Efficacy and Safety of Once-Daily Vibegron for Treatment of Overactive Bladder in Patients Aged ≥65 and ≥75 Years: Subpopulation Analysis from the EMPOWUR Randomized, International, Phase III Study

Drugs Aging. 2021 Feb;38(2):137-146. doi: 10.1007/s40266-020-00829-z. Epub 2021 Jan 20.

Abstract

Background: Overactive bladder (OAB) is common among older adults. The efficacy and safety of vibegron for the treatment of OAB were demonstrated in the international, phase III EMPOWUR trial. This subpopulation analysis from EMPOWUR assessed the efficacy and safety of vibegron in patients aged ≥ 65 and ≥ 75 years.

Methods: In EMPOWUR, patients with OAB were randomly assigned 5:5:4 to receive once-daily vibegron 75 mg, placebo, or tolterodine 4 mg extended release, respectively, once daily for 12 weeks. Coprimary efficacy endpoints were change from baseline at week 12 in average daily number of micturitions and urge urinary incontinence (UUI) episodes; a key secondary efficacy endpoint was change from baseline at week 12 in average daily number of urgency episodes. Safety was assessed through adverse events (AEs). Efficacy analyses compared vibegron with placebo; no efficacy comparisons were made between vibegron and tolterodine.

Results: Of the 1463 patients with evaluable efficacy data, 628 patients were aged ≥ 65 years, and 179 were aged ≥ 75 years. After 12 weeks, patients treated with once-daily vibegron 75 mg in both age subgroups showed significant improvements from baseline versus placebo in all three symptoms of OAB: daily micturitions (≥ 65 years, P < 0.0001; ≥75 years, P < 0.05), UUI episodes (≥ 65 years, P < 0.001; ≥ 75 years, P < 0.0001), and urgency episodes (≥ 65 years, P < 0.01; ≥ 75 years, P < 0.01). Significant reductions from baseline versus placebo in daily micturitions, UUI episodes, and urgency episodes were observed beginning at week 2 for patients aged ≥ 65 years treated with vibegron. In patients aged ≥ 65 years, 50.0% of those receiving vibegron versus 29.8% receiving placebo experienced a ≥ 75% reduction in UUI episodes at week 12 (P < 0.0001). Rates of cardiovascular-associated AEs were low for patients receiving vibegron (<2% of patients in either age subgroup) and similar to rates in patients receiving placebo. In patients aged ≥ 65 years, hypertension was reported by 1.2%, 3.1%, and 2.9% of patients receiving vibegron, placebo, and tolterodine, respectively; in patients aged ≥ 75 years, hypertension was reported by 1.3%, 3.3%, and 2.1%, respectively.

Conclusions: In this subpopulation analysis of patients with OAB aged ≥ 65 and ≥ 75 years from the EMPOWUR study, once-daily vibegron 75 mg showed rapid onset and robust efficacy versus placebo and was generally safe and well tolerated, consistent with results from the overall population.

Trial registration: ClinicalTrials.gov identifier NCT03492281; registered April 10, 2018.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Double-Blind Method
  • Humans
  • Pyrimidinones
  • Pyrrolidines
  • Treatment Outcome
  • Urinary Bladder, Overactive* / drug therapy

Substances

  • N-(4-((5-(hydroxy(phenyl)methyl)pyrrolidin-2-yl)methyl)phenyl)-4-oxo-4,6,7,8-tetrahydropyrrolo(1,2-a)pyrimidine-6-carboxamide
  • Pyrimidinones
  • Pyrrolidines

Associated data

  • ClinicalTrials.gov/NCT03492281