title: Randomized double-blind, active-controlled phase 3 study to assess 12-month safety and efficacy of mirabegron, a β(3)-adrenoceptor agonist, in overactive bladder.
abstract: BACKGROUND
  Despite several antimuscarinic treatment options for overactive bladder (OAB), there is still a need for distinct treatment approaches to manage this condition. Mirabegron, a β(3)-adrenoceptor agonist, has demonstrated efficacy and tolerability for up to 12 wk in phase 3 trials.
  
  
  OBJECTIVE
  To assess the 12-mo safety and efficacy of mirabegron.
  
  
  METHODS
  Patients ≥ 18 yr of age with OAB symptoms for ≥ 3 mo.
  
  
  METHODS
  After a 2-wk single-blind placebo run-in, patients with eight or more micturitions per 24h and three or more urgency episodes in a 3-d micturition diary were randomized 1:1:1 to once-daily mirabegron 50mg, mirabegron 100mg, or tolterodine extended release (ER) 4 mg for 12 mo.
  
  
  METHODS
  Primary variable: incidence and severity of treatment-emergent AEs (TEAEs). Secondary variables: change from baseline at months 1, 3, 6, 9, and 12 in key OAB symptoms.
  
  
  CONCLUSIONS
  A total of 812, 820, and 812 patients received mirabegron 50mg, mirabegron 100mg, and tolterodine ER 4 mg, respectively. Baseline demographic and OAB characteristics were similar across groups. TEAEs were reported in 59.7%, 61.3%, and 62.6% of patients, respectively; most were mild or moderate. Serious TEAEs were reported in 5.2%, 6.2%, and 5.4% of patients, respectively. The most common TEAEs were similar across groups. Dry mouth was reported by 2.8%, 2.3%, and 8.6% of patients, respectively. Adjusted mean changes from baseline to final visit in morning systolic blood pressure were 0.2, 0.4, and -0.5mm Hg for mirabegron 50mg, 100mg, and tolterodine ER 4 mg, respectively. Mirabegron and the active control, tolterodine, improved key OAB symptoms from the first measured time point of 4 wk, and efficacy was maintained throughout the 12-mo treatment period. The study was not placebo controlled, which was a limitation.
  
  
  CONCLUSIONS
  The safety and tolerability of mirabegron was established over 1 yr, with sustained efficacy observed over this treatment period.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00688688.
authors.affiliation: Royal Hallamshire Hospital, Sheffield, UK. c.r.chapple@shef.ac.uk
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Chapple
authors.forename: Steven A
authors.initials: SA
authors.lastname: Kaplan
authors.forename: David
authors.initials: D
authors.lastname: Mitcheson
authors.forename: Jiri
authors.initials: J
authors.lastname: Klecka
authors.forename: Jana
authors.initials: J
authors.lastname: Cummings
authors.forename: Ted
authors.initials: T
authors.lastname: Drogendijk
authors.forename: Caroline
authors.initials: C
authors.lastname: Dorrepaal
authors.forename: Nancy
authors.initials: N
authors.lastname: Martin
mesh_terms: D000083:Acetanilides / Q000627:therapeutic use*; D058667:Adrenergic beta-3 Receptor Agonists / Q000627:therapeutic use*; D000368:Aged; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D003248:Constipation / Q000139:chemically induced; D003408:Cresols / Q000627:therapeutic use*; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000627:therapeutic use*; D010665:Phenylpropanolamine / Q000627:therapeutic use*; D016037:Single-Blind Method; 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; D016055:Urinary Retention / Q000139:chemically induced; D014987:Xerostomia / Q000139:chemically induced
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