Efficacy and safety of combinations of mirabegron and solifenacin compared with monotherapy and placebo in patients with overactive bladder (SYNERGY study)

• Published in: BJU international 2017-10, Vol.120 (4), p.562-575
• Main Authors: Herschorn, Sender, Chapple, Christopher R., Abrams, Paul, Arlandis, Salvador, Mitcheson, David, Lee, Kyu‐Sung, Ridder, Arwin, Stoelzel, Matthias, Paireddy, Asha, Maanen, Rob, Robinson, Dudley
• Format: Article
• Language: English
• Subjects: Acetanilides - administration & dosage; Acetanilides - adverse effects; Adult; Aged; Clinical trials; Constipation; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Dyspepsia; Female; Follow-Up Studies; Humans; Internationality; Laboratories; Male; Maximum Tolerated Dose; Middle Aged; Multivariate Analysis; Risk Assessment; Single-Blind Method; Solifenacin Succinate - administration & dosage; Solifenacin Succinate - adverse effects; Statistical analysis; Statistics; Thiazoles - administration & dosage; Thiazoles - adverse effects; Time Factors; Treatment Outcome; Urinary bladder; Urinary Bladder, Overactive - diagnosis; Urinary Bladder, Overactive - drug therapy; Urinary incontinence; Urinary Incontinence - prevention & control; Urination; Urine
• ISSN: 1464-4096; 1464-410X
• DOI: 10.1111/bju.13882

Objective To evaluate the potential of solifenacin 5 mg combined with mirabegron 25 or 50 mg to deliver superior efficacy compared with monotherapy, with acceptable tolerability, in the general overactive bladder (OAB) population with urinary incontinence (UI). Patients and Methods After a 4‐week placebo run‐in, patients aged ≥18 years with wet OAB (urgency, urinary frequency and UI) for ≥3 months who recorded on average ≥8 micturitions/24 h, ≥1 urgency episode/24 h, and ≥3 UI episodes over the 7‐day micturition diary, were eligible for randomisation to double‐blind treatment [2:2:1:1:1:1 ratio, solifenacin 5 mg + mirabegron 25 mg (combined S5 + M25 group); solifenacin 5 mg + mirabegron 50 mg (combined S5 + M50 group); solifenacin 5 mg; mirabegron 25 mg; mirabegron 50 mg; or placebo for 12 weeks], and 2‐weeks’ single‐blind, placebo run‐out. Co‐primary efficacy variables were change from baseline to end of treatment (EoT) in the mean number of UI episodes/24 h and micturitions/24 h, assessed using a 7‐day electronic micturition diary. Secondary efficacy variables included change from baseline to EoT in the mean volume voided/micturition, change from baseline at weeks 4, 8, 12 and EoT in mean number of UI episodes/24 h, micturitions/24 h, urgency episodes/24 h, urgency UI (UUI) episodes/24 h and nocturia episodes/24 h; the percentage of patients (responders) achieving zero UI episodes/24 h at EoT in the last 7 days prior to each visit, micturition frequency normalisation (