To examine pooled efficacy data from three, large phase III studies comparing mirabegron (50 and 100 mg) with placebo, and pooled safety data including additional mirabegron 25 mg and tolterodine extended release (ER) 4 mg results. This prespecified pooled analysis of three randomised, double-blind, placebo-controlled, 12-week studies, evaluated efficacy and safety of once-daily mirabegron 25 mg (safety analysis), 50 or 100 mg (efficacy and safety analyses) and tolterodine ER 4 mg (safety analysis) for the treatment of symptoms of overactive bladder (OAB). Co-primary efficacy measures were change from baseline to Final Visit in the mean number of incontinence episodes/24 h and mean number of micturitions/24 h. Key secondary efficacy end-points included mean number of urgency episodes/24 h and mean volume voided/micturitions, while other end-points included patient-reported outcomes according to the Treatment Satisfaction-Visual Analogue Scale (TS-VAS) and responder analyses [dry rate (posttreatment), ≥ 50% reduction in incontinence episodes/24 h, ≤ 8 micturitions/24 h (post hoc analysis)]. The safety analysis included adverse event (AE) reporting, laboratory assessments, ECG, postvoid residual volume and vital signs (blood pressure, pulse rate). Mirabegron (50 and 100 mg once daily) demonstrated statistically significant improvements compared with placebo for the co-primary end-points, key secondary efficacy variables, TS-VAS and responder analyses (all comparisons p < 0.05). Mirabegron is well tolerated and demonstrates a good safety profile. The most common AEs (≥ 3%) included hypertension, nasopharyngitis and urinary tract infection (UTI); the incidence of hypertensive events and UTIs decreased with increasing dose. For mirabegron, the incidence of the bothersome antimuscarinic AE, dry mouth, was at placebo level and of a lesser magnitude than tolterodine. The efficacy and safety of mirabegron are demonstrated in this large pooled clinical trial dataset in patients with OAB.

Objectives: To comprehensively evaluate the efficacy and safety of the hexanic extract of Serenoa repens ( HES r, Permixon ^® ; Pierre Fabre Médicament, Castres, France), at a dose of 320 mg daily, as monotherapy for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia ( LUTS / BPH ). Materials and methods: We conducted a systematic review and meta‐analysis of randomised controlled trials ( RCT s) and prospective observational studies in patients with LUTS / BPH identified through searches in Medline, Web of Knowledge (Institute for Scientific Information), Scopus, the Cochrane Library, and bibliographic references up to March 2017. Articles studying S. repens extracts other than Permixon were excluded. Data were collected on International Prostate Symptom Score ( IPSS ), maximum urinary flow rate (Q _max ), nocturia, quality of life, prostate volume, sexual function, and adverse drug reactions ( ADR s). Data obtained from RCT s and observational studies were analysed jointly and separately using a random effects model. A sub‐group analysis was performed of studies that included patients on longer‐term treatment (≥1 year). Results: Data from 27 studies (15 RCT s and 12 observational studies) were included for meta‐analysis (total N = 5 800). Compared with placebo, the HES r was associated with 0.64 (95% confidence interval [ CI ] −0.98 to −0.31) fewer voids/night ( P < 0.001) and an additional mean increase in Q _max of 2.75 mL/s (95% CI 0.57 to 4.93; P = 0.01). When compared with α‐blockers, the HES r showed similar improvements on IPSS (weighted mean difference [ WMD ] 0.57, 95% CI −0.27 to 1.42; P = 0.18) and a comparable increase in Q _max to tamsulosin ( WMD −0.02, 95% CI −0.71 to 0.66; P = 0.95). Efficacy assessed using the IPSS was similar after 6 months of treatment between the HES r and 5α‐reductase inhibitors (5 ARI s). Analysis of all available published data for the HES r showed a mean improvement in IPSS from baseline of −5.73 points (95% CI −6.91 to −4.54; P < 0.001). HES r did not negatively affect sexual function and no clinically relevant effect was observed on prostate‐specific antigen. Prostate volume decreased slightly. Similar efficacy results were seen in patients treated for ≥1 year ( n = 447). The HES r had a favourable safety profile, with gastrointestinal disorders being the most frequent ADR (mean incidence of 3.8%). Conclusion: The present meta‐analysis, which includes all available RCT s and observational studies, shows that the HES r (Permixon) reduced nocturia and improved Q _max compared with placebo and had a similar efficacy to tamsulosin and short‐term 5‐ ARI in relieving LUTS . HES r (Permixon) appears to be an efficacious and well‐tolerated therapeutic option for the long‐term medical treatment of LUTS / BPH .