A phase II dose-ranging study of mirabegron in patients with overactive bladder
Chapple CR, Dvorak V, Radziszewski P, Van Kerrebroeck P, Wyndaele JJ, Bosman B, Boerrigter P, Drogendijk T, Ridder A, Van Der Putten-Slob I, Yamaguchi O; On behalf of the Dragon Investigator Group. Int Urogynecol J. 2013 Mar 8. [Epub ahead of print]

Source

Department of Urology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Glossop Road, Sheffield, S10 2JF, UK, c.r.chapple@shef.ac.uk.

Abstract

INTRODUCTION AND HYPOTHESIS:

Mirabegron is a potent and selective β3-adrenoceptor agonist that may represent an alternative treatment option in place of antimuscarinics for patients with overactive bladder.

METHODS:

Patients completed a single-blinded, 2-week placebo run-in period followed by 12 weeks of randomized (n = 928) double-blinded treatment with mirabegron oral controlled absorption system (OCAS) 25, 50, 100, or 200 mg once-daily (QD), placebo or tolterodine extended release (ER) 4 mg QD. The primary endpoint was change from baseline to end-of-treatment in mean number of micturition episodes/24 h. Secondary endpoints included changes in mean volume voided per micturition; mean number of urinary incontinence, urgency urinary incontinence, and urgency episodes/24 h; severity of urgency; nocturia; and quality of life measures. Safety parameters included vital signs, adverse events, laboratory tests, electrocardiogram measurements and post-void residual volume.

RESULTS:

Mirabegron 25, 50, 100, and 200 mg resulted in dose-dependent reductions (improvements) from baseline to end-of-treatment in micturition frequency of 1.9, 2.1, 2.1, and 2.2 micturitions/24 h respectively, versus 1.4 micturitions/24 h with placebo (p ≤ 0.05 for the mirabegron 50-, 100-, and 200-mg comparisons). There was a statistically significant improvement with mirabegron compared with placebo for most secondary endpoints including quality of life variables. While there was a significant (p < 0.05) increase from baseline in pulse rate in the mirabegron 100-mg and 200-mg groups, this was not associated with an increased incidence of cardiovascular adverse events.

CONCLUSIONS:

The favorable efficacy and tolerability of mirabegron in this phase II dose-finding study has led to its successful advancement into a phase III clinical development program.