Efficacy and Safety of the Selective β3 -Adrenoceptor Agonist Mirabegron in Japanese Patients with Overactive Bladder: A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study.

Abstract

To evaluate the efficacy and safety of the β3 -adrenoceptor agonist, mirabegron, compared with placebo in Japanese patients with overactive bladder (OAB). Patients with OAB symptoms for ≥24 weeks, ≥8 micturitions/24 h on average, and ≥1 episode of urgency and/or urgency incontinence/24 h were randomized to mirabegron (25, 50 or 100 mg) or placebo for 12 weeks. The primary endpoint was change from baseline to end of study in the mean number of micturitions/24 h. Secondary endpoints included micturition variables related to urgency, incontinence, volume voided, and quality of life based on the King's Health Questionnaire (KHQ). Safety was evaluated based on adverse events (AEs), laboratory findings, vital signs, electrocardiogram, and post-void residual volume. In total, 842 patients were randomized to placebo (n = 214), mirabegron 25 mg (n = 211), 50 mg (n = 208), or 100 mg (n = 209). The primary endpoint was significantly improved in each mirabegron group compared with placebo (P < 0.001; Williams' multiple comparison test). The maximal efficacy in the primary endpoint was observed at the 50 mg dose. Significant improvements were also observed in incontinence, urgency incontinence, mean volume voided, and 3 of the 9 domains from the KHQ (incontinence impact, physical limitations, and severity measures) at each mirabegron dose. Urgency episodes decreased, and mean volume voided increased, dose-dependently. The incidence of AEs in each mirabegron dose was comparable with placebo. Mirabegron demonstrated significant improvements in OAB symptoms compared with placebo and was well tolerated.