Phase 3
N=91
Open-label Phase 3 Study With Mirabegron in Children From 3 to Less Than 18 Years of Age With Neurogenic Detrusor Overactivity
Neurogenic Detrusor Overactivity
Bottom Line
View on ClinicalTrials.gov: NCT02751931 ↗Enrolled (actual)
91
Serious AEs
16.3%
Results posted
May 2020
Primary outcome: Primary: Change From Baseline in Maximum Cystometric Capacity (MCC) at Week 24 — 72.09; 113.21 mL — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Mirabegron (Drug)
- Age
- Pediatric · 3+ yrs
- Sex
- All
- Sponsor
- Astellas Pharma Europe B.V.
- Primary completion
- Nov 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Maximum Cystometric Capacity (MCC) at Week 24 |
72.09; 113.21 | <0.001 sig |
| SECONDARY Change From Baseline in Bladder Compliance (ΔV/ΔP) |
-4.09; 15.16; 14.62; 13.59 | 0.618 |
| SECONDARY Change From Baseline in Maximum Cystometric Capacity at Week 4 |
41.36; 80.78 | <0.001 sig |
| SECONDARY Change From Baseline in Number of Overactive Detrusor Contractions (> 15 cm H20) Until End of Filling |
0.44; -0.64; -1.86; -0.77 | 0.632 |
| SECONDARY Change From Baseline in Detrusor Pressure at End of Filling |
-12.38; -6.48; -18.11; -13.19 | <0.001 sig |
| SECONDARY Change From Baseline in Filling Bladder Volume Until First Overactive Detrusor Contraction (> 15 cm H20) |
54.00; 41.15; 68.00; 62.00 | <0.001 sig |
| SECONDARY Change From Baseline in Filling Bladder Volume Until First Overactive Detrusor Contraction (> 15 cm H20): Wilcoxon Signed-rank Test Updated Analysis |
48.00; 46.30; 76.00; 78.45 | <0.001 sig |
| SECONDARY Change From Baseline in Filling Bladder Volume Until First Overactive Detrusor Contraction (> 15 cm H20): Paired T-test |
56.09; 73.80; 93.09; 121.33 | <0.001 sig |
| SECONDARY Change From Baseline in Average Catheterized Volume Per Catheterization |
14.58; 35.99; 30.08; 51.96; 36.90; 45.10 | 0.035 sig |
| SECONDARY Change From Baseline in Maximum Catheterized Volume |
17.50; 42.38; 46.69; 73.25; 45.27; 42.86 | 0.126 |
| SECONDARY Change From Baseline in Maximum Catheterized Daytime Volume (MCDV) |
18.13; 35.58; 37.71; 70.35; 43.91; 38.11 | 0.113 |
| SECONDARY Change From Baseline in Average Morning Catheterized Volume |
7.98; 39.52; 19.81; 75.25; 34.01; 44.43 | 0.617 |
| SECONDARY Change From Baseline in Mean Number of Leakage Episodes Per Day |
0.35; -0.53; -1.14; -0.87; 1.16; -0.65 | 0.818 |
| SECONDARY Change From Baseline in Mean Number of Leakage Episodes Per Day: Updated Analysis |
0.78; -0.71; -1.32; -0.95; 1.68; -0.84 | 0.692 |
| SECONDARY Change From Baseline in Number of Dry Days Per 7 Days (Day and Night Time) |
0.34; 0.82; 0.68; 1.36; 1.14; 2.26 | 0.018 sig |
| SECONDARY Change From Baseline in Pediatric Incontinence Questionnaire (PIN-Q) Score |
2.04; -4.90; 1.30; -6.79 | 0.352 |
| SECONDARY Change From Baseline in Patient Global Impression of Severity Scale (PGI-S) |
0.36; 0.64; 0.42; 0.95 | 0.153 |
| SECONDARY Number of Participants With Clinician Global Impression of Change (CGI-C) |
6; 10; 24; 7; 6; 5 | — |
| SECONDARY Number of Participants With Study Drug Acceptability for Tablets at Week 4 |
0; 0; 0; 0; 5; 7 | — |
| SECONDARY Number of Participants With Study Drug Acceptability for Tablets at Week 24 |
1; 0; 2; 0; 6; 15 | — |
| SECONDARY Number of Participants With Study Drug Acceptability for Tablets at Week 52 |
0; 0; 0; 0; 8; 16 | — |
| SECONDARY Number of Participants With Study Drug Acceptability for Oral Suspension at Week 4 |
1; 0; 3; 0; 4; 2 | — |
| SECONDARY Number of Participants With Study Drug Acceptability for Oral Suspension at Week 24 |
3; 0; 1; 0; 3; 2 | — |
| SECONDARY Number of Participants With Study Drug Acceptability for Oral Suspension at Week 52 |
1; 0; 2; 0; 5; 2 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) |
33; 18; 8; 6; 9; 5 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) of Mirabegron |
9.386; 9.044; 20.55; 18.40 | — |
| SECONDARY Time to Reach Maximum Plasma Concentration of Mirabegron Following Drug Administration (Tmax) |
3.000; 3.500; 3.419; 3.635 | — |
| SECONDARY Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC24) for Mirabegron |
166.3; 137.8; 310.1; 291.6 | — |
| SECONDARY Plasma Concentration of Mirabegron at the End of a Dosing Interval at Steady State (Ctrough) |
5.312; 4.114; 9.024; 8.888 | — |
| SECONDARY Apparent Total Clearance of Mirabegron From Plasma After Oral Administration (CL/F) |
192.5; 202.3; 230.9; 279.6 | — |
| SECONDARY Apparent Volume of Distribution After Non-intravenous Administration (Vz/F) of Mirabegron |
14450; 15380; 12150; 14770 | — |
Summary
The objective of the study was to evaluate the efficacy, safety, tolerability and pharmacokinetics of mirabegron after multiple-dose administration in the pediatric population.
Eligibility Criteria
Inclusion Criteria
- Subject has a body weight of greater than or equal to 11 kg.
- Subject suffers from NDO confirmed by urodynamic investigation at baseline. The diagnosis of NDO must be confirmed by the presence of at least 1 involuntary detrusor contraction > 15 cm H2O from baseline detrusor pressure, and/or a decrease in compliance leading to an increase in baseline detrusor pressure of > 20 cm H2O.
- Subject has been using CIC for at least 4 weeks prior to visit 1/screening.
- Subject has a current indication for drug therapy to manage NDO.
- Subject is able to take the study drug in accordance with the protocol
Exclusion Criteria
- Subject has a known genitourinary condition (other than NDO) that may cause overactive contractions or incontinence or kidney/bladder stones or another persistent urinary tract pathology that may cause symptoms.
- Subject has one of the following gastrointestinal problems: partial or complete obstruction, decreased motility such as paralytic ileus, subjects at risk of gastric retention.
- Subject has a urinary indwelling catheter within 4 weeks prior to visit 1/screening.
- Subject has a surgically treated underactive urethral sphincter
- Subject has vesico-ureteral reflux grade 3 to 5.
- Subject has undergone bladder augmentation surgery.
- Subject receives electrostimulation therapy, if started within 30 days before visit 1/screening or is expected to start during the study period. Subjects who are on an established regimen may remain on this for the duration of the study.
- Subject suffers from a symptomatic urinary tract infection (UTI) at baseline (symptomatic is defined as pain, fever, hematuria, new onset foul-smelling urine). If present at visit 1/screening or diagnosed between visit 1/screening and visit 3/baseline, the UTI should be treated successfully (clinical recovery) prior to baseline. If a symptomatic UTI is present at baseline, all baseline assessments are allowed to be postponed for a maximum of 7 days until the UTI is successfully treated (clinical recovery).
- Subject has a (mean) resting pulse rate > 99th percentile [Fleming et al, 2011].
- Subject has an established hypertension and a systolic or diastolic blood pressure greater than the 99th percentile of the normal range determined by sex, age and height, plus 5mmHg [NIH 2005].
- Subject has a risk of QT prolongation (e.g., hypokalemia, long QT syndrome [LQTS]; or family history of LQTS, exercise-induced syncope).
- Subject has severe renal impairment (eGFR according to Larsson equation 4 months prior to visit 1/screening and the subject experiences symptoms comparable to those existing prior to the botulinum toxin injections.
Data sourced from ClinicalTrials.gov (NCT02751931). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.