Effect of an ATP-sensitive potassium channel opener in subjects with overactive bladder: A randomized, double-blind, placebo-controlled study (ZD0947IL/0004)
Effect of an ATP-sensitive potassium channel opener in subjects with overactive bladder: A randomized, double-blind, placebo-controlled study (ZD0947IL/0004)
复制标题
DOI：
10.1016/j.eururo.2006.01.037
复制
发表时间：
2006-05-01
期刊：
影响因子：
23.4
通讯作者：
Raines, SR
中科院分区：
文献类型：
--
作者：
Chapple, CR;Patroneva, A;Raines, SR
目的：改善过度活动性膀胱(OAB)的现有治疗标准可能只有通过开发通过非胆碱能途径发挥作用的药物才有可能。这是首次完整报道使用钾通道开放剂治疗OAB的临床研究。方法：这项随机、双盲、安慰剂对照的II期研究评估了ZD0947(每天25 mg，持续12周)对OAB患者的疗效和安全性。主要终点是每24小时每次排尿的平均排尿量。关键的次要终点是每24小时平均排尿次数(总的、自愿的和失禁的)较基线的变化。结果：在主要或次要疗效变量方面，ZD0947并不优于安慰剂。ZD0947的安慰剂调整效应大小(约4毫升)低于胆碱能拮抗剂的历史数据(约.20毫升)。治疗总体安全，耐受性良好。结论：ZD0947的数据令人失望。需要更多的研究来推进OAB的新的、非胆碱能疗法的鉴定。(C)2006爱思唯尔B.V.保留所有权利。
Objectives: Improvements over existing treatment standards in over-active bladder (OAB) may only be possible through the development of drugs acting via non-cholinergic pathways. This is the first clinical study to be reported in full for the use of a potassium channel opener in OAB.Methods: This randomized, double-blind, placebo -controlled phase II study evaluated the efficacy and safety of ZD0947 (25 mg/day for 12 weeks) in patients with OAB. The primary endpoint was mean volume voided per micturition per 24 hours. Key secondary endpoints were changes from baseline in mean numbers of micturition episodes (total, voluntary, and incontinent) per 24 hours.Results: ZD0947 was not superior to placebo for the primary or secondary efficacy variables. The placebo- adjusted magnitude of effect for ZD0947 (approx. 4 mL) was less than the historic data for cholinergic antagonists (approx. 20 ml,). Treatment was generally safe and well tolerated.Conclusions: The data for ZD0947 are disappointing. More studies are needed to advance the identification of novel, non-cholinergic therapies for OAB. (c) 2006 Elsevier B.V. All rights reserved.