title: A phase II dose-ranging study of mirabegron in patients with overactive bladder.
abstract: OBJECTIVE
  Mirabegron is a potent and selective β3-adrenoceptor agonist that may represent an alternative treatment option in place of antimuscarinics for patients with overactive bladder.
  
  
  METHODS
  Patients completed a single-blinded, 2-week placebo run-in period followed by 12 weeks of randomized (n = 928) double-blinded treatment with mirabegron oral controlled absorption system (OCAS) 25, 50, 100, or 200 mg once-daily (QD), placebo or tolterodine extended release (ER) 4 mg QD. The primary endpoint was change from baseline to end-of-treatment in mean number of micturition episodes/24 h. Secondary endpoints included changes in mean volume voided per micturition; mean number of urinary incontinence, urgency urinary incontinence, and urgency episodes/24 h; severity of urgency; nocturia; and quality of life measures. Safety parameters included vital signs, adverse events, laboratory tests, electrocardiogram measurements and post-void residual volume.
  
  
  RESULTS
  Mirabegron 25, 50, 100, and 200 mg resulted in dose-dependent reductions (improvements) from baseline to end-of-treatment in micturition frequency of 1.9, 2.1, 2.1, and 2.2 micturitions/24 h respectively, versus 1.4 micturitions/24 h with placebo (p ≤ 0.05 for the mirabegron 50-, 100-, and 200-mg comparisons). There was a statistically significant improvement with mirabegron compared with placebo for most secondary endpoints including quality of life variables. While there was a significant (p < 0.05) increase from baseline in pulse rate in the mirabegron 100-mg and 200-mg groups, this was not associated with an increased incidence of cardiovascular adverse events.
  
  
  CONCLUSIONS
  The favorable efficacy and tolerability of mirabegron in this phase II dose-finding study has led to its successful advancement into a phase III clinical development program.
authors.affiliation: Department of Urology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Glossop Road, Sheffield, S10 2JF, UK. c.r.chapple@shef.ac.uk
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Chapple
authors.forename: Vladimir
authors.initials: V
authors.lastname: Dvorak
authors.forename: Pjotr
authors.initials: P
authors.lastname: Radziszewski
authors.forename: Philip
authors.initials: P
authors.lastname: Van Kerrebroeck
authors.forename: Jean Jacques
authors.initials: JJ
authors.lastname: Wyndaele
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bosman
authors.forename: Peter
authors.initials: P
authors.lastname: Boerrigter
authors.forename: Ted
authors.initials: T
authors.lastname: Drogendijk
authors.forename: Arwin
authors.initials: A
authors.lastname: Ridder
authors.forename: Ingrid
authors.initials: I
authors.lastname: Van Der Putten-Slob
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamaguchi
mesh_terms: D000083:Acetanilides / Q000009:adverse effects* / Q000627:therapeutic use*; D058667:Adrenergic beta-3 Receptor Agonists / Q000009:adverse effects* / Q000627:therapeutic use*; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D015994:Incidence; D038622:Internationality; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D016037:Single-Blind Method; D013844:Thiazoles / Q000009:adverse effects* / Q000627:therapeutic use*; D016896:Treatment Outcome; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*; D014549:Urinary Incontinence / Q000453:epidemiology
chemical_list: D000083:Acetanilides; D058667:Adrenergic beta-3 Receptor Agonists; D013844:Thiazoles; C520025:mirabegron