Efficacy and Safety of Mirabegron Add-on Therapy to Solifenacin in Incontinent Overactive Bladder Patients with an Inadequate Response to Initial 4-Week Solifenacin Monotherapy: A Randomised, Double-blind, Multicentre, Phase 3b Study (BESIDE)

Marcus Drake, Christopher Chapple, Ahmet Esen, Stavros Athanasiou, Javier Cambronero, David Mitcheson, Sender Herschorn, Tahir Saleem, Moses Huang, Emad Siddiqi, Matthias Stölzel, Claire Herholdt, Scott MacDiarmid

Research output: Contribution to journalArticle (Academic Journal)

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Abstract

Background: Incontinence has a greater detrimental effect on quality of life than other symptoms of overactive bladder (OAB) and is often difficult to treat with antimuscarinic mono therapy.

Objective: To evaluate efficacy, safety/tolerability of combination (solifenacin5 mg/mirabegron 50 mg) vs solifenacin 5 or 10 mg in OAB patients remaining incontinent after 4-wk solifenacin 5 mg.

Design, Setting, and Participants: OAB patients remaining incontinent despitedaily solifenacin 5 mg during 4-wk single-blind run-in, were randomised 1:1:1 to double-blind daily combination, solifenacin 5 or 10 mg for 12 wk. Patients receiving combination were initiated on mirabegron 25 mg increasing to 50 mg after week 4.

Outcome Measurements and Statistical Analysis: Primary endpoint: change from baseline to end of treatment (EOT) in mean number of incontinence episodes/24 (stratified rank ANCOVA). Key secondary endpoints: change from baseline to EOT in mean number of micturitions/24 h (ANCOVA) and number of incontinence episodes during 3-d diary at EOT (mixed effects Poisson regression). BESIDE tested the superiority of combination vs solifenacin 5 mg, noninferiority (and potential superiority) of combination vs solifenacin 10 mg (key secondary endpoints), and safety/tolerability of combination vs Solifenacin monotherapy.

Results and Limitations: 2174 patients were randomised: combination (n=727), solifenacin 5mg (n=728) or 10 mg (n=719). At EOT, combination was superior to solifenacin 5 mg, with significant improvements in daily incontinence (p=0.001), daily micturitions (p<0.001) and incontinence during 3-d diary (p=0.014). Combination was noninferior to BESIDE Primary Final resubmission draft January 2016 4 solifenacin 10 mg for key secondary endpoints, and superior vs solifenacin 10 mg for improving daily micturitions. All treatments were well tolerated.

Conclusions: Adding mirabegron 50 mg to solifenacin 5 mg further improved OAB symptoms vs solifenacin 5 or 10 mg, and was well tolerated in OAB patients remaining incontinent after initial solifenacin 5 mg
Original languageEnglish
Pages (from-to)136-145
Number of pages10
JournalEuropean Urology
Volume70
Issue number1
Early online date8 Mar 2016
DOIs
Publication statusPublished - Jul 2016

Structured keywords

  • Centre for Surgical Research

Keywords

  • Add-on therapy
  • Incontinence
  • Mirabegron
  • Overactive bladder
  • Solifenacin

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