Phase III, randomised, double-blind, placebo-controlled study of the β3-adrenoceptor agonist mirabegron, 50 mg once daily, in Japanese patients with overactive bladder

BJU Int. 2014 Jun;113(6):951-60. doi: 10.1111/bju.12649. Epub 2014 Mar 17.

Abstract

Objective: To evaluate the efficacy and safety of the β3-adrenoceptor agonist mirabegron, in a Japanese population with overactive bladder (OAB).

Patients and methods: This randomised, double-blind, placebo-controlled phase III study enrolled adult patients experiencing OAB symptoms for ≥24 weeks. Patients with ≥ 8 micturitions/24 h and ≥1 urgency episode/24 h or ≥1 urgency incontinence episode/24 h were randomised to once-daily placebo, mirabegron 50 mg or tolterodine 4 mg (as an active comparator, without testing for non-inferiority of efficacy and safety) for 12 weeks. The primary endpoint was the change in the mean number of micturitions/24 h from baseline to final assessment. Secondary endpoints included micturition variables related to urgency and/or incontinence and quality-of-life domain scores on the King's Health Questionnaire. Safety assessments included adverse events (AEs), post-void residual urine volume, laboratory variables, vital signs and 12-lead electrocardiogram.

Results: A total of 1139 patients were randomised to receive placebo (n = 381), mirabegron 50 mg (n = 380) or tolterodine 4 mg (n = 378). Demographic and baseline characteristics were similar among the treatment groups. At final assessment, mirabegron was significantly superior to placebo in terms of mean [sd] change from baseline in number of micturitions/24 h (-1.67 [2.212] vs -0.86 [2.354]; P < 0.001) and mean [sd] change from baseline in number of urgency episodes/24 h (-1.85 [2.555] vs -1.37 [3.191]; P = 0.025), incontinence episodes/24 h (-1.12 [1.475] vs -0.66 [1.861]; P = 0.003), urgency incontinence episodes/24 h (-1.01 [1.338] vs -0.60 [1.745]; P = 0.008), and volume voided/micturition (24.300 [35.4767] vs 9.715 [29.0864] mL; P < 0.001). The incidence of AEs in the mirabegron group was similar to that in the placebo group. Most AEs were mild and none were severe.

Conclusions: Mirabegron 50 mg once daily is an effective treatment for OAB symptoms, with a low occurrence of side effects in a Japanese population.

Keywords: efficacy; mirabegron; overactive bladder; safety; β3-adrenoceptor agonist.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetanilides / administration & dosage*
  • Adrenergic beta-3 Receptor Agonists / administration & dosage*
  • Aged
  • Asian Continental Ancestry Group
  • Benzhydryl Compounds / administration & dosage
  • Cresols / administration & dosage
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Muscarinic Antagonists / administration & dosage
  • Phenylpropanolamine / administration & dosage
  • Thiazoles / administration & dosage*
  • Tolterodine Tartrate
  • Urinary Bladder, Overactive / drug therapy*

Substances

  • Acetanilides
  • Adrenergic beta-3 Receptor Agonists
  • Benzhydryl Compounds
  • Cresols
  • Muscarinic Antagonists
  • Thiazoles
  • Phenylpropanolamine
  • Tolterodine Tartrate
  • mirabegron