Effect of an ATP-sensitive potassium channel opener in subjects with overactive bladder: A randomized, double-blind, placebo-controlled study (ZD0947IL/0004)

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.