A Proof-of-Concept Study: Mirabegron, a New Therapy for Overactive Bladder

AimsTo evaluate the potential of mirabegron, a selective 3-adrenoceptor agonist, for treatment of overactive bladder (OAB) symptoms. MethodsA multicenter, randomized, double-blind, double-dummy, parallel group, placebo and active-controlled, Phase 2, proof-of-concept study was conducted. Eligible patients (n=314) were enrolled into a single-blind, 2-week placebo run-in period followed by a randomized, double-blind, placebo-controlled treatment period. Patients received mirabegron 100 or 150mg twice-daily (BID), placebo or tolterodine 4mg extended release (ER) once-daily for 4 weeks. Primary endpoint was change from baseline to end-of-treatment in mean number of micturition episodes per 24hr. Secondary endpoints included changes in mean volume voided per micturition; mean number of urinary incontinence, urgency urinary incontinence, and urgency episodes per 24hr; severity of urgency; nocturia, and quality of life measures. Safety parameters included adverse events, laboratory tests, electrocardiogram parameters and post-void residual volume. ResultsMirabegron 100 and 150mg BID resulted in a statistically significant improvement versus placebo in mean change from baseline to end-of-treatment in the primary endpoint of micturition frequency (2.2micturitions/24hr vs. 1.2micturitions/24hr for both doses, adjusted P0.01 for both comparisons). Mirabegron had a statistically significant effect versus placebo for most secondary endpoints, including quality of life variables. Despite a small increase in pulse rate, mirabegron demonstrated good safety and tolerability. ConclusionsMirabegron was efficacious and well tolerated in patients with OAB symptoms and heralds the first of a new class of oral pharmacological therapy for OAB for more than 30 years. Neurourol. Urodynam. 32:1116-1122, 2013. (c) 2013 Wiley Periodicals, Inc.