title: Efficacy and tolerability of mirabegron, a β(3)-adrenoceptor agonist, in patients with overactive bladder: results from a randomised European-Australian phase 3 trial.
abstract: BACKGROUND
  Mirabegron, a β(3)-adrenoceptor agonist, has been developed for the treatment of overactive bladder (OAB).
  
  
  OBJECTIVE
  To assess the efficacy and tolerability of mirabegron versus placebo.
  
  
  METHODS
  Multicenter randomised double-blind, parallel-group placebo- and tolterodine-controlled phase 3 trial conducted in 27 countries in Europe and Australia in patients ≥ 18 yr of age with symptoms of OAB for ≥ 3 mo.
  
  
  METHODS
  After a 2-wk single-blind placebo run-in period, patients were randomised to receive placebo, mirabegron 50mg, mirabegron 100mg, or tolterodine extended release 4 mg orally once daily for 12 wk.
  
  
  METHODS
  Patients completed a micturition diary and quality-of-life (QoL) assessments. Co-primary efficacy end points were change from baseline to final visit in the mean number of incontinence episodes and micturitions per 24h. The primary comparison was between mirabegron and placebo with a secondary comparison between tolterodine and placebo. Safety parameters included adverse events (AEs), laboratory assessments, vital signs, electrocardiograms, and postvoid residual volume.
  
  
  CONCLUSIONS
  A total of 1978 patients were randomised and received the study drug. Mirabegron 50-mg and 100-mg groups demonstrated statistically significant improvements (adjusted mean change from baseline [95% confidence intervals]) at the final visit in the number of incontinence episodes per 24h (-1.57 [-1.79 to -1.35] and -1.46 [-1.68 to -1.23], respectively, vs placebo -1.17 [-1.39 to -0.95]) and number of micturitions per 24h (-1.93 [-2.15 to -1.72] and -1.77 [-1.99 to -1.56], respectively, vs placebo -1.34 [-1.55 to -1.12]; p<0.05 for all comparisons). Statistically significant improvements were also observed in other key efficacy end points and QoL outcomes. The incidence of treatment-emergent AEs was similar across treatment groups. The main limitation of this study was the short (12-wk) duration of treatment.
  
  
  CONCLUSIONS
  Mirabegron represents a new class of treatment for OAB with proven efficacy and good tolerability. TRIAL IDENTIFICATION: This study is registered at ClinicalTrials.gov, identifier NCT00689104.
authors.affiliation: St. Mary's Hospital, Imperial College, London, UK. vik.khullar@imperial.ac.uk
authors.forename: Vik
authors.initials: V
authors.lastname: Khullar
authors.forename: Gerard
authors.initials: G
authors.lastname: Amarenco
authors.forename: Javier C
authors.initials: JC
authors.lastname: Angulo
authors.forename: Javier
authors.initials: J
authors.lastname: Cambronero
authors.forename: Kjetil
authors.initials: K
authors.lastname: Høye
authors.forename: Ian
authors.initials: I
authors.lastname: Milsom
authors.forename: Piotr
authors.initials: P
authors.lastname: Radziszewski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Rechberger
authors.forename: Peter
authors.initials: P
authors.lastname: Boerrigter
authors.forename: Ted
authors.initials: T
authors.lastname: Drogendijk
authors.forename: Marianne
authors.initials: M
authors.lastname: Wooning
authors.forename: Christopher
authors.initials: C
authors.lastname: Chapple
mesh_terms: D000083:Acetanilides / Q000627:therapeutic use*; D058667:Adrenergic beta-3 Receptor Agonists / Q000627:therapeutic use*; D000368:Aged; D001315:Australia; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D003408:Cresols / Q000627:therapeutic use*; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000627:therapeutic use*; D010665:Phenylpropanolamine / Q000627:therapeutic use*; D011788:Quality of Life; D016037:Single-Blind Method; D011795:Surveys and Questionnaires; D013844:Thiazoles / Q000627:therapeutic use*; D000068737:Tolterodine Tartrate; D016896:Treatment Outcome; D053201:Urinary Bladder, Overactive / Q000150:complications / Q000188:drug therapy*; D053202:Urinary Incontinence, Urge / Q000188:drug therapy / Q000209:etiology; D014554:Urination / Q000187:drug effects
chemical_list: D000083:Acetanilides; D058667:Adrenergic beta-3 Receptor Agonists; D001559:Benzhydryl Compounds; D003408:Cresols; D003692:Delayed-Action Preparations; D018727:Muscarinic Antagonists; D013844:Thiazoles; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate; C520025:mirabegron