Efficacy, safety, and tolerability of mirabegron in patients aged ≥65 yr with overactive bladder wet: a phase IV, double-blind, randomised, placebo-controlled study (PILLAR)

Wagg, Adrian; Staskin, David R.; Engel, Eli; Herschorn, Sender; Kristy, Rita M.; Schermer, Carol R.

doi:10.1016/j.eururo.2019.10.002

Cited by 57 publications

(53 citation statements)

References 27 publications

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“…The primary paper was published recently and includes detailed methods for the study [19]. 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 1:1 to receive placebo or mirabegron.…”

Section: Patientsmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Patientsmentioning

confidence: 99%

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

et al. 2020

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“…Alternatively, mirabegron could be used as a treatment in this population. A phase IV study found that mirabegron improved symptoms of OAB in the elderly, with safety and tolerability consistent with known mirabegron safety profile 14 . A subanalysis of the BESIDE study in those aged over 65 years, which investigated the combination of solifenacin and mirabegron, found no difference between solifenacin 5 mg plus mirabegron 50 mg compared to solifenacin 10 mg 15 .…”

Section: Anticholinergic Loadmentioning

confidence: 56%

Recent advances in managing overactive bladder

et al. 2020

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Overactive bladder syndrome (OAB) is defined as urinary urgency, usually accompanied by frequency and nocturia, with or without urgency incontinence, in the absence of urinary tract infection or other obvious pathology. In this review, we focus on recent advances in the management of OAB. We examine the evidence on the effect of anticholinergic load on OAB patients. Advances in medical treatment include a new beta-3 agonist, vibegron, which is thought to have fewer drug interactions than mirabegron. Treatment of genitourinary syndrome of the menopause with oestrogens and ospemifene have also shown promise for OAB. Botulinum toxin has been shown to be an effective treatment option. We discuss the new implantable neuromodulators that are on the market as well as selective bladder denervation and laser technology.

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“…Full methods are described in the PILLAR primary paper [24], but, in brief, PILLAR was a phase 4, multicentre, 12week study in the US and Canada. Independent Ethics Committee/Institutional Review Board-approved written informed consent was obtained from all participants or their legally authorized representatives.…”

Section: Methodsmentioning

confidence: 99%

“…Mirabegron is a β 3 -adrenoreceptor agonist that represents an alternative OAB treatment to antimuscarinics, and potentially has a more favorable benefit-to-risk ratio in older patient populations [20][21][22][23]. The PILLAR study compared flexibly-dosed mirabegron versus placebo in community-dwelling elderly patients ≥65 years with OAB and incontinence [24]. Statistically significant mean improvements in bladder diary parameters were observed for mirabegron versus placebo, and safety and tolerability were in line with the mirabegron safety profile.…”

Section: Introductionmentioning

confidence: 99%

Effect of mirabegron on cognitive function in elderly patients with overactive bladder: MoCA results from a phase 4 randomized, placebo-controlled study (PILLAR)

et al. 2020

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Background: Antimuscarinics are often used for treatment of overactive bladder (OAB), but exposure to medications such as antimuscarinics that have anticholinergic properties has been linked to adverse cognitive effects. A phase 4 placebocontrolled study (PILLAR; NCT02216214) described the efficacy and safety of mirabegron, a β 3 -adrenoreceptor agonist, for treatment of wet OAB in patients aged ≥65 years. This pre-planned analysis aimed to measure differences in cognitive function between mirabegron and placebo, using a rapid screening instrument for mild cognitive impairment: the Montreal Cognitive Assessment (MoCA).Methods: Outpatients aged ≥65 years with wet OAB were randomized 1:1 to mirabegron or placebo, stratified by age (<75/≥75 years). There were no exclusion criteria regarding cognitive status. Patients randomized to mirabegron initially received 25 mg/day with an optional increase to 50 mg/day after week 4/8 based on patient/investigator discretion. The MoCA was administered at baseline and end of treatment (EoT, week 12). The study protocol was Independent Ethics Committee/Institutional Review Board-approved.Results: Of the 887 randomized patients who received ≥1 dose of study drug, 72.3% were female, 79.5% were white, and 28.1% were aged ≥75 years. All patients had ≥1 comorbidity and 94.3% were receiving ≥1 concomitant medication. One third of patients had a history of psychiatric disorders, the most common being depression (17.2%), insomnia (15.7%), and anxiety (11.4%). Baseline mean (standard error, SE) MoCA total scores were 26.9 (0.1) and 26.8 (0.1) in the mirabegron and placebo groups, respectively. Among patients with MoCA data available at baseline/EoT, 27.1% (115/425) and 25.8% (106/411) of mirabegron and placebo group patients, respectively, had impaired cognitive function at baseline (MoCA total score <26). There was no statistically significant change in adjusted mean (SE) MoCA total score from baseline to EoT in the mirabegron group (−0.2 [0.1]) or the placebo group (−0.1 [0.1]).Conclusions: Treatment with mirabegron for 12 weeks did not contribute to drug-related cognitive side effects in patients aged ≥65 years, as measured by the MoCA. Furthermore, the pattern of change in cognition over time in an older OAB trial population does not appear to differ from that of subjects receiving placebo.

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Efficacy, safety, and tolerability of mirabegron in patients aged ≥65 yr with overactive bladder wet: a phase IV, double-blind, randomised, placebo-controlled study (PILLAR)

Cited by 57 publications

References 27 publications

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

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

Recent advances in managing overactive bladder

Effect of mirabegron on cognitive function in elderly patients with overactive bladder: MoCA results from a phase 4 randomized, placebo-controlled study (PILLAR)

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