Introduction and hypothesisMirabegron is a potent and selective β3-adrenoceptor agonist that may represent an alternative treatment option in place of antimuscarinics for patients with overactive bladder.MethodsPatients 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.ResultsMirabegron 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.ConclusionsThe 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.

SUMMA RYAims: To evaluate the safety and tolerability of the b 3 -adrenoceptor agonist, mirabegron, in patients with overactive bladder (OAB). Methods: Tolerability and safety data from three 12-week, randomised, placebo-controlled, double-blind, Phase III trials (Studies 046, 047 and 074) were pooled by treatment group. The three studies were of a similar design, although the assessed doses of mirabegron [25, 50 or 100 mg once daily (qd)] varied, and tolterodine extended release (ER) 4 mg was included as an active-control arm in Study 046 only. Tolerability and safety data from a 1-year, randomised, double-blind, Phase III trial (Study 049) are also presented. Safety variables included the incidence and severity of treatmentemergent adverse events (TEAEs), vital signs and electrocardiogram data. Results: Mirabegron (25, 50 or 100 mg qd) was safe and well-tolerated in patients with OAB over 12-week (n = 2736) and 1-year (n = 1632) periods. The incidence of TEAEs and treatment discontinuations as a result of TEAEs was low; the majority were mild in severity and few were serious. Hypertension, nasopharyngitis and urinary tract infection were the most common TEAEs with mirabegron. The mirabegron tolerability profile was similar to that seen with placebo and tolterodine ER 4 mg, except for dry mouth, which occurred, on average, five times less frequently with mirabegron than tolterodine ER 4 mg. In the pooled 12-week analysis, mirabegron 50 mg was associated with placebo-adjusted mean increases of 0.4-0.6 mmHg in blood pressure and approximately one beat per minute in pulse rate, both reversible upon treatment discontinuation. The incidence of Major Adverse Cardiovascular Events as adjudicated by an independent cardiovascular committee was low and similar across treatment groups. Conclusion: The favourable tolerability profile of mirabegron in patients with OAB may allow improved treatment compliance compared with antimuscarinics, with important implications for patient outcomes. What's knownOral antimuscarinic agents are currently the standard pharmacological treatment for the symptoms of overactive bladder (OAB), but can be associated with suboptimal efficacy and adverse events (AEs) including dry mouth, constipation and blurred vision that limit patient compliance. The b 3 -adrenoceptor agonist, mirabegron, has a different mechanism of action to that of antimuscarinic agents and is the first in this new class of compounds to be approved for the treatment of OAB. What's newA randomised, 1-year, Phase III trial and a pooled analysis of three randomised, 12-week, Phase III trials demonstrate that mirabegron has a favourable tolerability profile in patients with OAB. Hypertension, nasopharyngitis and urinary tract infection were the most common AEs with mirabegron. Except for dry mouth (up to fivefold more frequent with tolterodine extended release (ER) 4 mg than mirabegron), the incidence of AEs was similar for mirabegron, placebo and tolterodine ER 4 mg.

No abstract

No abstract

Transcutaneous electrical stimulation of the urinary bladder in patients with neurogenic bladder dysfunction improves lower urinary tract function. Urodynamic studies executed 2 months after finishing TES show persistent results.