Effect of an ATP-sensitive potassium channel opener in subjects with overactive bladder: a randomized, double-blind, placebo-controlled study (ZD0947IL/0004).
OBJECTIVE
Improvements over existing treatment standards in overactive 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 (25mg/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.
Chapple
Christopher R
CR
Department of Urology, The Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, UK. c.r.chapple@sheffield.ac.uk
Patroneva
Albena
A
Raines
Shane R
SR
D000293:Adolescent; D000328:Adult; D000368:Aged; D004095:Dihydropyridines / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D054086:KATP Channels; D008297:Male; D008875:Middle Aged; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects* / Q000378:metabolism; D011788:Quality of Life; D012189:Retrospective Studies; D016896:Treatment Outcome; D014549:Urinary Incontinence / Q000188:drug therapy* / Q000503:physiopathology; D014563:Urodynamics / Q000187:drug effects / Q000502:physiology*
D004095:Dihydropyridines; D054086:KATP Channels; D024661:Potassium Channels, Inwardly Rectifying; C463119:ZD0947; C092520:uK-ATP-1 potassium channel