Vibegron (RVT-901/MK-4618/KRP-114V) Administered Once Daily as Monotherapy or Concomitantly with Tolterodine in Patients with an Overactive Bladder: A Multicenter, Phase IIb, Randomized, Double-blind, Controlled Trial

Background: Antimuscarinics have shown modest efficacy with unwanted side effects in patients with overactive bladder (OAB). Efficacy of vibegron, a new beta 3-adrenergic receptor agonist, for OAB is unknown. Objective: To evaluate the efficacy of once-daily oral vibegron in OAB patients (primary), and its safety, tolerability, and efficacy when administered alone or concomitantly with tolterodine (secondary). Design, setting, and participants: International, phase IIb, randomized, double-blind, placebo- and active comparator-controlled, two-part superiority trial (2011-2013) in OAB-wet or OAB-dry patients aged 18-75 yr (NCT01314872). Interventions: Part 1: once-daily oral vibegron monotherapy (3 [V3], 15 [V15], 50 [V50], or 100 [V100] mg), tolterodine extended release 4 mg (TER4), or placebo for 8 wk, or combination V50/TER4 for 4 wk and then V50 for 4 wk; part 2: V100/TER4, V100, TER4, or placebo for 4 wk. Outcome measurements and statistical analysis: Average daily micturitions at week 8 of part 1 (primary); urge incontinence episodes, total incontinence episodes, and urgency episodes (secondary). Results and limitations: Overall, 1395 patients were randomized. From baseline to week 8, V50 and V100 significantly decreased average daily micturitions (least square mean difference [95% confidence interval], -0.64 [-1.11, -0.18]; p = 0.007 and -0.91 [-1.37, -0.44]; p < 0.001, respectively) and the number of urge incontinence episodes (-0.72 [-1.11, -0.33] and -0.71 [-1.10, -0.32], respectively; both p < 0.001) versus placebo. All vibegron doses were well tolerated. The incidence of dry mouth was higher with TER4 than with vibegron monotherapy. Results are limited by the relatively short treatment duration. Conclusions: Once-daily V50 and V100 improved OAB symptoms; vibegron was well tolerated as monotherapy and concomitantly with tolterodine. Further development is warranted. Patient summary: Antimuscarinics, commonly used to treat overactive bladder, produce modest efficacy and unwanted side effects. In this study, a different type of drug (vibegron) was efficacious and safe, alone or with an antimuscarinic (tolterodine). (C) 2018 Merck Sharp & Dohme Corp and The Authors. Published by Elsevier B.V. on behalf of European Association of Urology