Abstract
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).
Keywords
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Article Info
Publication History
Published online: October 24, 2018
Accepted:
October 2,
2018
Associate Editor: Maarten Albersen Statistical Editor: Andrew VickersFootnotes
☆Please visit www.eu-acme.org/europeanurology to read and answer questions on-line. The EU-ACME credits will then be attributed automatically.
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© 2018 Merck Sharp & Dohme Corp and The Authors. Published by Elsevier B.V. on behalf of European Association of Urology
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