Efficacy and Tolerability of Mirabegron, a β3-Adrenoceptor Agonist, in Patients with Overactive Bladder: Results from a Randomised European-Australian Phase 3 Trial

Background: Mirabegron, a beta(3)-adrenoceptor agonist, has been developed for the treatment of overactive bladder (OAB). Objective: To assess the efficacy and tolerability of mirabegron versus placebo. Design, setting, and participants: Multicenter randomised double-blind, parallel-group placebo-and tolterodine-controlled phase 3 trial conducted in 27 countries in Europe and Australia in patients >= 18 yr of age with symptoms of OAB for >= 3 mo. Intervention: After a 2-wk single-blind placebo run-in period, patients were randomised to receive placebo, mirabegron 50 mg, mirabegron 100 mg, or tolterodine extended release 4 mg orally once daily for 12 wk. Outcome measurements and statistical analysis: Patients completed a micturition diary and quality-of-life (QoL) assessments. Co-primary efficacy end points were change from baseline to final visit in the mean number of incontinence episodes and micturitions per 24 h. The primary comparison was between mirabegron and placebo with a secondary comparison between tolterodine and placebo. Safety parameters included adverse events (AEs), laboratory assessments, vital signs, electrocardiograms, and postvoid residual volume. Results and limitations: A total of 1978 patients were randomised and received the study drug. Mirabegron 50-mg and 100-mg groups demonstrated statistically significant improvements (adjusted mean change from baseline [95% confidence intervals]) at the final visit in the number of incontinence episodes per 24 h (-1.57 [-1.79 to -1.35] and -1.46 [-1.68 to -1.23], respectively, vs placebo -1.17 [-1.39 to -0.95]) and number of micturitions per 24 h (-1.93 [-2.15 to -1.72] and -1.77 [-1.99 to -1.56], respectively, vs placebo -1.34 [-1.55 to -1.12]; p < 0.05 for all comparisons). Statistically significant improvements were also observed in other key efficacy end points and QoL outcomes. The incidence of treatment-emergent AEs was similar across treatment groups. The main limitation of this study was the short (12-wk) duration of treatment. Conclusions: Mirabegron represents a new class of treatment for OAB with proven efficacy and good tolerability. Trial identification: This study is registered at ClinicalTrials.gov, identifier NCT00689104. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved.