Chapple, C.R. orcid.org/0000-0002-2960-9931, Dvorak, V., Radziszewski, P. et al. (9 more authors) (2013) A phase II dose-ranging study of mirabegron in patients with overactive bladder. International Urogynecology Journal, 24 (9). pp. 1447-1458. ISSN 0937-3462
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 dosedependent reductions (improvements) from baseline to end-oftreatment 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2013. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
Keywords: | beta(3)-adrenoceptor agonist; Mirabegron; Overactive; Urinary bladder |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 02 May 2017 13:38 |
Last Modified: | 02 May 2017 13:38 |
Published Version: | http://doi.org/10.1007/s00192-013-2042-x |
Status: | Published |
Publisher: | Springer Verlag |
Refereed: | Yes |
Identification Number: | 10.1007/s00192-013-2042-x |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:115353 |