Solifenacin treatment in men with overactive bladder: effects on symptoms and patient-reported outcomes.

OBJECTIVE: In the few studies to evaluate antimuscarinics for overactive bladder (OAB) in men, safety has been the primary focus. In OAB efficacy trials, subject populations have been predominantly female and patient-reported outcomes (PROs) have been assessed only recently. We present a post hoc analysis of PRO-based findings from the subset of men (without presumed bladder outlet obstruction [BOO]) from two large, independent, open-label trials of solifenacin. METHODS: Subjects with OAB for > or =3 months received flexibly dosed solifenacin for 12 weeks. At baseline and 4-week intervals, subjects completed the Patient Perception of Bladder Condition (PPBC) and Overactive Bladder Questionnaire (OAB-q). In one study, subjects also completed 3-day bladder diaries. At baseline, mean PPBC scores were similar in both studies and indicative of moderate-to-severe problems. RESULTS: After 12 weeks of solifenacin, mean PPBC scores improved significantly (p < 0.0001); values were suggestive of minor-to-moderate problems. Mean scores on the OAB-q were also significantly improved after solifenacin (p values < or =0.001). In men without presumed BOO, solifenacin significantly improved PRO measures of symptom bother, health-related quality of life, and overall perception of bladder problems. CONCLUSION: Results from these two studies support the use of solifenacin as a well-tolerated and efficacious treatment option for providing symptom relief in men with OAB without BOO.

Solifenacin for overactive bladder: secondary analysis of data from VENUS based on baseline continence status.

INTRODUCTION AND HYPOTHESIS: VENUS evaluated the efficacy of solifenacin on urgency in patients with overactive bladder (OAB). We hypothesized that solifenacin would be comparably efficacious in continent and incontinent patients. METHODS: VENUS was a 12-week, placebo-controlled trial in patients with OAB. Treatment efficacy was assessed using bladder diaries and patient-reported outcome measures. The primary endpoint was the change in daily urgency episodes. Exploratory subgroup analyses were conducted using baseline continence status. RESULTS: Solifenacin reduced urgency episodes versus placebo in continent (-3.4 vs. -2.3) and incontinent patients (-4.2 vs. -2.9) and incontinence episodes (-2.1 vs. -1.2) in that subgroup; 58% versus 42% of incontinent patients receiving solifenacin versus placebo were continent at study end. In both cohorts, solifenacin- versus placebo-treated patients showed greater improvements in perceptions of urgency severity, symptom bother, and health-related quality of life. CONCLUSION: This post hoc analysis demonstrates the efficacy of solifenacin regardless of baseline continence status.

Assessment of the efficacy and safety of intravenous conivaptan in patients with euvolaemic hyponatraemia: subgroup analysis of a randomized, controlled study.

OBJECTIVE AND DESIGN: Most cases of euvolaemic hyponatraemia are associated with elevated plasma levels of AVP. Conivaptan is a high-affinity, nonpeptide vasopressin V(1A)/V(2)-receptor antagonist. We performed a subgroup analysis of a multicentre, randomized, placebo-controlled, double-blind, parallel-group study to evaluate the efficacy and safety of intravenous (i.v.) conivaptan for the treatment of euvolaemic hyponatraemia. PATIENTS: Fifty-six euvolaemic patients with serum [Na(+)] of 115 to < 130 mmol/l received conivaptan 40 or 80 mg/day or placebo via continuous i.v. infusion for 4 days. A 20-mg loading dose was administered intravenously over 30 min in the conivaptan groups; the placebo group received a placebo loading dose. MEASUREMENTS: Change in serum [Na(+)], measured by the baseline-adjusted area under the serum [Na(+)]-time curve (AUC), was the primary efficacy parameter. Secondary efficacy measures included the time from the first dose to a confirmed > or = 4 mmol/l increase in serum [Na(+)], total time with serum [Na(+)] > or = 4 mmol/l above baseline, change in serum [Na(+)] from baseline, and number of patients with a confirmed > or = 6 mmol/l increase in serum [Na(+)] or normal [Na(+)]. Safety assessments included adverse events (AE), incidence of overly rapid correction of serum [Na(+)], and changes in vital signs and electrocardiographic and clinical laboratory parameters. RESULTS: During the first 2 days of treatment, and over the entire 4-day treatment period, both conivaptan doses significantly increased the serum [Na(+)] AUC more than placebo (P < 0.01). Conivaptan 40 and 80 mg/day significantly improved all secondary efficacy measures. Conivaptan was generally well tolerated; infusion-site reaction was the most common AE. CONCLUSIONS: In hospitalized patients with euvolaemic hyponatraemia, i.v. conivaptan significantly increased serum [Na(+)] promptly and was well tolerated.

Symptom bother and health-related quality of life outcomes following solifenacin treatment for overactive bladder: the VESIcare Open-Label Trial (VOLT).

BACKGROUND: Most clinical trials designed to evaluate overactive bladder (OAB) syndrome treatments have focused on measuring micturition variables from bladder diaries. However, although diaries help physicians assess symptoms objectively, they lack information on patients' subjective experience of OAB symptoms and the effects of treatment. OBJECTIVE: The objective of this study was to assess patients' perceptions of improvements in symptom bother and health-related quality of life (HRQOL) with solifenacin succinate 5- and 10-mg treatments in patients with OAB. METHODS: VOLT (VESIcare Open-Label Trial) was a prospective, flexible-dosing trial performed at 207 centers in the United States. Ambulatory adult (aged > or = 18 years) men and women with an established diagnosis of OAB (urgency, urge urinary incontinence, frequency, and/or nocturia for > or = 3 months) and who provided a sterile urine sample received solifenacin QD for 12 weeks. Initially, all patients received 5 mg/d, with the option of adjustment to 10 mg/d at 4 and 8 weeks. Effectiveness was assessed using the Patient Perception of Bladder Condition (PPBC) scale, a visual analog scale (VAS) for the degree of bother caused by individual OAB symptoms, and the overactive bladder questionnaire (OAB-q). Assessments were performed at study initiation and study end or study termination. Adverse events (AEs) were assessed throughout. RESULTS: Patients (N = 2225) were enrolled between June 2004 and April 2005. Patients with baseline data (n = 2205) had a mean (SD) age of 59.7 (14.4) years; most patients were women (1813 [82.2%]) and white (1761 [79.9%]). Of the total patients enrolled, 1743 (78.3%) completed all 12 weeks of the study. After 12 weeks of solifenacin treatment, improvement was observed in the mean values of patient-reported perception of bladder condition. Significant change was observed on the PPBC scale from the mean baseline value to study end (4.4 vs 2.9; P < 0.001). All subscales of HRQOL significantly improved on the OAB-q score (mean changes, 14.7 to 29.6; all, P < 0.001). On the VAS, there was a significant reduction in the degree of bother associated with urgency, urge urinary incontinence, frequency, and/or nocturia (mean changes in VAS ratings, -36.7 to -41.8; all, P < 0.001 vs baseline). Solifenacin was well tolerated in most patients. Treatment-emergent AEs were reported by 1321 (59.4%) patients. Most reported AEs were anticholinergic in nature and of mild to moderate severity: dry mouth, 477 (21.4%); constipation, 295 (13.3%); headache, 76 (3.4%); blurred vision, 57 (2.6%); nausea, 39 (1.8%); dyspepsia, 34 (1.5%); and dry eye, 29 (1.3%). Two hundred sixteen (9.7%) patients discontinued treatment due to AEs. CONCLUSION: Flexibly dosed solifenacin 5 and 10 mg QD was associated with reductions in patient-reported OAB symptom bother and improvements in patients' perception of bladder condition and HRQOL.

Treatment with solifenacin increases warning time and improves symptoms of overactive bladder: results from VENUS, a randomized, double-blind, placebo-controlled trial.

OBJECTIVES: In this double-blind, placebo-controlled trial, we assessed the efficacy and tolerability of solifenacin treatment for overactive bladder (OAB) with a focus on urgency-related endpoints. Changes in number of urgency episodes were evaluated as the primary endpoint; secondary endpoints included changes in conventional diary-based OAB symptoms. We also measured warning time (defined as the time from first sensation of urgency to voiding). METHODS: We randomized patients (n = 739) to once-daily solifenacin or placebo for 12 weeks. Solifenacin 5 mg or matching placebo was administered for 4 weeks; dose could be maintained or adjusted at weeks 4 and 8. Participants completed 3-day micturition diaries at multiple study visits; warning time was recorded at baseline and week 12. RESULTS: At study end, the mean number of urgency episodes per 24 hours decreased by 3.91 (from 6.15 to 2.24) with solifenacin and by 2.73 (from 6.03 to 3.30) with placebo (P < .0001 between groups). Other diary-recorded symptoms (incontinence and micturition frequency) were also significantly more reduced with solifenacin compared with placebo. Median warning time increased 31.5 seconds (baseline, 67.8 seconds) with solifenacin, significantly longer (P = .008) than the median increase of 12.0 seconds (baseline, 65.0 seconds) observed with placebo. CONCLUSIONS: Solifenacin treatment significantly reduced episodes of urgency and other key symptoms of OAB. Solifenacin is the first antimuscarinic to demonstrate significant warning time improvement at approved dosing, as shown in a large OAB study population. This is the largest OAB clinical trial yet conducted to evaluate warning time and diary variables in the same study population.

Patient-reported most bothersome symptoms in OAB: post hoc analysis of data from a large, open-label trial of solifenacin.

INTRODUCTION AND HYPOTHESIS: In overactive bladder (OAB), subjects' most bothersome symptom (MBS) may influence treatment-related outcomes. We evaluated effects of solifenacin on patient-reported outcomes (PROs) in subjects stratified by their MBS at baseline. METHODS: In a 12-week, open-label study, the effects of solifenacin on PROs were assessed using visual analog scales (VAS), the OAB questionnaire (OAB-q), and the patient perception of bladder condition (PPBC). Statistics were descriptive. RESULTS: Subjects' baseline MBS were frequency (27%), urge urinary incontinence (UUI; 26%), urgency (23%), and nocturia (15%); VAS scores were worse for MBS. By study end, participants' MBS showed the largest solifenacin-related VAS improvements. The UUI subgroup showed the largest VAS, OAB-q, and PPBC improvements. CONCLUSIONS: Solifenacin improved overall and symptom-specific bother, HRQL, and perception of their bladder condition in MBS subgroups, with larger improvements in subjects' MBS. Those with UUI as MBS showed greater improvement in most outcomes.

Solifenacin for overactive bladder: patient-reported outcomes from a large placebo-controlled trial.

OBJECTIVE: Overactive bladder (OAB) is a prevalent, chronic condition that can negatively affect health-related quality of life (HRQL). Treatment goals are to improve symptoms and HRQL. We assessed the efficacy of solifenacin in OAB patients using several patient-reported outcome (PRO) measures, with a focus on urgency severity. Results for the primary endpoint, reductions in daily urgency episodes, and other bladder-diary variables have been recently reported. MATERIALS AND METHODS: In this 12-week multicenter trial, 739 patients (aged >or= 18 years) were randomized to flexibly dosed solifenacin (5/10 mg) or placebo. Prespecified secondary PRO measures included the Indevus Urgency Severity Scale (IUSS), Urgency Perception Scale (UPS), Patient Perception of Bladder Condition (PPBC), and Overactive Bladder Questionnaire (OAB-q). Appropriate statistical tests compared treatment-group differences in continuous and categorical data. RESULTS: In the full analysis set, patients who received solifenacin (n = 357) versus placebo (n = 350) showed significant improvements on the IUSS and UPS; treatment-group differences were 0.4 (P < 0.0001) and 0.2 (P = 0.0018), respectively. On the PPBC, significantly more patients taking solifenacin (66%) than placebo (48%) perceived fewer bladder-related problems (P < 0.0001) by week 12. On the OAB-q, solifenacin was superior to placebo for the Symptom Bother and total HRQL scales and for 3 of the 4 HRQL domains at study end (P