Efficacy and safety of mirabegron in children and adolescents with neurogenic detrusor overactivity: An open-label, phase 3, dose-titration study

Abstract

Aims: To evaluate the efficacy and safety of mirabegron in children and adolescents (aged 3 to <18 years) with neurogenic detrusor overactivity (NDO) using clean intermittent catheterization.

Methods: In this open-label, multicenter, baseline-controlled, Phase III study (NCT02751931), participants received once-daily mirabegron at an adult dose equivalent of 25 mg. Dose was increased to 50 mg equivalent unless there were safety/tolerability concerns. The primary efficacy endpoint was change from baseline to Week 24 in maximum cystometric capacity (MCC). Secondary urodynamic assessments, Pediatric Incontinence Questionnaire (PIN-Q), Patient Global Impression of Severity (PGI-S), Clinician Global Impression of Change (CGI-C), and Acceptability questionnaires were included.

Results: Overall, 86 participants (55 aged 3 to <12 years, 31 aged 12 to <18 years) received treatment; 68 were included in efficacy assessments. A statistically significant increase in MCC from baseline to Week 24 was observed (87.20 ml, 95% confidence interval: 66.07, 108.33; p < .001); this increase was apparent from Week 4. Significant increases in bladder compliance, bladder volume until first detrusor contraction, average volume per catheterization, maximum daytime catheterized volume and number of dry days per week. Significant decreases in detrusor pressure and number of leakage episodes per day were also observed. Significant improvement in PGI-S but not PIN-Q was observed. Most participants reported their condition had either much or very much improved using the CGI-C. Mirabegron was well tolerated in this population with a profile aligned with that in adults.

Conclusions: Mirabegron was effective and well-tolerated in the treatment of pediatric patients with NDO.

Keywords: children; muscarinic antagonists; neurogenic; neurogenic bladder; overactive detrusor; overactive urinary bladder; urinary bladder.

Conflict of interest statement

Cristian Persu and David T Bolong report no relevant conflicts of interest. Małgorzata Baka‐Ostrowska received an investigator's fee for this study. Camilla Tøndel's institution received an investigator's fee for this study. Achim Steup, Nancy Martin and Christopher Lademacher are employees of Astellas.

© 2021 The Authors. Neurourology and Urodynamics Published by Wiley Periodicals LLC.

Figures

Figure 1

Change in maximum cystometric capacity from baseline to Week 24 LOCF (primary endpoint; full analysis set). CI, confidence interval; LOCF, last observation carried forward

Figure 2

Patient‐reported questionnaire endpoints (secondary endpoints; full analysis set)a *p < 0.05. aIn patients with baseline and postbaseline data. PGI‐S, Patient Global Impression of Severity; PIN‐Q. Pediatric Incontinence Questionnaire