcutaneously once a day for 5 days in 20 patients randomized 1:1. We provide safety data (primary outcome) in this pathology, utilize cerebral microdialysis to directly determine brain extracellular concentrations of IL1ra and 41 cytokines and chemokines, and use principal component analysis (PCA) to explore the resultant cerebral cytokine profile. Interleukin-1 receptor antagonist was safe, penetrated into plasma and the brain extracellular fluid. The PCA showed a separation in cytokine profiles after IL1ra administration. A candidate cytokine from this analysis, macrophage-derived chemoattractant, was significantly lower in the rhIL1ra-treated group. Our results provide promising data for rhIL1ra as a therapeutic candidate by showing safety, brain penetration and a modification of the neuroinflammatory response to TBI by a putative neuroprotective agent in humans for the first time.

  20. Early treatment with intravenous metoprolol for suspected acute myocardial infarction: a phase IV United States trial. Phase IV Metoprolol in Myocardial Infarction Study Group.

    Science.gov (United States)

    Antman, E M; Dupont, W D; Bonalsky, J; Califf, R M; Corwin, S; Fink, L; Hansen, D E; Kawanishi, D T; Kronenberg, M W; McKay, C R

    1989-05-01

    Recent randomized clinical trials have shown that total mortality and cardiovascular mortality are reduced by the early intravenous administration of beta-blockers to patients suspected of suffering from acute myocardial infarction. These trials were conducted on patients meeting strict entry criteria. In order to assess this therapy when applied to a broader range of myocardial infarction patients, we performed a Phase IV study of metoprolol in acute myocardial infarction. The study was designed to test whether early (less than 8 hours from onset of chest pain) intervention by practicing physicians with open label intravenous metoprolol for cases of suspected acute myocardial infarction achieved mortality results similar to those obtained in large randomized clinical trials. We studied 3824 patients treated by 741 physicians representing a broad spectrum of clinical practice in the United States. Seventy-two percent of the patients entered into the study had confirmed myocardial infarction (39% anterior, 39% inferior, 22% other locations) and 85% of all individuals treated tolerated the full intravenous dose of 15 mg of metoprolol. The 15 day total mortality and cardiovascular mortality rates were 4.9% and 4.5%; 90 day mortality rates were 6.9 and 5.9%. Patients with anterior infarctions had a significantly greater cumulative mortality rate than patients with other types of infarctions. Marked bradycardia (heart rate less than 45 beats per minute) in the first 8 hours post treatment occurred in 4.7% cases and hypotension (systolic blood pressure less than 90 mm Hg) occurred in 9.8% of cases. When compared with the results of the Göteborg and MIAMI trials of metoprolol, it appears that there is no appreciable increase in mortality or morbidity when metoprolol is used in the community practice of acute coronary care.

  1. Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOSan open-label, international, randomised controlled trial-1): an open-label, international, randomised controlled trial

    DEFF Research Database (Denmark)

    Marina, Neyssa M; Smeland, Sigbjørn; Bielack, Stefan S

    2016-01-01

    . New strategies are required to improve outcomes in this setting. FUNDING: UK Medical Research Council, National Cancer Institute, European Science Foundation, St Anna Kinderkrebsforschung, Fonds National de la Recherche Scientifique, Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, Parents...... Organization, Danish Medical Research Council, Academy of Finland, Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, Federal Ministry of Education and Research, Semmelweis Foundation, ZonMw (Council for Medical Research), Research Council of Norway, Scandinavian Sarcoma Group, Swiss Paediatric Oncology...

  2. 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)

    van Beek, M.H.C.T.; Oude Voshaar, R.C.; Beek, A.M.; van Zijderveld, G.A.; Visser, S.; Speckens, A.E.M.; Batelaan, N.; van Balkom, A.J.L.M.

    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

  3. Efficacy and safety of telaprevir (TVR) triple therapy in a 'real-life' cohort of 102 patients with HCV genotype 1: interim analysis after 24 weeks of treatment.

    Science.gov (United States)

    Werner, C R; Franz, C; Egetemeyr, D P; Janke-Maier, P; Malek, N P; Lauer, U M; Berg, C P

    2014-05-01

    Since 2011, telaprevir (TVR)-based triple therapy is the new treatment standard for hepatitis C genotype 1 virus infection. The aim of our retrospective interim analysis encompassing the first 24 weeks on TVR-based triple therapy was to assess 'real-life' antiviral efficacy and side effects in a large single-centre cohort, both in comparison with the data obtained in large prospective clinical trials. In total, we treated 102 patients: 24 treatment-naïve patients, 58 patients pretreated with PEG-IFN/RBV (thereof: 28 with nonresponse, 25 with relapse, five unknown) and 20 patients who previously had received nonpegylated interferon. 74 of 102 patients were assigned with HCV genotype 1b; 34 of 102 patients were treated in the context of liver cirrhosis. 72 of 102 patients have reached treatment week 24 (mean treatment duration 31 weeks). In the ITT analysis, overall response rates were at: week 4: 66%; week 12: 85%; and week 24: 78%. So far, 24 patients discontinued treatment prematurely, of those, 10 patients were due to virological failure. Haematological side effects were frequent (40% anaemia), as were 'flu-like' symptoms (94%), rash (65%) and pruritus (79%). According to our interim ITT analysis encompassing up to 24 weeks of TVR-based triple therapy, our 'real-life' antiviral effects are comparable to the results of large multicentric clinical trials. However, TVR-based triple therapy exhibited a high frequency of side effects requiring multiple therapeutic interventions. Notably, in our 'real-life' cohort, no lethal case was observed so far.

  4. 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

    A recent nonrandomized pilot trial showed that hepatitis C virus (HCV) patients with genotype 2/3 and rapid virological response (RVR) had a 90% sustained virological response (SVR) rate after 14 weeks of treatment. We aimed to assess this concept in a randomized controlled trial. In the trial, 428...

  5. 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.

  6. A randomised, open-label, crossover study of the dopamine agonist, pramipexole, in patients with sleep bruxism.

    Science.gov (United States)

    Cahlin, Birgitta Johansson; Hedner, Jan; Dahlström, Lars

    2017-02-01

    Sleep bruxism bears several similarities to restless legs syndrome, and a link to changes in central dopamine activity has been considered in both conditions. The dopamine agonist pramipexole is currently indicated for the symptomatic treatment of restless legs. The effect of pramipexole on sleep bruxism was investigated in subjects with 'probable bruxism' recruited at the Orofacial Pain Clinic. Thirteen patients underwent polysomnographic recordings, including bilateral masseter electromyographic activity. Following habituation to the recording equipment, a baseline registration was used to confirm bruxism [total episodes per hour, mean 11.3 (6.3)]. Following randomisation, subjects received no treatment or pramipexole titrated from 0.09 to 0.54 mg, o.d., for 3 weeks according to a crossover procedure. A polysomnographic-electromyographic registration was performed at the end of each period. Pramipexole was associated with more frequent awakenings and a reduction in rapid eye movement sleep (both P ≤ 0.02). Sleep apnea decreased marginally after pramipexole (apnea-hypopnea index 17.1 compared with control 21.5, P ≤ 0.05). The number of bruxism episodes, phasic, tonic and mixed per hour, remained unchanged after pramipexole [total episodes per hour 12.7 (8.5) and 9.8 (5.2) during pramipexole and control conditions, respectively]. It is concluded, from this pilot study, that sleep bruxism is not affected by the dopaminergic agent, pramipexole.

  7. SPINAL ANESTHESIA A BETTER AND EFFECTIVE ALTERNATIVE TO GENERAL ANEASTHESIA IN SPINE SURGERIES: A PROSPECTIVE OPEN LABEL SINGLE ARM STUDY

    Directory of Open Access Journals (Sweden)

    Kumar Babu

    2014-11-01

    Full Text Available : INTRODUCTION: In all practical purposes various thoraco lumbar and lumbar surgeries like discectomy, laminectomy and spinal fusion procedures are usually performed under general anesthesia (GA. Our aim of this study is to assess whether spinal anesthesia is a better and effective alternative to general anesthesia in terms of economic advantage and functional recovery with both intra and post-operative heamodynamic stability. METHODS: In our study hundred patients with age group 25-45 yrs within the ASA criteria of class I-III were enrolled. All patients were randomly selected based on age, sex, ASS criteria, duration of surgery, heart rate (HR, mean arterial pressure (MAP, blood loss, previous history of risk factors and co morbidities. The severity of postoperative pain based on visual analogue scale (VAS and use of analgesics post operatively, were recorded. RESULTS: There were 41 males and 59 females. The mean age of the patient was 39.28±9.27 yrs. Six patients had hypertension, 11 with diabetes. Patients with ASA Grade I and II and III were 60, 34 and 6 respectively. There were no episodes of air way compromises, 2 patients had spinal aneasthesia failures, no incidence of post dural puncture headache, 3 patients had mean blood pressure fluctuations among them, one patient had post-operative paraperesis due to hematoma treated by immediate decompression, and 13 patients had usage of propofol sedation in terms of comfort. The duration of surgery (range was 77.25±22.44 min (40-120 Severity of postoperative pain after four hours of surgery on VAS was 3.24±0.46. Twenty two patients (22% required analgesics. Two patients had post-operative vomiting. CONCLUSIONS: In our study we have considered that spinal anesthesia for advantages such as less blood loss, intra operative blood pressure and heart rate changes, postoperative pain, quick functional recovery and lower incidence of pulmonary complications. Additionally, during spinal anesthesia patient extremities and chest can be reposition as needed, to avoid nerve injury, brachial plexus palsy or pressure necrosis to either the face or chest wall and finally the most important being an economical advantage and patient and surgeons satisfaction. We showed that spinal aneasthesia is better and effective alternative to GA in providing postoperative analgesia and decreasing blood loss with both intra and post-operative hemodynamic stability without increasing adverse side effects.

  8. Trazodone for the treatment of sleep disorders in dementia: an open-label, observational and review study

    Directory of Open Access Journals (Sweden)

    Einstein Francisco Camargos

    2011-02-01

    Full Text Available Sleep disorders (SD in patients with dementia are very common in clinical practice. The use of antidepressants with hypnotic actions, such as trazodone, plays an important role in these cases. The aim of this study is to present a profile of the use of trazodone in demented patients with SD, as well as a review of trazodone hydrochloride in SD. We evaluated 178 elderly patients with Alzheimer's disease and other dementias, clinically presenting SD and treated with hypnosedative medications. In the one-year period comprising the study, 68 (38.2% of the 178 had sleep disorders. Most patients (114; 64% had a diagno