Vibegron, a Novel Potent and Selective beta(3)-Adrenoreceptor Agonist, for the Treatment of Patients with Overactive Bladder: A Randomized, Double-blind, Placebo-controlled Phase 3 Study

Background: Vibegron is a novel, potent, and selective beta(3)-adrenoreceptor agonist for the treatment of patients with overactive bladder (OAB). Objective: To evaluate the efficacy and safety of vibegron versus placebo in Japanese OAB patients. Design, setting, and participants: Patients with OAB entered a 2-wk placebo run-in phase. Once eligibility (>= 8 micturition/d and either >= 1 urgency episodes/d or >= 1 urgency incontinence episodes/d) was confirmed, patients entered a 12-wk double-blind treatment phase. The anticholinergic imidafenacin was used as an active reference. Intervention: A total of 1232 patients were randomly assigned to one of the four 12-wk treatment groups: vibegron (50 mg or 100 mg once daily), placebo, or imidafenacin (0.1 mg twice daily). Outcome measurements and statistical analysis: The primary endpoint was change in the mean number of micturitions/d at wk 12 from baseline. The secondary endpoints were changes from baselines in OAB symptom variables (daily episodes of urgency, urgency incontinence, incontinence, and nocturia, and voided volume/micturition). Quality of life (QoL) and safety were assessed. A constrained longitudinal data analysis model was used for analysis of efficacy. Results and limitations: Patients taking vibegron 50 mg and 100 mg orally for 12 wk had significant improvements over the placebo in the primary and secondary endpoints. The proportions of patients with normalization of micturition, resolution of urgency, urgency incontinence, and incontinence were significantly greater than placebo. Vibegron significantly improved QoL, with high patient satisfaction. Incidences of drug-related adverse events with vibegron 50 mg and 100 mg were 7.6%, 5.4%, similar to placebo (5.1%), and less than imidafenacin (10.3%). Treatment was for just 12 wk and a long-term study is needed. Conclusions: The 12-wk treatment with vibegron is effective and well tolerated in patients with OAB. Patient summary: This randomized study demonstrated that vibegron is clinically useful for treatment of patients with OAB. (C) 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.