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NCT02751931: Crocodile

Open-label Phase 3 Study With Mirabegron in Children From 3 to Less Than 18 Years of Age With Neurogenic Detrusor Overactivity

Completed Phase 3 Results posted Last updated 12 November 2024
What this trial tests

Phase 3 trial testing Mirabegron in Neurogenic Detrusor Overactivity in 91 participants. Completed in 6 May 2019.

Timeline
17 June 2016
Primary endpoint
5 November 2018
6 May 2019

Quick facts

Lead sponsorAstellas Pharma Europe B.V.
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment91
Start date17 June 2016
Primary completion5 November 2018
Estimated completion6 May 2019
Sites32 locations across Jordan, Malaysia, Taiwan, Poland, South Korea, Philippines, Croatia, Denmark

Drugs / interventions tested

Conditions studied

Sponsor

Astellas Pharma Europe B.V. — full company profile →

Who can join

Adults 3 to 17, any sex, with Neurogenic Detrusor Overactivity. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Maximum Cystometric Capacity (MCC) at Week 24 Primary · Baseline and week 24

Change from baseline in MCC was based on filling urodynamics (volume at the end of filling). During urodynamic assessments, the bladder was filled until voiding/leakage began, or until the participant experienced pain or discomfort, or because dangerous high detrusor pressure, or 135% of maximum catheterized volume for age had been reached. A valid urodynamic assessment was confirmed valid by the central reviewers. Missing MCC observations at week 24 were imputed using last observation carried forward (LOCF).

GroupValue95% CI
Children (3 to < 12 Years)72.09± 87.09
Adolescents (12 to < 18 Years)113.21± 82.99
Change From Baseline in Bladder Compliance (ΔV/ΔP) Secondary · Baseline and weeks 4 and 24

Bladder compliance was an indication of the elasticity of the bladder wall and was calculated by dividing the change in volume by the change in detrusor pressure during the filling of the bladder. Change from baseline in bladder compliance (change in volume/change in pressure) was assessed by the independent central reviewers and reported as annotations on the urodynamic trace and in an external database. During urodynamic assessments, the bladder was filled until voiding/leakage began, or until the participant experienced pain or discomfort, or because dangerous high detrusor pressure, or 135

Change at Week 4
GroupValue95% CI
Children (3 to < 12 Years)-4.09± 50.78
Adolescents (12 to < 18 Years)15.16± 22.69
Change at Week 24
GroupValue95% CI
Children (3 to < 12 Years)14.62± 42.09
Adolescents (12 to < 18 Years)13.59± 15.02
Change From Baseline in Maximum Cystometric Capacity at Week 4 Secondary · Baseline and week 4

Change from baseline in MCC was based on filling urodynamics (volume at the end of filling). During urodynamic assessments, the bladder was filled until voiding/leakage began, or until the participant experienced pain or discomfort, or because dangerous high detrusor pressure, or 135% of maximum catheterized volume for age had been reached. A valid urodynamic assessment was confirmed valid by the central reviewers.

GroupValue95% CI
Children (3 to < 12 Years)41.36± 71.64
Adolescents (12 to < 18 Years)80.78± 96.15
Change From Baseline in Number of Overactive Detrusor Contractions (> 15 cm H20) Until End of Filling Secondary · Baseline and weeks 4 and 24

Detrusor overactivity is the occurrence of involuntary detrusor contractions during filling cystometry. During urodynamic assessments, the bladder was filled until voiding/leakage began, or until the participant experienced pain or discomfort, or because dangerous high detrusor pressure, or 135% of maximum catheterized volume for age had been reached. A valid urodynamic assessment was confirmed valid by the central reviewers.

Change at Week 4
GroupValue95% CI
Children (3 to < 12 Years)0.44± 5.82
Adolescents (12 to < 18 Years)-0.64± 2.94
Change at Week 24
GroupValue95% CI
Children (3 to < 12 Years)-1.86± 4.16
Adolescents (12 to < 18 Years)-0.77± 3.87
Change From Baseline in Detrusor Pressure at End of Filling Secondary · Baseline and weeks 4 and 24

Detrusor pressure was defined as bladder pressure minus intra-abdominal pressure as assessed by urodynamics. Filling was stopped (end of filling) when the detrusor pressure exceeded 100 cm H2O or was considered dangerously high by the investigator or urodynamicist (for instance, a prolonged passive detrusor pressure \> 40 cm H2O). During urodynamic assessments, the bladder was filled until voiding/leakage began, or until the participant experienced pain or discomfort, or because dangerous high detrusor pressure, or 135% of maximum catheterized volume for age had been reached. A valid urodynami

Change at Week 4
GroupValue95% CI
Children (3 to < 12 Years)-12.38± 19.56
Adolescents (12 to < 18 Years)-6.48± 30.70
Change at Week 24
GroupValue95% CI
Children (3 to < 12 Years)-18.11± 19.97
Adolescents (12 to < 18 Years)-13.19± 19.91
Change From Baseline in Filling Bladder Volume Until First Overactive Detrusor Contraction (> 15 cm H20) Secondary · Baseline and weeks 4 and 24

Detrusor overactivity is the occurrence of involuntary detrusor contractions during filling cystometry. During urodynamic assessments, the bladder was filled until voiding/leakage began, or until the participant experienced pain or discomfort, or because dangerous high detrusor pressure, or 135% of maximum catheterized volume for age had been reached. A valid urodynamic assessment was confirmed valid by the central reviewers. If no detrusor contraction of \> 15 cm H2O occurred, the bladder volume was imputed with maximum cystometric capacity.

Change at Week 4
GroupValue95% CI
Children (3 to < 12 Years)54.0013.00 – 105.30
Adolescents (12 to < 18 Years)41.153.00 – 62.50
Change at Week 24
GroupValue95% CI
Children (3 to < 12 Years)68.0032.00 – 110.0
Adolescents (12 to < 18 Years)62.004.00 – 95.15
Change From Baseline in Filling Bladder Volume Until First Overactive Detrusor Contraction (> 15 cm H20): Wilcoxon Signed-rank Test Updated Analysis Secondary · Baseline and weeks 4 and 24

Detrusor overactivity is the occurrence of involuntary detrusor contractions during filling cystometry. During urodynamic assessments, the bladder was filled until voiding/leakage began, or until the participant experienced pain or discomfort, or because dangerous high detrusor pressure, or 135% of maximum catheterized volume for age had been reached. A valid urodynamic assessment was confirmed valid by the central reviewers. If no detrusor contraction of \> 15 cm H2O occurred, the bladder volume was imputed with maximum cystometric capacity. This updated analysis is presented as the original

Change at Week 4
GroupValue95% CI
Children (3 to < 12 Years)48.005.00 – 88.00
Adolescents (12 to < 18 Years)46.30-23.90 – 176.00
Change at Week 24
GroupValue95% CI
Children (3 to < 12 Years)76.0032.00 – 147.20
Adolescents (12 to < 18 Years)78.4526.00 – 176.50
Change From Baseline in Filling Bladder Volume Until First Overactive Detrusor Contraction (> 15 cm H20): Paired T-test Secondary · Baseline and weeks 4 and 24

Detrusor overactivity is the occurrence of involuntary detrusor contractions during filling cystometry. During urodynamic assessments, the bladder was filled until voiding/leakage began, or until the participant experienced pain or discomfort, or because dangerous high detrusor pressure, or 135% of maximum catheterized volume for age had been reached. A valid urodynamic assessment was confirmed valid by the central reviewers. If no detrusor contraction of \> 15 cm H2O occurred, the bladder volume was imputed with maximum cystometric capacity.

Change at Week 4
GroupValue95% CI
Children (3 to < 12 Years)56.09± 96.23
Adolescents (12 to < 18 Years)73.80± 117.21
Change at Week 24
GroupValue95% CI
Children (3 to < 12 Years)93.09± 88.14
Adolescents (12 to < 18 Years)121.33± 159.84
Change From Baseline in Average Catheterized Volume Per Catheterization Secondary · Baseline and weeks 2, 4, 8, 12, 24, 36 and 52

For each participant, the average catheterized volume per catheterization was calculated as the sum of all available/non-missing catheterized volumes recorded over 2 measuring days in the weekend diary, whether or not the 2 days were consecutive divided by the number of catheterizations with non-missing volumes. If volumes were recorded on 1 single day of the weekend diary, the average catheterized volume per catheterization was calculated using all available/non-missing catheterized volumes recorded that day. If no volumes were recorded on any day of the weekend diary, the average catheterize

Change at Week 2
GroupValue95% CI
Children (3 to < 12 Years)14.58± 43.98
Adolescents (12 to < 18 Years)35.99± 54.19
Change at Week 4
GroupValue95% CI
Children (3 to < 12 Years)30.08± 49.50
Adolescents (12 to < 18 Years)51.96± 64.71
Change at Week 8
GroupValue95% CI
Children (3 to < 12 Years)36.90± 46.05
Adolescents (12 to < 18 Years)45.10± 53.77
Change at Week 12
GroupValue95% CI
Children (3 to < 12 Years)32.25± 45.51
Adolescents (12 to < 18 Years)43.94± 58.49
Change at Week 24
GroupValue95% CI
Children (3 to < 12 Years)41.63± 58.03
Adolescents (12 to < 18 Years)59.31± 82.22
Change at Week 36
GroupValue95% CI
Children (3 to < 12 Years)53.87± 91.74
Adolescents (12 to < 18 Years)52.14± 74.90
Change at Week 52
GroupValue95% CI
Children (3 to < 12 Years)42.84± 65.31
Adolescents (12 to < 18 Years)42.40± 69.25
Change From Baseline in Maximum Catheterized Volume Secondary · Baseline and weeks 2, 4, 8, 12, 24, 36 and 52

For each participant, the maximum catheterized volume per day was calculated using all available/non-missing catheterized volumes recorded for the 2 measuring days in the weekend e-diary, whether or not these 2 days were consecutive. Maximum value was calculated separately for each measuring day and the mean of the two values was used. If volumes recorded on 1 single day of the weekend e-diary, the maximum catheterized volume per day was calculated using all available/non-zero catheterized volumes recorded that day. If no volumes were recorded on any day of the weekend e-diary, the maximum cat

Change at Week 2
GroupValue95% CI
Children (3 to < 12 Years)17.50± 73.58
Adolescents (12 to < 18 Years)42.38± 78.23
Change at Week 4
GroupValue95% CI
Children (3 to < 12 Years)46.69± 80.29
Adolescents (12 to < 18 Years)73.25± 103.98
Change at Week 8
GroupValue95% CI
Children (3 to < 12 Years)45.27± 75.22
Adolescents (12 to < 18 Years)42.86± 79.97
Change at Week 12
GroupValue95% CI
Children (3 to < 12 Years)33.23± 68.31
Adolescents (12 to < 18 Years)47.29± 69.83
Change at Week 24
GroupValue95% CI
Children (3 to < 12 Years)49.88± 103.70
Adolescents (12 to < 18 Years)84.39± 121.98
Change at Week 36
GroupValue95% CI
Children (3 to < 12 Years)60.09± 121.66
Adolescents (12 to < 18 Years)54.78± 104.54
Change at Week 52
GroupValue95% CI
Children (3 to < 12 Years)53.51± 96.72
Adolescents (12 to < 18 Years)54.30± 104.74
Change From Baseline in Maximum Catheterized Daytime Volume (MCDV) Secondary · Baseline and weeks 2, 4, 8, 12, 24, 36 and 52

For each participant, the MCDV was calculated using all available/non-missing catheterized daytime volumes for the 2 measuring days in the weekend e-diary, whether or not the 2 days were consecutive. Maximum value was calculated separately for each measuring day and the mean of the 2 values was used. If volumes were recorded on 1 single day of the weekend e-diary, the MCDV was calculated using all available/non-zero catheterized daytime volumes recorded that day. If no volumes were recorded on any day of the weekend e-diary, the MCDV was missing. Daytime was defined as the time between wake-up

Change at Week 2
GroupValue95% CI
Children (3 to < 12 Years)18.13± 73.38
Adolescents (12 to < 18 Years)35.58± 86.78
Change at Week 4
GroupValue95% CI
Children (3 to < 12 Years)37.71± 83.33
Adolescents (12 to < 18 Years)70.35± 113.98
Change at Week 8
GroupValue95% CI
Children (3 to < 12 Years)43.91± 74.44
Adolescents (12 to < 18 Years)38.11± 90.88
Change at Week 12
GroupValue95% CI
Children (3 to < 12 Years)29.05± 67.86
Adolescents (12 to < 18 Years)43.04± 73.82
Change at Week 24
GroupValue95% CI
Children (3 to < 12 Years)44.20± 98.31
Adolescents (12 to < 18 Years)81.37± 117.77
Change at Week 36
GroupValue95% CI
Children (3 to < 12 Years)58.49± 121.12
Adolescents (12 to < 18 Years)50.90± 114.05
Change at Week 52
GroupValue95% CI
Children (3 to < 12 Years)53.76± 100.24
Adolescents (12 to < 18 Years)49.13± 117.23
Change From Baseline in Average Morning Catheterized Volume Secondary · Baseline and weeks 2, 4, 8, 12, 24, 36 and 52

The first morning catheterized volume was the first recorded non-zero volume within or after the hour of the wake-up time on a volume-measuring day in the e-diary. The average first morning catheterized volume was calculated as the average of the available first morning catheterized volumes recorded for the 2 measuring days in the weekend e-diary, whether or not these 2 days were consecutive. If the first morning catheterized volume was recorded on 1 single day of the weekend e-diary, the average morning catheterized is the first morning catheterized that day. If no first morning catheterized

Change at Week 2
GroupValue95% CI
Children (3 to < 12 Years)7.98± 101.36
Adolescents (12 to < 18 Years)39.52± 80.24
Change at Week 4
GroupValue95% CI
Children (3 to < 12 Years)19.81± 89.04
Adolescents (12 to < 18 Years)75.25± 105.72
Change at Week 8
GroupValue95% CI
Children (3 to < 12 Years)34.01± 89.53
Adolescents (12 to < 18 Years)44.43± 89.01
Change at Week 12
GroupValue95% CI
Children (3 to < 12 Years)8.68± 80.16
Adolescents (12 to < 18 Years)38.23± 66.80
Change at Week 24
GroupValue95% CI
Children (3 to < 12 Years)40.76± 116.41
Adolescents (12 to < 18 Years)86.66± 96.55
Change at Week 36
GroupValue95% CI
Children (3 to < 12 Years)31.08± 145.63
Adolescents (12 to < 18 Years)68.47± 122.43
Change at Week 52
GroupValue95% CI
Children (3 to < 12 Years)31.83± 94.25
Adolescents (12 to < 18 Years)38.14± 108.06

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first dose of study drug administration up to end-of-treatment (EoT) (up to week 52).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Children (3 to < 12 Years)
Serious: 9/55 (16%)
Deaths: 0/55
Adolescents (12 to < 18 Years)
Serious: 5/31 (16%)
Deaths: 0/31

Serious adverse events (18 terms)

ReactionSystemChildren (3 to < 12 Years)Adolescents (12 to < 18 Ye…
Device malfunctionGeneral disorders
TalipesCongenital, familial and genetic disorders
ColitisGastrointestinal disorders
PyrexiaGeneral disorders
AppendicitisInfections and infestations
BronchitisInfections and infestations
Escherichia urinary tract infectionInfections and infestations
Pneumonia bacterialInfections and infestations
Pyelonephritis acuteInfections and infestations
Viral infectionInfections and infestations
Shunt malfunctionInjury, poisoning and procedural complications
Benign neoplasm of skinNeoplasms benign, malignant and unspecified (incl cysts and polyps)
ConvulsionNervous system disorders
HydrocephalusNervous system disorders
Urethral perforationRenal and urinary disorders
EpididymitisReproductive system and breast disorders
Rash generalisedSkin and subcutaneous tissue disorders
Talipes correctionSurgical and medical procedures
Other adverse events (8 terms — click to expand)

ReactionSystemChildren (3 to < 12 Years)Adolescents (12 to < 18 Ye…
Escherichia urinary tract infectionInfections and infestations
Respiratory tract infection viralInfections and infestations
Urinary tract infectionInfections and infestations
Urinary tract infection bacterialInfections and infestations
ConstipationGastrointestinal disorders
NasopharyngitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
PyrexiaGeneral disorders

Most-reported serious reactions: Device malfunction, Talipes, Colitis, Pyrexia, Appendicitis, Bronchitis, Escherichia urinary tract infection, Pneumonia bacterial.

Data from ClinicalTrials.gov NCT02751931 adverse events section.

Sponsor's own description

The objective of the study was to evaluate the efficacy, safety, tolerability and pharmacokinetics of mirabegron after multiple-dose administration in the pediatric population.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

  1. Efficacy and safety of mirabegron in children and adolescents with neurogenic detrusor overactivity: An open-label, phase 3, dose-titration study.
    Baka-Ostrowska M, Bolong DT, Persu C, Tøndel C, et al · · 2021 · cited 12× · PMID 34058027 · DOI 10.1002/nau.24657

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Other trials of Mirabegron

Trials testing the same drug.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02751931.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing