Phase III, randomised, double-blind, placebo-controlled study of the β3-adrenoceptor agonist mirabegron, 50 mg once daily, in Japanese patients with overactive bladder.

Objective To evaluate the efficacy and safety of the 3-adrenoceptor agonist mirabegron, in a Japanese population with overactive bladder (OAB). Patients and Methods This randomised, double-blind, placebo-controlled phase III study enrolled adult patients experiencing OAB symptoms for 24 weeks. Patients with 8 micturitions/24h and 1 urgency episode/24h or 1 urgency incontinence episode/24h were randomised to once-daily placebo, mirabegron 50mg or tolterodine 4mg (as an active comparator, without testing for non-inferiority of efficacy and safety) for 12 weeks. The primary endpoint was the change in the mean number of micturitions/24h from baseline to final assessment. Secondary endpoints included micturition variables related to urgency and/or incontinence and quality-of-life domain scores on the King's Health Questionnaire. Safety assessments included adverse events (AEs), post-void residual urine volume, laboratory variables, vital signs and 12-lead electrocardiogram. Results A total of 1139 patients were randomised to receive placebo (n = 381), mirabegron 50mg (n = 380) or tolterodine 4mg (n = 378). Demographic and baseline characteristics were similar among the treatment groups. At final assessment, mirabegron was significantly superior to placebo in terms of mean [sd] change from baseline in number of micturitions/24h (-1.67 [2.212] vs -0.86 [2.354]; P < 0.001) and mean [sd] change from baseline in number of urgency episodes/24h (-1.85 [2.555] vs -1.37 [3.191]; P = 0.025), incontinence episodes/24h (-1.12 [1.475] vs -0.66 [1.861]; P = 0.003), urgency incontinence episodes/24h (-1.01 [1.338] vs -0.60 [1.745]; P = 0.008), and volume voided/micturition (24.300 [35.4767] vs 9.715 [29.0864] mL; P < 0.001). The incidence of AEs in the mirabegron group was similar to that in the placebo group. Most AEs were mild and none were severe. Conclusions Mirabegron 50mg once daily is an effective treatment for OAB symptoms, with a low occurrence of side effects in a Japanese population.