Combination treatment with mirabegron and solifenacin in patients with overactive bladder: exploratory responder analyses of efficacy and evaluation of patient-reported outcomes from a randomized, double-blind, factorial, dose-ranging, Phase II study (SYMPHONY)

World J Urol. 2017 May;35(5):827-838. doi: 10.1007/s00345-016-1908-1. Epub 2016 Aug 11.


Purpose: This large dose-ranging study explored the benefits of different combinations of mirabegron and solifenacin on health-related quality of life (HRQoL), based on patient-reported outcomes (PROs), and patients ('responders') achieving clinically meaningful improvements in efficacy and HRQoL.

Methods: SYMPHONY (NCT01340027) was a Phase II, placebo- and monotherapy-controlled, dose-ranging, 12-week trial. Adult patients with overactive bladder (OAB) for ≥3 months were randomized to 1 of 12 groups: 6 combination (solifenacin 2.5/5/10 mg + mirabegron 25/50 mg), 5 monotherapy (solifenacin 2.5/5/10 mg, or mirabegron 25/50 mg), or placebo. Change from baseline to end of treatment was assessed, versus placebo and solifenacin 5 mg in: PROs (OAB-q [Symptom Bother/total HRQoL] and Patient Perception of Bladder Condition score), and responders achieving minimally important differences (MIDs) in PROs and predetermined clinically meaningful improvements in efficacy (e.g. <8 micturitions/24 h). Changes in PROs and responders were analysed using an ANCOVA model and logistic regression, respectively.

Results: The Full Analysis Set included 1278 patients. Combination therapy of solifenacin 5/10 mg + mirabegron 25/50 mg significantly improved PROs versus solifenacin 5 mg and placebo, and significantly more responders achieved MIDs in PROs and efficacy. Micturition frequency normalization was approximately twofold greater with 10 + 25 mg (OR 2.06 [95 % CI 1.11, 3.84; p = 0.023]) and 5 + 50 mg (OR 1.91 [95 % CI 1.14, 3.21; p = 0.015]) versus solifenacin 5 mg.

Conclusion: Combining mirabegron 25/50 mg and solifenacin 5/10 mg improves objective and subjective efficacy outcomes compared with placebo or solifenacin 5 mg.

Keywords: Combination therapy; Mirabegron; Patient-reported outcomes; Responder analyses; SYMPHONY; Solifenacin.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Acetanilides / administration & dosage*
  • Adult
  • Aged
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Health Status
  • Humans
  • Male
  • Middle Aged
  • Minimal Clinically Important Difference
  • Patient Reported Outcome Measures
  • Quality of Life*
  • Solifenacin Succinate / administration & dosage*
  • Thiazoles / administration & dosage*
  • Treatment Outcome
  • Urinary Bladder, Overactive / drug therapy*
  • Urological Agents / administration & dosage*


  • Acetanilides
  • Thiazoles
  • Urological Agents
  • Solifenacin Succinate
  • mirabegron