title: 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).
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Combining mirabegron 25/50 mg and solifenacin 5/10 mg improves objective and subjective efficacy outcomes compared with placebo or solifenacin 5 mg.
authors: Bristol Urological Institute, Southmead Hospital, BS10 5NB, Bristol, UK. paul.abrams@bui.ac.uk.
authors: P
authors: P
authors: Abrams
authors: Guy's and St Thomas' Hospitals, London, UK.
authors: C
authors: C
authors: Kelleher
authors: Tufts University School of Medicine, Boston, MA, USA.
authors: D
authors: D
authors: Staskin
authors: RK Statistics Ltd, Bakewell, UK.
authors: R
authors: R
authors: Kay
authors: Department of Obstetrics and Gynaecology, 1st Medical Faculty, Charles University and General University Hospital, Prague, Czech Republic.
authors: A
authors: A
authors: Martan
authors: Faculty of Healthcare of the University of Prešov, Prešov, Slovakia.
authors: I
authors: I
authors: Mincik
authors: Astellas Pharma BV, Leiden, The Netherlands.
authors: D
authors: D
authors: Newgreen
authors: Astellas Pharma BV, Leiden, The Netherlands.
authors: A
authors: A
authors: Ridder
authors: Astellas Pharma BV, Leiden, The Netherlands.
authors: A
authors: A
authors: Paireddy
authors: Astellas Pharma BV, Leiden, The Netherlands.
authors: R
authors: R
authors: van Maanen
mesh_terms: D000083:Acetanilides / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006304:Health Status; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071081:Minimal Clinically Important Difference; D000071066:Patient Reported Outcome Measures; D011788:Quality of Life; D000069464:Solifenacin Succinate / Q000008:administration & dosage*; D013844:Thiazoles / Q000008:administration & dosage*; D016896:Treatment Outcome; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*; D064804:Urological Agents / Q000008:administration & dosage*
chemical_list: D000083:Acetanilides; D013844:Thiazoles; D064804:Urological Agents; D000069464:Solifenacin Succinate; C520025:mirabegron
keywords: Combination therapy; Mirabegron; Patient-reported outcomes; Responder analyses; SYMPHONY; Solifenacin