Randomized Double-blind, Active-controlled Phase 3 Study to Assess 12-Month Safety and Efficacy of Mirabegron, a β3-Adrenoceptor Agonist, in Overactive Bladder

Abstract 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 β 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) 4mg 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 4mg, 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 4mg, 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.