Dataset Information

Mirabegron Add-On Therapy to Tamsulosin in Men with Overactive Bladder: Post Hoc Analyses of Efficacy from the MATCH Study.

ABSTRACT:

Introduction

MATCH was a randomized, double-blind, placebo-controlled study enrolling Japanese and Korean men aged???40 years who still had overactive bladder (OAB) symptoms while receiving tamsulosin. After a 4-week single-blind screening period in which patients received placebo and tamsulosin, patients were randomized to mirabegron 50 mg?+?tamsulosin or placebo?+?tamsulosin for 12 weeks (n?=?568). This post hoc analysis investigated the proportion of treatment responders for each treatment group and for subgroups stratified by age based on voiding diaries and patient-reported outcomes (PROs).

Methods

Responders were defined as those achieving normalization or clinically meaningful improvements in efficacy, or clinically important differences in PROs [??10-point improvement in OAB questionnaire (OAB-q) symptom bother or total health-related quality of life (HRQoL) subscales at end of treatment (EoT; minimally important difference [MID]) or OAB symptom score (OABSS) total score decreased by???3 points at EoT [minimally clinically important change (MCIC)]].

Results

At EoT, micturition frequency normalization was achieved by 30.7% of tamsulosin?+?mirabegron patients and 18.6% of tamsulosin?+?placebo patients. Normalization of urgency and incontinence was 19.1% and 60.7% for tamsulosin?+?mirabegron and 18.2% and 60.0% for tamsulosin?+?placebo. Normalization of OAB symptoms based on OABSS was 17.1% for tamsulosin?+?mirabegron and 14.5% for tamsulosin?+?placebo. Higher proportions of patients in the mirabegron add-on group versus the placebo group reported clinically meaningful improvements in micturitions, urgency, and incontinence and in MCIC for OABSS and MID for the OAB-q subscales. Double- and triple-responder findings were as predicted by the results of single-responder analyses. These results were mirrored in the age groups using cut-offs of 65 and 75 years.

Conclusion

Mirabegron therapy added on to tamsulosin resulted in a higher frequency of responders in terms of normalization (e.g., micturition frequency normalization), clinically meaningful improvements in efficacy (e.g.,???50% decrease in urgency), and minimally important changes in PROs (e.g., MCIC in OABSS).

Trial registration

ClinicalTrials.gov identifier, NCT02656173.

SUBMITTER: Kakizaki H

PROVIDER: S-EPMC7854388 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mirabegron Add-On Therapy to Tamsulosin in Men with Overactive Bladder: Post Hoc Analyses of Efficacy from the MATCH Study.

Kakizaki Hidehiro H Lee Kyu-Sung KS Katou Daisuke D Yamamoto Osamu O Sumarsono Budiwan B Uno Satoshi S Yamaguchi Osamu O

Advances in therapy 20201127 1

<h4>Introduction</h4>MATCH was a randomized, double-blind, placebo-controlled study enrolling Japanese and Korean men aged ≥ 40 years who still had overactive bladder (OAB) symptoms while receiving tamsulosin. After a 4-week single-blind screening period in which patients received placebo and tamsulosin, patients were randomized to mirabegron 50 mg + tamsulosin or placebo + tamsulosin for 12 weeks (n = 568). This post hoc analysis investigated the proportion of treatment responders for each trea ...[more]

PMID: 33245533

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Project description:AIMS/OBJECTIVES:In the BESIDE study, combination therapy (antimuscarinic [solifenacin] and ?3 -adrenoceptor agonist [mirabegron]) improved efficacy over solifenacin monotherapy without exacerbating anticholinergic side effects in overactive bladder (OAB) patients; however, a potential synergistic effect on the cardiovascular (CV) system requires investigation. METHODS:OAB patients remaining incontinent despite daily solifenacin 5 mg during 4-week single-blind run-in, were randomised 1:1:1 to double-blind daily combination (solifenacin 5 mg/mirabegron 25 mg, increasing to 50 mg after week 4), solifenacin 5 or 10 mg for 12 weeks. CV safety assessments included frequency of CV-related treatment-emergent adverse events (TEAEs), change from baseline in vital signs (systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse rate) and electrocardiogram (ECG) parameters. RESULTS:The frequency of hypertension, tachycardia and ECG QT prolongation, respectively, was low and comparable across combination (1.1%, 0.3%, 0.1%), solifenacin 5 mg (0.7%, 0.1%, 0.1%), and solifenacin 10 mg groups (0.8%, 0%, 0.1%). Adjusted mean (SE) change from baseline to end of treatment (EoT) in SBP, DBP, and pulse rate with combination (0.07 mm Hg [0.38], -0.35 mm Hg [0.26], 0.47 bpm [0.28]), solifenacin 5 mg (-0.93 mm Hg [0.38], -0.45 mm Hg [0.26], 0.43 bpm [0.28]) and solifenacin 10 mg (-1.28 mm Hg [0.38], -0.48 mm Hg [0.26], 0.27 bpm [0.28]) was generally comparable, with the exception of a mean treatment difference of ~1 mm Hg in SBP between combination and solifenacin monotherapy; SBP was unchanged with combination and decreased with solifenacin monotherapy. Mean changes from baseline to EoT in ECG parameters were generally similar across treatment groups, except for QT interval corrected using Fridericia's formula, which was higher with solifenacin 10 mg (3.30 mseconds) vs. combination (0.49 mseconds) and solifenacin 5 mg (0.77 mseconds). CONCLUSION:The comparable frequency of CV-related TEAEs, changes in vital signs and ECG parameters indicates no synergistic effect on CV safety outcomes when mirabegron and solifenacin are combined.

Project description:Antimuscarinic agents are currently the predominant treatment option for the clinical management of the symptoms of overactive bladder (OAB). However, low rates of persistence with these agents highlight the need for novel, effective and better-tolerated oral pharmacological agents. Mirabegron is a ?3-adrenoceptor agonist developed for the treatment of OAB, with a mechanism of action distinct from that of antimuscarinics. In a randomized, double-blind, placebo- and active-controlled Phase 3 trial conducted in Europe and Australia (NCT00689104), mirabegron 50 mg and 100 mg resulted in statistically significant reductions from baseline to final visit, compared with placebo, in the co-primary end points - mean number of incontinence episodes/24 h and mean number of micturitions/24 h. We conducted a post hoc, subgroup analysis of this study in order to evaluate the efficacy of mirabegron in treatment-naïve patients and patients who had discontinued prior antimuscarinic therapy because of insufficient efficacy or poor tolerability.Patients were randomized to placebo, mirabegron 50 or 100 mg, or tolterodine extended release (ER) 4 mg orally, once-daily, for 12 weeks. For the post hoc analysis, the primary patient population was divided into the following subgroups: (1) patients who had not received any prior antimuscarinic OAB medication (treatment-naïve) and (2) patients who had received prior antimuscarinic OAB medication. The latter subgroup was further subdivided into patients who discontinued due to: (3) insufficient efficacy or (4) poor tolerability. Analysis of the co-primary efficacy endpoints by subgroup was performed using analysis of covariance with treatment group, subgroup, sex, geographical region, and subgroup-by-treatment interaction as fixed factors; and baseline value as a covariate.Mirabegron, 50 mg and 100 mg once-daily, demonstrated similar improvements in the frequency of incontinence episodes and micturitions in OAB patients who were antimuscarinic-naïve and who had discontinued prior antimuscarinic therapy. While mirabegron demonstrated improvements in incontinence and micturition frequency in patients who had discontinued prior antimuscarinic therapy due to insufficient efficacy, the response to tolterodine was similar to that of placebo.In this post hoc subgroup analysis, mirabegron provided treatment benefits in OAB patients who were antimuscarinic treatment-naïve and in patients who had received prior antimuscarinic treatment.

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Dataset Information

Mirabegron Add-On Therapy to Tamsulosin in Men with Overactive Bladder: Post Hoc Analyses of Efficacy from the MATCH Study.

Introduction

Methods

Results

Conclusion

Trial registration

Publications

Mirabegron Add-On Therapy to Tamsulosin in Men with Overactive Bladder: Post Hoc Analyses of Efficacy from the MATCH Study.

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