International Phase III, Randomized, Double-Blind, Placebo- and Active-Controlled Study to Evaluate the Safety and Efficacy of Vibegron in Patients with Symptoms of Overactive Bladder: EMPOWUR.

To assess efficacy, safety, and tolerability of vibegron, a novel, potent, highly selective β3-adrenoceptor agonist, administered 12 weeks at 75 mg once-daily to patients with overactive bladder in an international phase III trial with placebo and active control.

Adult patients with overactive bladder with ≥8.0 micturitions/day were randomized 5:5:4 to vibegron 75 mg, placebo, or extended-release tolterodine 4 mg. Up to 25% of patients could have dry overactive bladder (<1.0 urge-incontinence episodes/day). Patients completed 7-day voiding diaries at baseline and weeks 2, 4, 8, and 12.

Of 1,518 randomized patients, 90.4% completed the trial. At 12 weeks, micturitions decreased by an adjusted mean of 1.8 episodes/day for vibegron versus 1.3 for placebo (p<0.001; co-primary endpoint), and 1.6 for tolterodine. Among incontinent patients, urge-incontinence episodes decreased by an adjusted mean 2.0 episodes/day for vibegron versus 1.4 for placebo (p<0.0001; co-primary endpoint), and 1.8 for tolterodine. Moreover, vibegron was statistically significantly superior to placebo for key secondary measures of number of urgency episodes, volume per micturition, and proportion of incontinent patients with a ≥75% reduction in urge-incontinence episodes (all p<0.01). Among vibegron-treated patients, 1.7% discontinued treatment because of adverse events, versus 1.1% for placebo and 3.3% for tolterodine. Incidence of hypertension was 1.7% for vibegron and for placebo.

Once-daily vibegron 75 mg provided statistically significant reductions in micturitions, urgency episodes, urge incontinence, and increased the volume per micturition. Treatment was well-tolerated, with a favorable safety profile.

The Journal of urology. 2020 Feb 18 [Epub ahead of print]

David Staskin, Jeffrey Frankel, Susann Varano, Denise Shortino, Rachael Jankowich, Paul N Mudd

Tufts University School of Medicine, Boston, Massachusetts., Seattle Urology Research Center, Seattle, Washington., Clinical Research Consulting, Milford, Connecticut., Urovant Sciences, Irvine, California.