A phase II dose-ranging study of mirabegron in patients with overactive bladder

Christopher R. Chapple*, Vladimir Dvorak, Pjotr Radziszewski, Philip Van Kerrebroeck, Jean Jacques Wyndaele, Brigitte Bosman, Peter Boerrigter, Ted Drogendijk, Arwin Ridder, Ingrid Van der Putten-Slob, Osamu Yamaguchi

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Mirabegron is a potent and selective beta(3)-adrenoceptor agonist that may represent an alternative treatment option in place of antimuscarinics for patients with overactive bladder. 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. 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 a parts per thousand currency signaEuro parts per thousand 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. 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.
Original languageEnglish
Pages (from-to)1447-1458
JournalInternational Urogynecology Journal
Volume24
Issue number9
DOIs
Publication statusPublished - Sep 2013

Keywords

  • beta(3)-adrenoceptor agonist
  • Mirabegron
  • Overactive
  • Urinary bladder

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