title: Efficacy and Safety of the Selective β3 -Adrenoceptor Agonist Mirabegron in Japanese Patients with Overactive Bladder: A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of the β3 -adrenoceptor agonist, mirabegron, compared with placebo in Japanese patients with overactive bladder (OAB).
  
  
  METHODS
  Patients with OAB symptoms for ≥24 weeks, ≥8 micturitions/24 h on average, and ≥1 episode of urgency and/or urgency incontinence/24 h were randomized to mirabegron (25, 50 or 100 mg) or placebo for 12 weeks. The primary endpoint was change from baseline to end of study in the mean number of micturitions/24 h. Secondary endpoints included micturition variables related to urgency, incontinence, volume voided, and quality of life based on the King's Health Questionnaire (KHQ). Safety was evaluated based on adverse events (AEs), laboratory findings, vital signs, electrocardiogram, and post-void residual volume.
  
  
  RESULTS
  In total, 842 patients were randomized to placebo (n = 214), mirabegron 25 mg (n = 211), 50 mg (n = 208), or 100 mg (n = 209). The primary endpoint was significantly improved in each mirabegron group compared with placebo (P < 0.001; Williams' multiple comparison test). The maximal efficacy in the primary endpoint was observed at the 50 mg dose. Significant improvements were also observed in incontinence, urgency incontinence, mean volume voided, and 3 of the 9 domains from the KHQ (incontinence impact, physical limitations, and severity measures) at each mirabegron dose. Urgency episodes decreased, and mean volume voided increased, dose-dependently. The incidence of AEs in each mirabegron dose was comparable with placebo.
  
  
  CONCLUSIONS
  Mirabegron demonstrated significant improvements in OAB symptoms compared with placebo and was well tolerated.
authors.affiliation: Division of Bioengineering and LUTD Research, School of Engineering, Nihon University, Koriyama, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamaguchi
authors.affiliation: Department of Human Arts Sciences, University and Graduate School of Human Arts Sciences, Saitama, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Marui
authors.affiliation: Department of Continence Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Igawa
authors.affiliation: Department of Urology, University of Yamanashi, Yamanashi, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takeda
authors.affiliation: Department of Urology, Shinshu University, Matsumoto, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Nishizawa
authors.affiliation: Astellas Pharma Inc, Tokyo, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ikeda
authors.affiliation: Astellas Pharma Inc, Tokyo, Japan.
authors.forename: Sumito
authors.initials: S
authors.lastname: Ohkawa
mesh_terms: D000083:Acetanilides / Q000627:therapeutic use*; D058667:Adrenergic beta-3 Receptor Agonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D013844:Thiazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*
chemical_list: D000083:Acetanilides; D058667:Adrenergic beta-3 Receptor Agonists; D013844:Thiazoles; C520025:mirabegron
keywords: dose-response; efficacy; mirabegron; overactive bladder; safety