Efficacy and Safety of Vibegron for Persistent Symptoms of Overactive Bladder in Men Being Pharmacologically Treated for Benign Prostatic Hyperplasia: Results From the Phase 3 Randomized Controlled COURAGE Trial

J Urol. 2024 Aug;212(2):256-266. doi: 10.1097/JU.0000000000003999. Epub 2024 May 6.

Abstract

Purpose: The efficacy and safety of vibegron, a β3-adrenergic receptor agonist, was assessed among men with symptoms of overactive bladder (OAB) receiving pharmacologic treatment for benign prostatic hyperplasia (BPH) in a phase 3 randomized controlled trial.

Materials and methods: Men ≥ 45 years with OAB symptoms and BPH, treated with α-blocker with/without 5α-reductase inhibitors, were randomized 1:1 to vibegron or placebo for 24 weeks. Coprimary end points were change from baseline at week 12 in mean daily micturitions and urgency episodes. Secondary end points were change from baseline at week 12 in mean nightly nocturia and daily urge urinary incontinence episodes, International Prostate Symptom Score‒storage score, and volume voided per micturition. Safety was evaluated via adverse events (AEs).

Results: Of 1105 participants randomized, 965 (87.3%) completed the trial. At week 12, vibegron was associated with significant reductions vs placebo in daily micturitions (least squares mean difference [95% CI], -0.74 [-1.02, -0.46]; P < .0001) and urgency episodes (-0.95 [-1.37, -0.54]; P < .0001). Vibegron was also associated with significant improvements vs placebo at week 12 in nocturia episodes (least squares mean difference, -0.22 [-0.36, -0.09]; P = .002), urge urinary incontinence episodes (-0.80 [-1.33, -0.27]; P = .003), International Prostate Symptom Score‒storage scores (-0.9 [-1.2, -0.6]; P < .0001), and volume voided (15.07 mL [9.13-21.02]; P < .0001). AE rates were similar in vibegron (45.0%) and placebo (39.0%) arms; AEs occurring in ≥ 2% of participants were hypertension (9.0% vs 8.3%), COVID-19 (4.0% vs 3.1%), UTI (2.5% vs 2.2%), and hematuria (2.0% vs 2.5%).

Conclusions: In this trial, vibegron met all primary and secondary end points and was safe and well tolerated in men with OAB symptoms and pharmacologically treated BPH.

Keywords: anticholinergics; benign prostatic hyperplasia; beta-3 adrenergic agonist; overactive bladder.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase III
  • Multicenter Study

MeSH terms

  • 5-alpha Reductase Inhibitors / adverse effects
  • 5-alpha Reductase Inhibitors / therapeutic use
  • Adrenergic alpha-Antagonists / therapeutic use
  • Adrenergic beta-3 Receptor Agonists* / administration & dosage
  • Adrenergic beta-3 Receptor Agonists* / adverse effects
  • Adrenergic beta-3 Receptor Agonists* / therapeutic use
  • Aged
  • Double-Blind Method
  • Drug Therapy, Combination
  • Humans
  • Male
  • Middle Aged
  • Prostatic Hyperplasia* / complications
  • Prostatic Hyperplasia* / drug therapy
  • Pyrimidinones / administration & dosage
  • Pyrimidinones / adverse effects
  • Pyrimidinones / therapeutic use
  • Pyrrolidines / administration & dosage
  • Pyrrolidines / adverse effects
  • Pyrrolidines / therapeutic use
  • 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
  • Adrenergic beta-3 Receptor Agonists
  • Pyrimidinones
  • Pyrrolidines
  • 5-alpha Reductase Inhibitors
  • Adrenergic alpha-Antagonists