Phase III, randomised, double-blind, placebo-controlled study of the ß3-adrenoceptor agonist mirabegron, 50 mg once daily, in Japanese patients with overactive bladder.

OBJECTIVE: To evaluate the efficacy and safety of the ß3-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/24 h and ≥1 urgency episode/24 h or ≥1 urgency incontinence episode/24 h were randomised to once-daily placebo, mirabegron 50 mg or tolterodine 4 mg (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/24 h 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 50 mg (n = 380) or tolterodine 4 mg (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/24 h (-1.67 [2.212] vs -0.86 [2.354]; P < 0.001) and mean [sd] change from baseline in number of urgency episodes/24 h (-1.85 [2.555] vs -1.37 [3.191]; P = 0.025), incontinence episodes/24 h (-1.12 [1.475] vs -0.66 [1.861]; P = 0.003), urgency incontinence episodes/24 h (-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 50 mg once daily is an effective treatment for OAB symptoms, with a low occurrence of side effects in a Japanese population.

Phase III Study to Assess Long-Term (52-Week) Safety and Efficacy of Mirabegron, a ß3 -Adrenoceptor Agonist, in Japanese Patients with Overactive Bladder.

OBJECTIVES: To investigate safety, tolerability and efficacy of long-term (52 weeks) open-label treatment with mirabegron 50 mg, with an optional dose increase to 100 mg, in patients with overactive bladder (OAB). METHODS: Patients received mirabegron 50 mg once daily for 52 weeks. If efficacy was insufficient at week 8, the dose could be increased to 100 mg. Safety was evaluated based on vital signs, adverse events (AEs), laboratory findings, electrocardiogram and post-void residual volume. Treatment efficacy was assessed with a 3-day micturition diary and the King's Health Questionnaire (KHQ). RESULTS: Two hundred and four patients were enrolled; mirabegron dose was maintained at 50 mg in 153 patients and increased to 100 mg in 50 patients. Mirabegron was well tolerated at both doses. Incidences of AEs and treatment-related AEs were 91.4% and 33.6% in patients on 50 mg, and 100% and 30.0% in patients on 100 mg, respectively. Time course changes in systolic or diastolic blood pressure and pulse rate were not considered clinically significant. At the end of treatment (EOT), patients on 50 mg and 100 mg showed improvement in frequency and urgency. Improvements from baseline to EOT in quality of life scores were observed for all KHQ domains. CONCLUSIONS: There were no safety or tolerability concerns associated with mirabegron 50 mg (with an optional dose increase to 100 mg) over 52 weeks. Improvement in micturition variables was maintained with mirabegron 50 mg from weeks 8 to 52.

Efficacy and Safety of the Selective ß3 -Adrenoceptor Agonist Mirabegron in Japanese Patients with Overactive Bladder: A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study.

OBJECTIVES: To evaluate the efficacy and safety of the ß3 -adrenoceptor agonist, mirabegron, compared with placebo in Japanese patients with overactive bladder (OAB). METHODS: 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. RESULTS: 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. CONCLUSIONS: Mirabegron demonstrated significant improvements in OAB symptoms compared with placebo and was well tolerated.