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 β3-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).