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-猫眼课题宝

DOI：

10.1016/j.eururo.2018.10.006

发表时间：

2019-02-01

期刊：

EUROPEAN UROLOGY

影响因子：

23.4

通讯作者：

中科院分区：

医学1区

文献类型：

作者：

Mitcheson, Henry D.;Samanta, Suvajit;Frenkl, Tara L.

背景：抗膀胱癌药物在膀胱过度活动症(OAB)患者中显示出温和的疗效和不良的副作用。Vibegron是一种新的β3-肾上腺素能受体激动剂，对OAB的疗效尚不清楚。目的：评价每日一次口服Vibegron对OAB患者(初级)的疗效，以及单独或联合应用托特罗定(二级)时的安全性、耐受性和有效性。设计、背景和参与者：国际，IIb期，随机、双盲、安慰剂和积极对照对照的两部分优势试验(2011-2013)，用于18-75岁的OAB湿性或干性患者(NCT01314872)。干预：第1部分：每日一次口服Vibegron治疗(3[V3]，15[V15]，[V15])50[V50]，或100[V100]mg)，托特罗定缓释片4 mg(TER4)，或安慰剂治疗8wk，或联合V50/TER4治疗4wk，然后V50治疗4wk；第二部分：V100/TER4，V100，TER4，或安慰剂，为期4周。结果测量和统计分析：第一部分(初级)第8周的平均每日尿量；急迫性尿失禁发作，总尿失禁发作，和急迫性尿失禁发作(次级)。结果和限制：总共有1395名患者被随机分组。从基线到第8周，V50和V100显著降低了平均每日排尿次数(最小二乘均差[95%可信区间]，-0.64[-1.11，-0.18]；p=0.007和-0.91[-1.37，-0.44]；p&lt；0.001)和急迫性尿失禁次数(分别为-0.72[-1.11，-0.33]和-0.71[-1.10，-0.32]；p&lt；0.001)与安慰剂对比。所有Vibegron剂量均耐受性良好。TER4组口干发生率高于单用Vibegron组。结论：每日1次的V50和V100可明显改善OAB症状，单用Vibegron与托特罗定联合用药耐受性良好。患者总结：通常用于治疗膀胱过度活动症的抗霉菌药物疗效不大，副作用也不大。在这项研究中，另一种不同类型的药物(Vibegron)是有效和安全的，无论是单独使用还是与抗心肌梗死药(托特罗定)一起使用。(C)2018年默克·夏普·多姆公司和作者。爱思唯尔公司代表欧洲泌尿学协会出版

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

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

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