Randomized double-blind, active-controlled phase 3 study to assess 12-month safety and efficacy of mirabegron, a ß(3)-adrenoceptor agonist, in overactive bladder.

BACKGROUND: Despite several antimuscarinic treatment options for overactive bladder (OAB), there is still a need for distinct treatment approaches to manage this condition. Mirabegron, a ß(3)-adrenoceptor agonist, has demonstrated efficacy and tolerability for up to 12 wk in phase 3 trials. OBJECTIVE: To assess the 12-mo safety and efficacy of mirabegron. DESIGN, SETTING, AND PARTICIPANTS: Patients ≥ 18 yr of age with OAB symptoms for ≥ 3 mo. INTERVENTIONS: After a 2-wk single-blind placebo run-in, patients with eight or more micturitions per 24h and three or more urgency episodes in a 3-d micturition diary were randomized 1:1:1 to once-daily mirabegron 50mg, mirabegron 100mg, or tolterodine extended release (ER) 4 mg for 12 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary variable: incidence and severity of treatment-emergent AEs (TEAEs). Secondary variables: change from baseline at months 1, 3, 6, 9, and 12 in key OAB symptoms. RESULTS AND LIMITATIONS: A total of 812, 820, and 812 patients received mirabegron 50mg, mirabegron 100mg, and tolterodine ER 4 mg, respectively. Baseline demographic and OAB characteristics were similar across groups. TEAEs were reported in 59.7%, 61.3%, and 62.6% of patients, respectively; most were mild or moderate. Serious TEAEs were reported in 5.2%, 6.2%, and 5.4% of patients, respectively. The most common TEAEs were similar across groups. Dry mouth was reported by 2.8%, 2.3%, and 8.6% of patients, respectively. Adjusted mean changes from baseline to final visit in morning systolic blood pressure were 0.2, 0.4, and -0.5mm Hg for mirabegron 50mg, 100mg, and tolterodine ER 4 mg, respectively. Mirabegron and the active control, tolterodine, improved key OAB symptoms from the first measured time point of 4 wk, and efficacy was maintained throughout the 12-mo treatment period. The study was not placebo controlled, which was a limitation. CONCLUSIONS: The safety and tolerability of mirabegron was established over 1 yr, with sustained efficacy observed over this treatment period. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00688688.