Onset of action of the β3-adrenoceptor agonist, mirabegron, in Phase II and III clinical trials in patients with overactive bladder.
OBJECTIVE
Long-term persistence with pharmacotherapy for overactive bladder (OAB) requires a drug with an early onset of action and good efficacy and tolerability profile. Although antimuscarinics improve OAB symptoms within 1-2 weeks of initiating treatment, adherence after 3 months is relatively poor due to bothersome side effects (e.g., dry mouth and constipation). Mirabegron, a β3-adrenoceptor agonist, has demonstrated significant improvements in key symptoms of OAB and good tolerability after 12 weeks in Phase III studies.


METHODS
This was a prespecified pooled analysis of three randomized, double-blind, placebo-controlled, 12-week studies, and a Phase II study, to evaluate efficacy and tolerability of mirabegron 25 and 50 mg versus placebo. The main efficacy endpoints were change from baseline to week 1 (Phase II only), week 4, and final visit in mean number of incontinence episodes/24 h, micturitions/24 h, and mean volume voided/micturition (MVV).


RESULTS
A significant benefit for mirabegron 25 and 50 mg versus placebo was evident at the first assessment point, 4 weeks after initiation of therapy, in Phase III studies for incontinence, micturitions, and MVV. The earliest measured benefit was after 1 week, in the Phase II study. Quality-of-life parameters also significantly improved with mirabegron 25 and 50 mg as early as week 4. Significant benefits continued throughout the studies. Mirabegron was well tolerated.


CONCLUSIONS
The early onset of action and good overall efficacy and tolerability balance that mirabegron offers may lead to high rates of persistence with mirabegron in the long-term treatment of OAB.
Department of Urology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Glossop Road, Sheffield, UK, c.r.chapple@shef.ac.uk.
Christopher R
CR
Chapple
Victor W
VW
Nitti
Vik
V
Khullar
Jean Jacques
JJ
Wyndaele
Sender
S
Herschorn
Philip
P
van Kerrebroeck
Mary Beth
MB
Blauwet
Emad
E
Siddiqui
D000083:Acetanilides / Q000627:therapeutic use*; D058667:Adrenergic beta-3 Receptor Agonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D013844:Thiazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D053201:Urinary Bladder, Overactive / Q000150:complications / Q000188:drug therapy*; D055815:Young Adult
D000083:Acetanilides; D058667:Adrenergic beta-3 Receptor Agonists; D013844:Thiazoles; C520025:mirabegron