Mirabegron for the treatment of overactive bladder: a prespecified pooled efficacy analysis and pooled safety analysis of three randomised, double-blind, placebo-controlled, phase III studies
Article first published online: 21 MAY 2013
© 2013 Astellas Pharma Europe Ltd. International Journal of Clinical Practice published by John Wiley & Sons Ltd
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International Journal of Clinical Practice
Volume 67, Issue 7, pages 619–632, July 2013
How to Cite
Nitti, V. W., Khullar, V., van Kerrebroeck, P., Herschorn, S., Cambronero, J., Angulo, J. C., Blauwet, M. B., Dorrepaal, C., Siddiqui, E. and Martin, N. E. (2013), Mirabegron for the treatment of overactive bladder: a prespecified pooled efficacy analysis and pooled safety analysis of three randomised, double-blind, placebo-controlled, phase III studies. International Journal of Clinical Practice, 67: 619–632. doi: 10.1111/ijcp.12194
Victor Nitti is a consultant for Allergan, American Medical Systems, Astellas, Medtronic, and Uroplasty; has been reimbursed for lectures, including service on speakers’ bureaus, and for the development of educational presentations, by Allergan; and holds stock options in Serenity. His institution has received grants or has grants pending from Allergan, Astellas and Pfizer. Nancy Martin, Emad Siddiqui, Caroline Dorrepaal and Mary Beth Blauwet are employees of Astellas. Sender Herschorn is a Consultant and Clinical Trial Investigator for Astellas, Pfizer, Allergan and AMS. Javier Angulo has received educational grants for research from Astellas and Pfizer, and has received payment from Astellas, GlaxoSmithKline, and Pfizer as a lecturer/faculty. Vik Khullar has Advisory Board membership with Astellas and Pfizer; has received consultancy fees from Allergan, Astellas, and Pfizer, and grants from Astellas and Pfizer. He also has received payment for lectures from Astellas and Pfizer. Phillip van Kerrebroeck is a speaker for Astellas and Ferring. Javier Cambronero has no conflicts of interest to report.
- Issue published online: 13 JUN 2013
- Article first published online: 21 MAY 2013
- Manuscript Accepted: 20 APR 2013
- Manuscript Received: 20 FEB 2013
- Astellas Pharma Inc
To examine pooled efficacy data from three, large phase III studies comparing mirabegron (50 and 100 mg) with placebo, and pooled safety data including additional mirabegron 25 mg and tolterodine extended release (ER) 4 mg results.
This prespecified pooled analysis of three randomised, double-blind, placebo-controlled, 12-week studies, evaluated efficacy and safety of once-daily mirabegron 25 mg (safety analysis), 50 or 100 mg (efficacy and safety analyses) and tolterodine ER 4 mg (safety analysis) for the treatment of symptoms of overactive bladder (OAB). Co-primary efficacy measures were change from baseline to Final Visit in the mean number of incontinence episodes/24 h and mean number of micturitions/24 h. Key secondary efficacy end-points included mean number of urgency episodes/24 h and mean volume voided/micturitions, while other end-points included patient-reported outcomes according to the Treatment Satisfaction-Visual Analogue Scale (TS-VAS) and responder analyses [dry rate (posttreatment), ≥ 50% reduction in incontinence episodes/24 h, ≤ 8 micturitions/24 h (post hoc analysis)]. The safety analysis included adverse event (AE) reporting, laboratory assessments, ECG, postvoid residual volume and vital signs (blood pressure, pulse rate).
Mirabegron (50 and 100 mg once daily) demonstrated statistically significant improvements compared with placebo for the co-primary end-points, key secondary efficacy variables, TS-VAS and responder analyses (all comparisons p < 0.05). Mirabegron is well tolerated and demonstrates a good safety profile. The most common AEs (≥ 3%) included hypertension, nasopharyngitis and urinary tract infection (UTI); the incidence of hypertensive events and UTIs decreased with increasing dose. For mirabegron, the incidence of the bothersome antimuscarinic AE, dry mouth, was at placebo level and of a lesser magnitude than tolterodine.
The efficacy and safety of mirabegron are demonstrated in this large pooled clinical trial dataset in patients with OAB.