Mirabegron for the treatment of overactive bladder: a prespecified pooled efficacy analysis and pooled safety analysis of three randomised, double‐blind, placebo‐controlled, phase III studies

Abstract

IntroductionTo examine pooled efficacy data from three, large phase III studies comparing mirabegron (50 and 100 mg) with placebo, and pooled safety data including additional mirabegron 25 mg and tolterodine extended release (ER) 4 mg results.MethodsThis prespecified pooled analysis of three randomised, double-blind, placebo-controlled, 12-week studies, evaluated efficacy and safety of once-daily mirabegron 25 mg (safety analysis), 50 or 100 mg (efficacy and safety analyses) and tolterodine ER 4 mg (safety analysis) for the treatment of symptoms of overactive bladder (OAB). Co-primary efficacy measures were change from baseline to Final Visit in the mean number of incontinence episodes/24 h and mean number of micturitions/24 h. Key secondary efficacy end-points included mean number of urgency episodes/24 h and mean volume voided/micturitions, while other end-points included patient-reported outcomes according to the Treatment Satisfaction-Visual Analogue Scale (TS-VAS) and responder analyses [dry rate (posttreatment), ≥ 50% reduction in incontinence episodes/24 h, ≤ 8 micturitions/24 h (post hoc analysis)]. The safety analysis included adverse event (AE) reporting, laboratory assessments, ECG, postvoid residual volume and vital signs (blood pressure, pulse rate).ResultsMirabegron (50 and 100 mg once daily) demonstrated statistically significant improvements compared with placebo for the co-primary end-points, key secondary efficacy variables, TS-VAS and responder analyses (all comparisons p < 0.05). Mirabegron is well tolerated and demonstrates a good safety profile. The most common AEs (≥ 3%) included hypertension, nasopharyngitis and urinary tract infection (UTI); the incidence of hypertensive events and UTIs decreased with increasing dose. For mirabegron, the incidence of the bothersome antimuscarinic AE, dry mouth, was at placebo level and of a lesser magnitude than tolterodine.ConclusionThe efficacy and safety of mirabegron are demonstrated in this large pooled clinical trial dataset in patients with OAB.

Mirabegron as Add-On Treatment to Solifenacin in Patients with Incontinent Overactive Bladder and an Inadequate Response to Solifenacin Monotherapy

“…Both classes of drugs exhibit similar efficacy, but unlike antimuscarinics, mirabegron is not associated with anticholinergic side effects. [10][11][12] Patients are usually initiated on an antimuscarinic, with dose escalation if symptom improvement is inadequate. This may increase the anticholinergic burden, the risk of bothersome side effects and treatment discontinuation.…”

The overactive bladder: where are we in 2016?

“…13 The mean number of micturition episodes also decreased significantly with mirabegron 50mg compared to placebo, -1.75 versus -1.20 respectively (p<0.05).…”

Cost-effectiveness of mirabegron compared to tolterodine ER 4 mg for overactive bladder in Canada

“…27 In a pre-specified pooled analysis of three 12-week, randomized, placebo-controlled studies (one of which also included a tolterodine ER 4 mg arm), mirabegron (50 mg and 100 mg once-daily) was associated with statistically significant reductions in incontinence episodes, frequency, and urgency compared with placebo. 28 The pooled analysis included an active-controlled study (SCORPIO), designed to compare the efficacy between mirabegron and placebo, as well as tolterodine ER (4 mg once-daily; included as an active control to placebo). The study, showed statistically significant reductions in incontinence episodes and micturition frequency (the co-primary endpoints) for mirabegron vs. placebo, but not for tolterodine ER 4 mg vs. placebo.…”

“…[40][41][42]48 Unit costs per incontin- Symptom severity cutoff points between different levels were roughly based on qui ntiles for each number in pooled data from three pivotal, randomized trials of mirabegron: SCORPIO, 29,31 ARIES, 28 and CAPRICORN. 37 Patient distribution was based on the SCORPIO study.…”

“…This monthly cost of absenteeism was calculated as the percentage of work time missed (using data from the Work Productivity and Activity Impairment questionnaire in SCORPIO) multiplied by Canadian gross monthly earnings 48 and the proportion of patients with OAB of working age. Based on an estimated mean age of 60 years, 28 it was estimated that approximately 34.7% of patients would still be employed.…”