Safety and Tolerability Results from the PILLAR Study: A Phase IV, Double-Blind, Randomized, Placebo-Controlled Study of Mirabegron in Patients ≥ 65 years with Overactive Bladder-Wet

Abstract

Background In older patients with overactive bladder (OAB), mirabegron, a β 3-adrenoreceptor agonist, represents an alternative treatment that may have a favorable risk-benefit profile. Objectives Our objective was to further examine the safety and tolerability of mirabegron versus placebo treatment in patients aged ≥ 65 years with OAB-wet. Methods We conducted a 12-week, double-blind, randomized, placebo-controlled phase IV study to compare mirabegron with placebo. Community-dwelling patients aged ≥ 65 years with OAB-wet (one or more incontinence episode and three or more urgency episodes, and an average of eight or more micturitions/24 h over a 3-day diary) were randomized to receive placebo or mirabegron 25 mg/day (optional dose escalation to 50 mg/day at week 4 or 8). Safety analyses were performed for adverse events (AEs) and vital signs on all randomized patients who received one or more dose of study drug. Results Treatment-emergent AEs (TEAEs), the majority mild or moderate in severity, were reported in 39.4% of placebo patients and 44.2 and 49.8% of those who received mirabegron 25 mg or 50 mg, respectively. The most common TEAEs in mirabegron-treated patients were urinary tract infection, headache, and diarrhea. The incidence of TEAEs was slightly higher in mirabegron patients aged ≥ 75 years than in those aged < 75 years. There were no clinically meaningful differences in changes in vital signs from baseline to end of treatment for any treatment group, and no differences were observed between mirabegron and placebo treatment groups. TEAEs tended to occur early post exposure and were not dose related. Conclusions Mirabegron treatment was well-tolerated in older adults with OAB-wet. Safety and tolerability were consistent with the known mirabegron safety profile. Trial Registration This study is registered at ClinicalTrials.gov: NCT02216214.

Clinical Utility of β3-Adrenoreceptor Agonists for the Treatment of Overactive Bladder: A Review of the Evidence and Current Recommendations

“…The efficacy of mirabegron in patients aged >65 years was assessed in a large double-blind, randomized, placebo-controlled, multicenter study that enrolled 888 subjects with OAB wet in the US and Canada.After 12 weeks of treatment, the authors found significant superiority of mirabegron over placebo with respect to reduction in frequency, number of urgency and incontinence episodes, and mean voided volume. 43 These findings are consistent with those published previously, which reported a pooled analysis of patients aged >65 years enrolled in three phase III studies. 44 These data were also supported by work of Lozano-Ortega et al who proved that mirabegron was similarly as effective as ACh across all efficacy end points in an older population.…”

Mirabegron in the Management of Overactive Bladder Syndrome

“…An in-depth examination of the safety and tolerability of mirabegron among the participants in the PILLAR study demonstrated a frequency of TEAEs (47%) similar to that of previously reported phase III studies enrolling patients aged >65 years. 57 Those TEAEs most frequently reported (UTI, headache, and diarrhoea) were in line with the known mirabegron safety profile, and did not appear to be either age, or dose dependent. Furthermore, a pre-planned analysis aimed to detect potential cognitive decline related to treatment with mirabegron, using a rapid screening instrument for mild cognitive impairment, the Montreal Cognitive Assessment (MoCA), was conducted as part of the PILLAR study.…”

Repurposing beta-3 adrenergic receptor agonists for Alzheimer’s disease: beneficial effects in a mouse model

“…This class of drugs is actively being tested in clinical studies for metabolic diseases [ 109 , 110 ] and CL-316,243 has been previously investigated in humans as well [ 111 ]. As an example, mirabegron (Myrbetriq®) has been approved by the Food and Drug Administration for the treatment of overactive bladder [ 41 , 112 ], and large randomized controlled trials have confirmed its safety and tolerability profiles [ 113 ], even in the elderly population [ 114 ]. Thus, the potential translation to clinical use of this class of drugs in AD is high.…”