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

Abstract

Registered at clinicaltrials.gov (NCT00966004). 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] Conclusions• Mirabegron 50 mg once daily is an effective treatment for OAB symptoms, with a low occurrence of side effects in a Japanese population.

Overactive bladder: pharmacological treatment

“…Mirabegron is the first β3 agonist to be used in clinical practice. [50][51][52][53] (D) To assess the efficacy and tolerability of this drug therapy in the treatment of idiopathic overactive bladder (IOAB), two phase II 54,55 (B) and six phase III [56][57][58][59][60][61] (A) randomized clinical trials (RCTs) recruited more than 10,500 adult patients. Of these, seven were randomized, double-blind and placebo-controlled with follow-up of four (one study) and 12 (six studies) weeks, and one was non-placebo-controlled (vs. tolterodine) with 12-month follow-up.…”

Practical points in the medical treatment of overactive bladder and nocturia in the elderly

“…Recent Phase III trials have confirmed the efficacy and safety of mirabegron in treatment of OAB [6970717273]. A urodynamic study in men with OAB and BOO revealed that mirabegron did not adversely affect the maximum flow rate (Qm ax ) and detrusor pressure at Q max after 12 weeks of treatment [74].…”

Physiology and relevance of human adaptive thermogenesis response

“…First-generation b3AR agonists were inadequately selective, and the second generation, although more selective, demonstrated poor oral bioavailability and pharmacokinetics [63]. Mirabegron, a drug that induces smooth muscle relaxation, is the only b3AR compound that has advanced to phase III clinical trials, but only for the treatment of overactive bladder [64,65]; effects on weight have not been assessed, and weight loss has not been reported as adverse event, although it has been recently reported that mirabegron induced BAT activation and increased EE [66].…”