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Parallel-group Study (parallel-group + study)
Selected AbstractsA Short-Term, Randomized, Double-Blind, Parallel-Group Study to Evaluate the Efficacy and Safety of Dronedarone versus Amiodarone in Patients with Persistent Atrial Fibrillation: The DIONYSOS StudyJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2010JEAN-YVES LE HEUZEY M.D. Dronedarone versus Amiodarone in Patients with AF.,,Introduction: We compared the efficacy and safety of amiodarone and dronedarone in patients with persistent atrial fibrillation (AF). Methods: Five hundred and four amiodarone-naïve patients were randomized to receive dronedarone 400 mg bid (n = 249) or amiodarone 600 mg qd for 28 days then 200 mg qd (n = 255) for at least 6 months. Primary composite endpoint was recurrence of AF (including unsuccessful electrical cardioversion, no spontaneous conversion and no electrical cardioversion) or premature study discontinuation. Main safety endpoint (MSE) was occurrence of thyroid-, hepatic-, pulmonary-, neurologic-, skin-, eye-, or gastrointestinal-specific events, or premature study drug discontinuation following an adverse event. Results: Median treatment duration was 7 months. The primary composite endpoint was 75.1 and 58.8% with dronedarone and amiodarone, respectively, at 12 months (hazard ratio [HR] 1.59; 95% confidence interval [CI] 1.28,1.98; P < 0.0001), mainly driven by AF recurrence with dronedarone compared with amiodarone (63.5 vs 42.0%). AF recurrence after successful cardioversion was 36.5 and 24.3% with dronedarone and amiodarone, respectively. Premature drug discontinuation tended to be less frequent with dronedarone (10.4 vs 13.3%). MSE was 39.3 and 44.5% with dronedarone and amiodarone, respectively, at 12 months (HR = 0.80; 95% CI 0.60,1.07; P = 0.129), and mainly driven by fewer thyroid, neurologic, skin, and ocular events in the dronedarone group. Conclusion: In this short-term study, dronedarone was less effective than amiodarone in decreasing AF recurrence, but had a better safety profile, specifically with regard to thyroid and neurologic events and a lack of interaction with oral anticoagulants. (J Cardiovasc Electrophysiol, Vol. 21, pp. 597-605, June 2010) [source] Treatment of Premature Ejaculation in the Asia-Pacific Region: Results from a Phase III Double-blind, Parallel-group Study of DapoxetineTHE JOURNAL OF SEXUAL MEDICINE, Issue 1pt1 2010Chris McMahon MBBS, FAChSHM ABSTRACT Introduction., Dapoxetine is a short-acting selective serotonin reuptake inhibitor that was recently approved for the on-demand treatment of premature ejaculation (PE). Aim., To evaluate the efficacy and safety of dapoxetine 30 mg and 60 mg on demand (prn) in men with PE from the Asia-Pacific region. Methods., This randomized, double-blind, parallel-group, placebo-controlled trial enrolled men who were 18 years or older; in a monogamous, heterosexual relationship for at least 6 months; met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision, criteria for PE for at least 6 months; and had an intravaginal ejaculatory latency time (IELT) of 2 minutes or less in at least 75% of sexual intercourse episodes. Subjects received placebo, dapoxetine 30 mg, or dapoxetine 60 mg prn (1,3 hours before intercourse) for 12 weeks. Main Outcome Measures., Stopwatch-measured Average IELT, the Premature Ejaculation Profile (PEP), Clinical Global Impression (CGI) of change in PE, treatment-emergent adverse events (TEAEs). Results., Of the 1,067 subjects randomized, 858 completed the study. Mean Average IELT increased from approximately 1.1 minutes at baseline (across groups) to 2.4, 3.9, and 4.2 minutes with placebo, dapoxetine 30 mg, and dapoxetine 60 mg, respectively, and geometric mean Average IELT increased from approximately 0.9 minutes at baseline (across groups) to 1.8, 2.7, and 3.1 minutes, respectively (fold-increases of 2.0, 2.8, and 3.3, respectively). All PEP measures and the CGI of change were significantly improved with dapoxetine vs. placebo at study endpoint (P , 0.005 for all). The most common TEAEs with dapoxetine included nausea, dizziness, somnolence, headache, vomiting, diarrhea, and nasopharyngitis; TEAEs led to discontinuation in 0.3%, 1.7%, and 5.1% of subjects with placebo, dapoxetine 30 mg, and dapoxetine 60 mg, respectively. Conclusions., Dapoxetine treatment significantly prolonged IELT and improved PEP measures and was generally well tolerated in men with PE in the Asia-Pacific region. McMahon C, Kim SW, Park NC, Chang C, Rivas D, Tesfaye F, Rothman M, and Aquilina J on behalf of the dapoxetine 3003 study investigators. Treatment of premature ejaculation in the Asia-Pacific region: Results from a phase III double-blind, parallel-group study of dapoxetine. J Sex Med 2010;7:256,268. [source] Safety of sertindole versus risperidone in schizophrenia: principal results of the sertindole cohort prospective study (SCoP)ACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2010S. H. L. Thomas Thomas SHL, Drici MD, Hall GC, Crocq MA, Everitt B, Lader MH, Le Jeunne C, Naber D, Priori S, Sturkenboom M, Thibaut F, Peuskens J, Mittoux A, Tanghøj P, Toumi M, Moore ND, Mann RD. Safety of sertindole versus risperidone in schizophrenia: principal results of the sertindole cohort prospective study (SCoP) Objective:, To explore whether sertindole increases all-cause mortality or cardiac events requiring hospitalization, compared with risperidone. Method:, Multinational randomized, open-label, parallel-group study, with blinded classification of outcomes, in 9858 patients with schizophrenia. Results:, After 14147 person-years, there was no effect of treatment on overall mortality (sertindole 64, risperidone 61 deaths, Hazard Ratio (HR) = 1.12 (90% CI: 0.83, 1.50)) or cardiac events requiring hospitalization [sertindole 10, risperidone 6, HR = 1.73 (95% CI: 0.63, 4.78)]: Of these, four were considered arrhythmia-related (three sertindole, one risperidone). Cardiac mortality was higher with sertindole (Independent Safety Committee (ISC): 31 vs. 12, HR=2.84 (95% CI: 1.45, 5.55), P = 0.0022; Investigators 17 vs. 8, HR=2.13 (95% CI: 0.91, 4.98), P = 0.081). There was no significant difference in completed suicide, but fewer sertindole recipients attempted suicide (ISC: 68 vs. 78, HR=0.93 (95% CI: 0.66, 1.29), P = 0.65; Investigators: 43 vs. 65, HR=0.67 (95% CI: 0.45, 0.99), P = 0.044). Conclusion:, Sertindole did not increase all-cause mortality, but cardiac mortality was higher and suicide attempts may be lower with sertindole. [source] Earlier triple therapy with pioglitazone in patients with type 2 diabetesDIABETES OBESITY & METABOLISM, Issue 9 2009G. Charpentier Aims: This study assessed the efficacy of add-on pioglitazone vs. placebo in patients with type 2 diabetes uncontrolled by metformin and a sulphonylurea or a glinide. Methods: This multicentre, double-blind, parallel-group study randomized 299 patients with type 2 diabetes to receive 30 mg/day pioglitazone or placebo for 3 months. After this time, patients continued with pioglitazone, either 30 mg [if glycated haemoglobin A1c (HbA1c) ,6.5%] or titrated up to 45 mg (if HbA1c >6.5%), or placebo for a further 4 months. The primary efficacy end-point was improvement in HbA1c (per cent change). Secondary end-points included changes in fasting plasma glucose (FPG), insulin, C-peptide, proinsulin and lipids. The proinsulin/insulin ratio and homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of ,-cell function (HOMA-B) were calculated. Results: Pioglitazone add-on therapy to failing metformin and sulphonylurea or glinide combination therapy showed statistically more significant glycaemic control than placebo addition. The between-group difference after 7 months of triple therapy was 1.18% in HbA1c and ,2.56 mmol/l for FPG (p < 0.001). Almost half (44.4%) of the patients in the pioglitazone group who had a baseline HbA1c level of <8.5% achieved the HbA1c target of < 7.0% by final visit compared with 4.9% in the placebo group. When the baseline HbA1c level was , 8.5%, 13% achieved the HbA1c target of < 7.0% in the pioglitazone group and none in the placebo group. HOMA-IR, insulin, proinsulin and C-peptide decreased and HOMA-B increased in the pioglitazone group relative to the placebo group. Conclusions: In patients who were not well controlled with dual combination therapy, the early addition of pioglitazone improved HbA1c, FPG and surrogate measures of ,-cell function. Patients were more likely to reach target HbA1c levels (< 7.0%) with pioglitazone treatment if their baseline HbA1c levels were < 8.5%, highlighting the importance of early triple therapy. [source] Rosiglitazone RECORD study: glucose control outcomes at 18 monthsDIABETIC MEDICINE, Issue 6 2007P. D. Home Abstract Aims To compare glucose control over 18 months between rosiglitazone oral combination therapy and combination metformin and sulphonylurea in people with Type 2 diabetes. Methods RECORD, a multicentre, parallel-group study of cardiovascular outcomes, enrolled people with an HbA1c of 7.1,9.0% on maximum doses of metformin or sulphonylurea. If on metformin they were randomized to add-on rosiglitazone or sulphonylurea (open label) and if on sulphonylurea to rosiglitazone or metformin. HbA1c was managed to , 7.0% by dose titration. A prospectively defined analysis of glycaemic control on the first 1122 participants is reported here, with a primary outcome assessed against a non-inferiority margin for HbA1c of 0.4%. Results At 18 months, HbA1c reduction on background metformin was similar with rosiglitazone and sulphonylurea [difference 0.07 (95% CI ,0.09, 0.23)%], as was the change when rosiglitazone or metformin was added to sulphonylurea [0.06 (,0.09, 0.20)%]. At 6 months, the effect on HbA1c was greater with add-on sulphonylurea, but was similar whether sulphonylurea was added to rosiglitazone or metformin. Differences in fasting plasma glucose were not statistically significant at 18 months [rosiglitazone vs. sulphonylurea ,0.36 (,0.74, 0.02) mmol/l, rosiglitazone vs. metformin ,0.34 (,0.73, 0.05) mmol/l]. Increased homeostasis model assessment insulin sensitivity and reduced C-reactive protein were greater with rosiglitazone than metformin or sulphonylurea (all P , 0.001). Body weight was significantly increased with rosiglitazone compared with sulphonylurea [difference 1.2 (0.4, 2.0) kg, P = 0.003] and metformin [difference 4.3 (3.6, 5.1) kg, P < 0.001]. Conclusions In people with diabetes, rosiglitazone in combination with metformin or sulphonylurea was demonstrated to be non-inferior to the standard combination of metformin + sulphonylurea in lowering HbA1c over 18 months, and produces greater improvements in C-reactive protein and basal insulin sensitivity but is also associated with greater weight gain. [source] Sumatriptan Nasal Spray in Adolescent Migraineurs: A Randomized, Double-Blind, Placebo-Controlled, Acute StudyHEADACHE, Issue 2 2006Paul Winner DO Objective.,To compare the efficacy and tolerability of sumatriptan nasal spray (NS) (5, 20 mg) versus placebo in the acute treatment of migraine in adolescent subjects. Background.,Currently, no triptan is approved in the United States for the treatment of migraine in adolescent subjects (12 to 17 years). In a previous randomized, placebo-controlled study of 510 adolescent subjects, sumatriptan NS at 5, 10, and 20 mg doses was well tolerated. However, the primary efficacy analysis for headache relief with 20 mg at 2 hours did not demonstrate statistical significance (P= .059). A second study was initiated to evaluate the efficacy of sumatriptan NS in this population. Methods.,This was a randomized (1:1:1), placebo-controlled, double-blind, parallel-group study. Overall, 738 adolescent subjects (mean age: 14 years) with ,6-month history of migraine (with or without aura) self-treated a single attack of moderate or severe migraine. The primary endpoints were headache relief at 1 hour and sustained relief from 1 to 24 hours. Pain-free rates, presence/absence of associated symptoms, headache recurrence, and use of rescue medications were also assessed. Tolerability was based on adverse events (AEs) and vital signs. Results.,Sumatriptan NS 20 mg provided greater headache relief than placebo at 30 minutes (42% vs. 33%, respectively; P= .046) and 2 hours (68% vs. 58%; P= .025) postdose, but did not reach statistical significance at 1 hour (61% vs. 52%; P= .087) or for sustained headache relief from 1 to 24 hours (P= .061). Significant differences (P < .05) in favor of sumatriptan NS 20 mg over placebo were observed for several secondary efficacy endpoints including sustained relief from 2 to 24 hours. In general, sumatriptan NS 5 mg percentages were slightly higher than placebo but the differences did not reach statistical significance. Both doses of sumatriptan NS were well tolerated. No AEs were serious or led to study withdrawal. The most common event was taste disturbance (2%, placebo; 19%, sumatriptan NS 5 mg; 25%, sumatriptan NS 20 mg). Conclusions.,This study suggests that sumatriptan may be beneficial to some adolescents and is generally well tolerated in the acute treatment of migraine in this population. [source] Pilot trial: Pioglitazone versus placebo in patients with plaque psoriasis (the P6)INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 4 2005Nusrat Shafiq MD Background, Disordered differentiation and hyperproliferation of keratinocytes with inflammation are the hallmarks of psoriasis. Ligand activation of peroxisome proliferator receptor-, (a class of nuclear receptors) by thiazolidinediones can normalize the histologic features of psoriasis. Method, In a 10-week, double-blind, randomized, placebo-controlled, parallel-group study, 70 patients with moderate to severe psoriasis received one of the following treatments: pioglitazone 15 mg, pioglitazone 30 mg or placebo. Efficacy was evaluated by observing the change in the psoriasis area and severity index (PASI) after 10 weeks of treatment. Results, There was a dose-dependent improvement in psoriasis. Median PASI scores at the end of 10 weeks were significantly reduced in the pioglitazone treatment groups as compared to the placebo-treated group. The psoriasis lesions cleared in more than 40% of patients treated with pioglitazone as compared to 12.5% of those with placebo. The percentage reduction in mean PASI scores was 21.6%, 41.1% and 47.5% in the placebo, pioglitazone 15 mg, and 30 mg groups, respectively. No serious adverse events were detected. Conclusion, This is the first report from a controlled trial demonstrating that pioglitazone could be considered as an efficacious and safe agent for the treatment of plaque psoriasis. The optimum dose and duration of pioglitazone therapy remain to be determined. [source] Efficacy and safety of dutasteride in Japanese men with benign prostatic hyperplasiaINTERNATIONAL JOURNAL OF UROLOGY, Issue 9 2009Taiji Tsukamoto Objectives: To assess the efficacy and safety of dutasteride in Japanese men with benign prostatic hyperplasia (BPH). Methods: This was a randomized, double-blind, placebo-controlled, parallel-group study. A total of 378 subjects with clinical BPH having an International Prostate Symptom Score (IPSS) of 8 points or greater, a prostate volume of 30 mL or greater, and a maximal urinary flow rate (Qmax) of 15 mL/s or less were randomized to receive placebo or dutasteride once daily for 52 weeks. Subjects were stratified according to tamsulosin use at baseline. The numbers of subjects with and without tamsulosin use were 242 and 136, respectively. IPSS, Qmax, prostate volume and drug safety were evaluated. Results: Continued improvement in IPSS was noted in the dutasteride group, and dutasteride significantly decreased IPSS compared with placebo. At week 52, dutasteride significantly improved Qmax and prostate volume compared with placebo. Drug-related sexual function events in the dutasteride group were infrequent and generally were not treatment limiting. Conclusions: Dutasteride improves urinary symptoms and flow rate and reduces prostate volume. In Japanese men with BPH, it is effective and generally well tolerated during the one-year treatment period. [source] Placebo-controlled, double-blind dose-finding study of entacapone in fluctuating parkinsonian patients,MOVEMENT DISORDERS, Issue 1 2007Yoshikuni Mizuno MD Abstract We conducted a multicenter randomized, placebo-controlled double-blind parallel-group study in Japanese Parkinson's disease (PD) patients with wearing-off motor fluctuations to determine the clinical efficacy and safety of entacapone as an adjunct to concomitant treatment with levodopa and a dopa decarboxylase inhibitor (DCI). We randomized 341 patients to receive entacapone 100 or 200 mg or placebo per dose of levodopa/DCI for 8 weeks. The primary efficacy variable was on time change while awake, determined by patients' diaries. Mean baseline on time in each group was approximately 8 hours. Mean on time change at final assessment was 1.4 hours each for entacapone 100-mg and 200-mg groups and by 0.5 hours for the placebo group (P < 0.05). The two entacapone doses were equally efficacious. Adverse events occurred in 79 patients (69.9%) in placebo, 82 (72.6%) in 100 mg, and 98 (86.0%) in 200 mg. The most common adverse event with entacapone was an increase in dyskinesias. The overall safety profile was satisfactory in both entacapone groups. In conclusion, both entacapone 100 and 200 mg were equally effective in increasing on time of PD patients with wearing-off fluctuations, although the safety and tolerability profile appeared more favorable for the 100-mg dose. © 2006 Movement Disorder Society [source] CONTROLLED-RELEASE OXYCODONE RELIEVES MODERATE TO SEVERE PAIN IN A 3-MONTH STUDY OF PERSISTENT MODERATE TO SEVERE BACK PAINPAIN MEDICINE, Issue 2 2002Article first published online: 4 JUL 200 Patricia Richards, MD, PhD; Pinggao Zhang, PhD; Michael Friedman, PhD; Rahul Dhanda, PhD. (Purdue Pharma L.P.) Introduction: Opioids are frequently prescribed for management of persistent low back pain, however, efficacy has not been well documented, and concerns are that opioids may impair physical functioning. Objective: To compare controlled-release oxycodone (CRO) with placebo in controlling pain and to observe the effect of CRO on quality of life and functionality. Methods: A double-blind, randomized, placebo-controlled, parallel-group study of 3 months duration was conducted in 110 subjects (49 males, 61 females), mean age 48 years (19,80 years). Subjects had a 3- to 12-month history of moderate to severe persistent low back pain and were previously unresponsive to therapeutic doses of NSAIDs, and/or low dose combination opioid analgesics. At baseline 4% of subjects were on opioids, 39% on NSAIDs, and 57% both NSAIDs and opioids. Subjects were treated with 10 mg CRO tablet or 10 mg oral placebo q12h, titrated to stable pain control. Existing treatment regimens of acetaminophen, NSAIDs, or oral steroids were allowed to continue. The Brief Pain Inventory (BPI), the Roland Morris Functionality Questionnaire, and the MOS 36-Item Short-Form Health Survey (SF-36) were the measures of pain intensity, functionality, and quality of life. Treatments were compared using repeated measures ANCOVA with baseline value as covariate. Results: CRO treatment was significantly superior to placebo on the BPI average pain intensity and average percent pain relief scores overall (4.6 vs 5.4, P = .03, and 47.2 vs 36.3, P = .05, respectively). Fewer CRO subjects discontinued because of inadequate pain control (P < .001). No significant differences between treatments were observed in either Roland Morris or SF-36 scores. Common adverse events for CRO were nausea, constipation, somnolence, headache, and pruritus, consistent with opioid use. Conclusions: Three-month treatment with CRO provides significant pain relief for subjects with persistent moderate to severe back pain, without significantly impairing functionality and quality of life. The support of Purdue Pharma L.P. for this research project is gratefully acknowledged. [source] HPA axis safety of fluticasone furoate nasal spray once daily in children with perennial allergic rhinitisPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 3 2009Ita Tripathy The effects of intranasal corticosteroids (INSs) on the hypothalamic,pituitary,adrenal (HPA) axis should be assessed for any to be marketed INS. The objective of this study was to assess the effects of fluticasone furoate nasal spray (FFNS) on cortisol production (as a measure of HPA axis function) following 6 wk of treatment with FFNS 110 ,g once daily (QD) compared with placebo in pediatric patients with perennial allergic rhinitis (PAR). In this double-blind, parallel-group study, patients (n = 112) aged 2,11 yr with a 1-yr history of PAR (6 months for patients aged 2,3 yr) were randomized in a 1:1 ratio to either placebo or FFNS. Serum cortisol (SC) concentrations and urinary cortisol (UC) excretion were measured over a 24-h period at the randomization (baseline) and final treatment (week 6) visits for HPA axis evaluation in a domiciled environment (overnight in the clinic). Plasma samples were collected for FFNS at several time points over the 24 h after the final dose for pharmacokinetic analyses. FFNS was non-inferior to placebo with respect to change from baseline (expressed as a ratio) in 24-h SC weighted mean. The lower limit of the two-sided 95% confidence interval (CI) for the treatment ratio was greater than the pre-specified non-inferiority margin of 0.8 (treatment ratio = 0.97, 95% CI 0.88,1.07). UC excretion over 24 h at baseline and end of treatment was similar between treatment groups; no patients had 24-h excretion levels below normal range after 6 wk of treatment. Plasma concentrations of FFNS were generally non-quantifiable (<10 pg/ml). Results of the current study indicate that FFNS 110 ,g QD has no significant effect on HPA axis function in 2- to 11-yr-old pediatric patients with PAR. [source] Written action plans in chronic obstructive pulmonary disease increase appropriate treatment for acute exacerbationsRESPIROLOGY, Issue 5 2006Richard WOOD-BAKER Objective and background: COPD is a progressive disorder characterized by periodic exacerbations. While comprehensive self-management programmes decrease health-care resource utilization, the essential components are unclear. We performed a study of written action plans in the management of COPD. Methodology: A randomized, controlled, prospective parallel-group study compared written action plans to usual practice. Subjects: Recruited from general practices, received an educational intervention with or without an action plan, which usually emphasized prompt treatment with antibiotics and corticosteroids. Subjects were followed up 3-monthly for a year. Results: One hundred and thirty-nine participants, mean FEV1 45 ± 16% predicted, were recruited, 81% completing the study. Both groups had a decline in lung function and physical activity, but increase in quality of life over the study period. Exacerbations were common. The intervention group was significantly more likely to have treatment with antibiotics (,2 = 3.86; d.f. = 1; P = 0.05) or short course oral corticosteroids (,2 = 14.25; d.f. = 1; P < 0.001). No differences were found between the number of general practitioner consultations, attendances at emergency departments or hospitalizations. Conclusions: The use of a written action plan in COPD increased appropriate therapeutic interventions for exacerbations, but this effect was not associated with a decrease in the use of health-care resources. [source] Improvement in health-related quality of life with fluticasone propionate compared with budesonide or beclomethasone dipropionate in adults with severe asthmaRESPIROLOGY, Issue 3 2003Carolyn RUTHERFORD Objective: Changes in health-related quality of life (HRQoL) were evaluated in adults with severe asthma following inhaled corticosteroid treatment with high-dose beclomethasone dipropionate or budesonide (BDP/BUD) and compared with fluticasone propionate taken at approximately half the dose of BDP/BUD. Methodology: HRQoL was assessed as part of an open, multicentre, randomized, parallel-group study in Australia evaluating the safety and efficacy of switching to fluticasone propionate (FP) 1000,2000 µg/day (n = 67) compared with remaining on BDP/BUD ,1750 µg/day (n = 66) for 6 months. Patients completed two HRQoL questionnaires, the Asthma Quality of Life Questionnaire (AQLQ) and the Medical Outcomes Study Short Form-36 (SF-36), at baseline and at weeks 12 and 24. A change in AQLQ score of ,0.5 was considered to be clinically meaningful. Results: There were significant improvements in HRQoL with FP on four of the eight dimensions on the SF-36 (i.e. physical functioning, general health, role-emotional, and mental health), while there were no significant improvements in HRQoL in the BDP/BUD group. Overall, patients in the FP group experienced significantly greater improvement (P < 0.001) in AQLQ scores at weeks 12 and 24 compared with the BDP/BUD group. On the individual domains of the AQLQ, there were significant treatment differences (P < 0.01) in favour of FP in three of the four domains (activity limitations [0.92], symptoms [0.73], and emotional function [1.02]). Mean differences between groups for overall score and these three domains were also clinically meaningful. Conclusion: Patients with severe asthma who received FP (at approximately half the dose of BDP/BUD) experienced statistically significant, as well as clinically meaningful, improvements in their HRQoL. [source] Treatment of Premature Ejaculation in the Asia-Pacific Region: Results from a Phase III Double-blind, Parallel-group Study of DapoxetineTHE JOURNAL OF SEXUAL MEDICINE, Issue 1pt1 2010Chris McMahon MBBS, FAChSHM ABSTRACT Introduction., Dapoxetine is a short-acting selective serotonin reuptake inhibitor that was recently approved for the on-demand treatment of premature ejaculation (PE). Aim., To evaluate the efficacy and safety of dapoxetine 30 mg and 60 mg on demand (prn) in men with PE from the Asia-Pacific region. Methods., This randomized, double-blind, parallel-group, placebo-controlled trial enrolled men who were 18 years or older; in a monogamous, heterosexual relationship for at least 6 months; met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision, criteria for PE for at least 6 months; and had an intravaginal ejaculatory latency time (IELT) of 2 minutes or less in at least 75% of sexual intercourse episodes. Subjects received placebo, dapoxetine 30 mg, or dapoxetine 60 mg prn (1,3 hours before intercourse) for 12 weeks. Main Outcome Measures., Stopwatch-measured Average IELT, the Premature Ejaculation Profile (PEP), Clinical Global Impression (CGI) of change in PE, treatment-emergent adverse events (TEAEs). Results., Of the 1,067 subjects randomized, 858 completed the study. Mean Average IELT increased from approximately 1.1 minutes at baseline (across groups) to 2.4, 3.9, and 4.2 minutes with placebo, dapoxetine 30 mg, and dapoxetine 60 mg, respectively, and geometric mean Average IELT increased from approximately 0.9 minutes at baseline (across groups) to 1.8, 2.7, and 3.1 minutes, respectively (fold-increases of 2.0, 2.8, and 3.3, respectively). All PEP measures and the CGI of change were significantly improved with dapoxetine vs. placebo at study endpoint (P , 0.005 for all). The most common TEAEs with dapoxetine included nausea, dizziness, somnolence, headache, vomiting, diarrhea, and nasopharyngitis; TEAEs led to discontinuation in 0.3%, 1.7%, and 5.1% of subjects with placebo, dapoxetine 30 mg, and dapoxetine 60 mg, respectively. Conclusions., Dapoxetine treatment significantly prolonged IELT and improved PEP measures and was generally well tolerated in men with PE in the Asia-Pacific region. McMahon C, Kim SW, Park NC, Chang C, Rivas D, Tesfaye F, Rothman M, and Aquilina J on behalf of the dapoxetine 3003 study investigators. Treatment of premature ejaculation in the Asia-Pacific region: Results from a phase III double-blind, parallel-group study of dapoxetine. J Sex Med 2010;7:256,268. [source] Once-Daily Prolonged-Release Tacrolimus (ADVAGRAF) Versus Twice-Daily Tacrolimus (PROGRAF) in Liver TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2010P. Trune The efficacy and safety of dual-therapy regimens of twice-daily tacrolimus (BID; Prograf) and once-daily tacrolimus (QD; Advagraf) administered with steroids, without antibody induction, were compared in a multicenter, 1:1-randomized, two-arm, parallel-group study in 475 primary liver transplant recipients. A double-blind, double-dummy 24-week period was followed by an open extension to 12 months posttransplant. The primary endpoint, event rate of biopsy-proven acute rejection (BPAR) at 24 weeks, was 33.7% for tacrolimus BID versus 36.3% for tacrolimus QD (Per-protocol set; p = 0.512; treatment difference 2.6%, 95% confidence interval ,7.3%, 12.4%), falling within the predefined 15% noninferiority margin. At 12 months, BPAR episodes requiring treatment were similar for tacrolimus BID and QD (28.1% and 24.7%). Twelve-month patient and graft survival was 90.8% and 85.6% for tacrolimus BID and 89.2% and 85.3% for tacrolimus QD. Adverse event (AE) profiles were similar for both tacrolimus BID and QD with comparable incidences of AEs and serious AEs. Tacrolimus QD was well tolerated with similar efficacy and safety profiles to tacrolimus BID. [source] Memantine and constraint-induced aphasia therapy in chronic poststroke aphasia,ANNALS OF NEUROLOGY, Issue 5 2009Marcelo L. Berthier MD Objective We conducted a randomized, double-blind, placebo-controlled, parallel-group study of both memantine and constraint-induced aphasia therapy (CIAT) on chronic poststroke aphasia followed by an open-label extension phase. Methods Patients were randomized to memantine (20mg/day) or placebo alone during 16 weeks, followed by combined drug treatment with CIAT (weeks 16,18), drug treatment alone (weeks 18,20), and washout (weeks 20,24), and finally, an open-label extension phase of memantine (weeks 24,48). After baseline evaluations, clinical assessments were done at two end points (weeks 16 and 18), and at weeks 20, 24, and 48. Outcome measures were changes in the Western Aphasia Battery-Aphasia Quotient and the Communicative Activity Log. Results Twenty-eight patients were included, and 27 completed both treatment phases. The memantine group showed significantly better improvement on Western Aphasia Battery-Aphasia Quotient compared with the placebo group while the drug was taken (week 16, p = 0.002; week 18, p = 0.0001; week 20, p = 0.005) and at the washout assessment (p = 0.041). A significant increase in Communicative Activity Log was found in favor of memantine-CIAT relative to placebo-CIAT (week 18, p = 0.040). CIAT treatment led to significant improvement in both groups (p = 0.001), which was even greater under additional memantine treatment (p = 0.038). Beneficial effects of memantine were maintained in the long-term follow-up evaluation, and patients who switched to memantine from placebo experienced a benefit (p = 0.02). Interpretation Both memantine and CIAT alone improved aphasia severity, but best outcomes were achieved combining memantine with CIAT. Beneficial effects of memantine and CIAT persisted on long-term follow-up. Ann Neurol 2009;65:577,585 [source] High versus low dosing of oral colchicine for early acute gout flare: Twenty-four,hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study,ARTHRITIS & RHEUMATISM, Issue 4 2010Robert A. Terkeltaub Objective Despite widespread use of colchicine, the evidence basis for oral colchicine therapy and dosing in acute gout remains limited. The aim of this trial was to compare low-dose colchicine (abbreviated at 1 hour) and high-dose colchicine (prolonged over 6 hours) with placebo in gout flare, using regimens producing comparable maximum plasma concentrations in healthy volunteers. Methods This multicenter, randomized, double-blind, placebo-controlled, parallel-group study compared self-administered low-dose colchicine (1.8 mg total over 1 hour) and high-dose colchicine (4.8 mg total over 6 hours) with placebo. The primary end point was ,50% pain reduction at 24 hours without rescue medication. Results There were 184 patients in the intent-to-treat analysis. Responders included 28 of 74 patients (37.8%) in the low-dose group, 17 of 52 patients (32.7%) in the high-dose group, and 9 of 58 patients (15.5%) in the placebo group (P = 0.005 and P = 0.034, respectively, versus placebo). Rescue medication was taken within the first 24 hours by 23 patients (31.1%) in the low-dose group (P = 0.027 versus placebo), 18 patients (34.6%) in the high-dose group (P = 0.103 versus placebo), and 29 patients (50.0%) in the placebo group. The low-dose group had an adverse event (AE) profile similar to that of the placebo group, with an odds ratio (OR) of 1.5 (95% confidence interval [95% CI] 0.7,3.2). High-dose colchicine was associated with significantly more diarrhea, vomiting, and other AEs compared with low-dose colchicine or placebo. With high-dose colchicine, 40 patients (76.9%) had diarrhea (OR 21.3 [95% CI 7.9,56.9]), 10 (19.2%) had severe diarrhea, and 9 (17.3%) had vomiting. With low-dose colchicine, 23.0% of the patients had diarrhea (OR 1.9 [95% CI 0.8,4.8]), none had severe diarrhea, and none had vomiting. Conclusion Low-dose colchicine yielded both maximum plasma concentration and early gout flare efficacy comparable with that of high-dose colchicine, with a safety profile indistinguishable from that of placebo. [source] Evaluation of the efficacy and safety of terguride in patients with fibromyalgia syndrome: Results of a twelve-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study,ARTHRITIS & RHEUMATISM, Issue 1 2010Oliver Distler Objective To assess the efficacy and safety of terguride, a partial dopamine agonist, in patients with fibromyalgia syndrome (FMS). Methods In a 12-week, multicenter, double-blind, placebo-controlled, parallel-group study, 99 patients were randomized at a ratio of 2 to 1 to receive terguride or placebo. Over 21 days, the dosage was titrated to a maximum daily dose of 3 mg of terguride or placebo, and this fixed dosage was continued over 9 weeks. The primary efficacy variable was the intensity of pain (100-mm visual analog scale). Secondary efficacy variables included the Fibromyalgia Impact Questionnaire (FIQ) score, the tender point score (TPS), and the Hamilton Depression Scale (HDS) score. During the study, patients were evaluated for the presence of cervical spine stenosis by magnetic resonance imaging (MRI). Results No significant differences in the change in pain intensity, FIQ score, TPS, or HDS score between baseline and 12 weeks were observed in the terguride group as compared with the placebo group. Cervical spine stenosis was detected in 22% of the patients. Only patients with cervical spine stenosis responded to terguride treatment. FIQ scores improved significantly (per-protocol analysis), and pain intensity, the TPS score, and the HDS score showed a trend toward improvement in the terguride group as compared with the placebo group. Terguride treatment was safe. Only those adverse events already known to be side effects of terguride were observed. Premature termination of the study in patients receiving terguride (26%) occurred predominantly during up-titration and in the absence of comedication for treatment of nausea. Conclusion Terguride treatment did not improve pain, the FIQ score, the TPS, or the HDS score in the total study population. However, a subgroup of patients with cervical spine stenosis seemed to benefit from terguride treatment. [source] More pronounced inhibition of cyclooxygenase 2, increase in blood pressure, and reduction of heart rate by treatment with diclofenac compared with celecoxib and rofecoxibARTHRITIS & RHEUMATISM, Issue 1 2006Burkhard Hinz Objective Recent findings suggest that permanent blockade of cyclooxygenase 2 (COX-2) is one factor contributing to the cardiovascular side effects of selective COX-2 inhibitors (coxibs) and nonsteroidal antiinflammatory drugs (NSAIDs). The present study compared the extent and time course of COX-2 inhibition and the effects on cardiovascular parameters (changes in blood pressure and heart rate) between various antirheumatic doses of diclofenac, celecoxib, and rofecoxib in healthy elderly volunteers. Methods A randomized, parallel-group study was conducted in volunteers receiving 75 mg diclofenac twice daily, 200 mg celecoxib twice daily, or 25 mg rofecoxib once daily for 8 days. Blood samples were obtained predose and at specified time points postdose, on days 1 and 8, for assay of drug plasma concentrations and COX-2 inhibition. Lipopolysaccharide-induced prostaglandin E2 synthesis was measured ex vivo as an index of COX-2 activity in human whole blood. Results COX-2 inhibition was significantly less pronounced after treatment with celecoxib and rofecoxib than with diclofenac. Maximal inhibitions after a single dose and at steady state, respectively, were as follows: 99% and 99% with diclofenac, 70% and 81% with celecoxib, and 56% and 72% with rofecoxib. At steady state, only diclofenac caused virtually complete COX-2 inhibition over the whole dose interval, and this corresponded to the highest increase in systolic blood pressure and greatest reduction in heart rate. Conclusion Diclofenac elicited the most pronounced COX-2 inhibition, blood pressure elevation, and suppression of heart rate. It is assumed that the extent and time course of intravascular COX-2 inhibition may determine the differential profile of cardiovascular side effects associated with NSAIDs and coxibs, but this has to be proven in future studies. [source] The effect of carbamazepine on the steady-state pharmacokinetics of ziprasidone in healthy volunteersBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue S1 2000J. J. Miceli Aims, To evaluate the effect of steady-state carbamazepine administration on the steady-state pharmacokinetics of ziprasidone in healthy young adults, in an open, randomised, parallel-group study. Methods, Twenty-five subjects were randomized to one of two treatment groups. Group 1 received 20 mg ziprasidone twice daily on days 1 and 2, and a single dose on day 3. A single 100 mg dose of carbamazepine was given once daily on days 5 and 6 and twice daily on days 7 and 8, followed by 200 mg twice daily until day 28 and on the morning only on day 29. Ziprasidone 20 mg was also administered twice daily on days 26 and 27 and in the morning only on day 28. Group 2 received the same treatment regimen with carbamazepine replaced by placebo. Pharmacokinetic data were obtained on days 3 and 28. Results, Nine subjects in group 1 and 10 in group 2 completed all three treatment periods (ziprasidone, carbamazepine or placebo; and ziprasidone plus carbamazepine or placebo). Carbamazepine administration to group 1 was associated with modest reductions in ziprasidone exposure, with mean decreases in ziprasidone AUC(0,12 h) and Cmax values of 36% and 27%, respectively, on day 28 compared with day 3 (P<0.03). The mean differences between day 28 and day 3 ziprasidone AUC(0,12 h) and Cmax values were also statistically significantly greater in the carbamazepine group than in the placebo group. The mean half-life of ziprasidone decreased by 1 h from day 3 to day 28 in the subjects receiving carbamazepine, compared with virtually no change in the placebo group. All adverse events were mild or moderate in severity and there were no serious adverse events, or clinically significant changes in ECGs and vital signs throughout the study. Conclusions, Induction of CYP3A4 with carbamazepine led to a modest reduction (<36%) in steady-state exposure to ziprasidone that is believed to be clinically insignificant. [source] The combination of calcipotriol and methotrexate compared with methotrexate and vehicle in psoriasis: results of a multicentre placebo-controlled randomized trialBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2003E.M.G.J. De Jong SummaryBackground A multicentre, randomized, double-blind, vehicle-controlled, parallel-group study was carried out to study the effect of the addition of calcipotriol ointment to methotrexate (MTX) therapy in patients with psoriasis vulgaris. Objectives To investigate whether the addition of calcipotriol to treatment with MTX has an MTX-sparing effect, and whether the combination of treatments is safe. Additionally, to compare the effect of calcipotriol or vehicle on the duration of the relapse-free interval after cessation of MTX. Methods Patients on maintenance therapy with MTX with controlled psoriasis were selected. The study was divided into three phases: (i) an MTX-free phase with double-blind treatment with either calcipotriol ointment or vehicle; (ii) an MTX titration phase with open MTX treatment and additional double-blind treatment with either calcipotriol or vehicle until target response; and (iii) follow-up phase: in a group of 97 patients, psoriasis was assessed using the modified psoriasis severity score, patients' assessment and safety parameters were monitored as well. Results The combined use of calcipotriol with MTX resulted in an MTX-sparing effect of 3·4 mg week,1 (phase (II) and 2·6 mg week,1 (phase I and II taken together), while still maintaining efficacy. Calcipotriol treatment increased the time to relapse of psoriasis following discontinuation of MTX: 113 days vs. 35 days. A decrease in aspartate aminotransferase and alanine aminotransferase was seen during the study of 8% (calcipotriol) and 12% (vehicle). Conclusions The combination of calcipotriol and MTX was safe and well tolerated. The combination resulted in lower cumulative dosages of MTX compared with MTX and vehicle. Therefore the risk of side-effects is substantially decreased. [source] Efficacy and safety of NT 201 for upper limb spasticity of various etiologies , a randomized parallel-group studyACTA NEUROLOGICA SCANDINAVICA, Issue 4 2010M. Barnes Barnes M, Schnitzler A, Medeiros L, Aguilar M, Lehnert-Batar A, Minnasch P. Efficacy and safety of NT 201 for upper limb spasticity of various etiologies , a randomized parallel-group study. Acta Neurol Scand: 2010: 122: 295,302. © 2010 John Wiley & Sons A/S. Objective,,, To assess efficacy and safety of two dilutions of botulinum neurotoxin type A NT 201 (Xeomin®) in patients with upper limb spasticity of diverse etiology. Methods,,, Changes in functional disability and muscle tone from baseline to week 4 after NT 201 treatment. Results,,, One hundred ninety-two patients with stroke, brain injury, multiple sclerosis, or cerebral palsy were randomized to either 50 or 20 U/ml NT 201 dilutions. The maximum total NT 201 dose was 495 units. Four weeks post-injection, a , 1-point reduction was observed on the Disability Assessment Scale in 57.1%, and on the Ashworth scale in , 62.2% of patients. The 20 U/ml NT 201 dilution was non-inferior to the 50 U/ml NT 201 dilution. Global improvement was rated high by patients (80.2%) and investigators (89.0%). Conclusions,,, NT 201 improved functional disability and muscle tone and was well tolerated in patients with upper limb spasticity of diverse etiology in both dilutions. [source] | ||||||||||||||||||||||||||||