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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT02751931
Additional trial details provided through ANZCTR are available at the end of this record.
Registration number
NCT02751931
Ethics application status
Date submitted
22/04/2016
Date registered
26/04/2016
Date last updated
20/10/2022
Titles & IDs
Public title
Open-label Phase 3 Study With Mirabegron in Children From 3 to Less Than 18 Years of Age With Neurogenic Detrusor Overactivity
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Scientific title
An Open-label, Baseline-controlled, Multicenter, Phase 3 Dose-titration Study Followed by a Fixed-dose Observation Period to Evaluate Efficacy, Safety and Pharmacokinetics of Mirabegron in Children and Adolescents From 3 to Less Than 18 Years of Age With Neurogenic Detrusor Overactivity (NDO) on Clean Intermittent Catheterization (CIC)
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Secondary ID [1]
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2015-002876-25
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Secondary ID [2]
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178-CL-206A
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Universal Trial Number (UTN)
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Trial acronym
Crocodile
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Neurogenic Detrusor Overactivity
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Condition category
Condition code
Renal and Urogenital
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Other renal and urogenital disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Mirabegron
Experimental: Children (3 to < 12 Years) - Participants aged 3 to < 12 years received initial dose of 25 milligram (mg) of mirabegron orally once daily based on weight (pediatric equivalent dose of 25 mg (milligram) [PED25]) on day 1. At weeks 2, 4 or 8, participant's were up-titrated to the pediatric equivalent dose of 50 mg in adults [PED50], orally once daily based on the given dose titration criteria. Following week 24, participants stayed on their individual dose level until week 52 end-of-study (EOS) or end-of-treatment (EOT).
Experimental: Adolescents (12 to < 18 Years) - Participants aged 12 to < 18 years received initial dose of 25 mg of mirabegron orally once daily based on weight [PED25] on day 1. At weeks 2, 4 or 8, participant's were up-titrated to the pediatric equivalent dose of 50 mg in adults [PED50] orally once daily based on the given dose titration criteria. Following week 24, participants stayed on their individual dose level until week 52 EOS or EOT.
Treatment: Drugs: Mirabegron
Participants received initial dose of 25 mg of mirabegron PED25 orally once daily. At weeks 2, 4 or 8, participants were up-titrated to PED50 based on the given dose titration criteria. Following week 24, participants stayed on their individual dose level until week 52 EOS or EOT. Participants with a body weight >=35 kg received mirabegron tablets or body weight <35 kg received mirabegron oral suspension. At week 24, participants on mirabegron oral suspension could switch to tablets if the body weight became >=35 kg or participants on mirabegron tablets could switch to oral suspension if the body weight became <35 Kg or participants could switch to either of the dosage form for acceptability reasons after sponsor's prior approval and on a case-by-case basis. Mirabegron extended-release granules were reconstituted with water to prepare a mirabegron oral suspension of 8 mg/mL. Administration was via an oral syringe with a sip of water afterwards.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Change From Baseline in Maximum Cystometric Capacity (MCC) at Week 24
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Assessment method [1]
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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).
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Timepoint [1]
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Baseline and week 24
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Secondary outcome [1]
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Change From Baseline in Bladder Compliance (?V/?P)
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Assessment method [1]
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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% of maximum catheterized volume for age had been reached. A valid urodynamic assessment was confirmed valid by the central reviewers.
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Timepoint [1]
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Baseline and weeks 4 and 24
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Secondary outcome [2]
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Change From Baseline in Maximum Cystometric Capacity at Week 4
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Assessment method [2]
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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.
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Timepoint [2]
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Baseline and week 4
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Secondary outcome [3]
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Change From Baseline in Number of Overactive Detrusor Contractions (> 15 cm H20) Until End of Filling
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Assessment method [3]
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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.
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Timepoint [3]
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Baseline and weeks 4 and 24
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Secondary outcome [4]
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Change From Baseline in Detrusor Pressure at End of Filling
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Assessment method [4]
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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 urodynamic assessment was confirmed valid by the central reviewers.
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Timepoint [4]
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Baseline and weeks 4 and 24
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Secondary outcome [5]
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Change From Baseline in Filling Bladder Volume Until First Overactive Detrusor Contraction (> 15 cm H20)
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Assessment method [5]
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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.
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Timepoint [5]
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Baseline and weeks 4 and 24
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Secondary outcome [6]
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Change From Baseline in Filling Bladder Volume Until First Overactive Detrusor Contraction (> 15 cm H20): Wilcoxon Signed-rank Test Updated Analysis
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Assessment method [6]
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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 analysis of bladder volume until first detrusor contraction (> 15 cm H2O) did not impute missing bladder volume data with the maximum cystometric capacity (MCC) value at that visit according to the statistical analysis plan (SAP). This analysis was updated to impute missing values for volume at first contraction with respective MCC values.
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Timepoint [6]
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Baseline and weeks 4 and 24
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Secondary outcome [7]
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Change From Baseline in Filling Bladder Volume Until First Overactive Detrusor Contraction (> 15 cm H20): Paired T-test
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Assessment method [7]
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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.
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Timepoint [7]
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Baseline and weeks 4 and 24
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Secondary outcome [8]
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Change From Baseline in Average Catheterized Volume Per Catheterization
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Assessment method [8]
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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 catheterized volume per catheterization was missing. A valid bladder diary day in the weekend diary was any e-diary day for which =1 catheterized volume >0 mL was recorded with complete date and time.
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Timepoint [8]
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Baseline and weeks 2, 4, 8, 12, 24, 36 and 52
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Secondary outcome [9]
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Change From Baseline in Maximum Catheterized Volume
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Assessment method [9]
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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 catheterized volume per day was missing. A valid bladder diary day in the weekend diary was any e-diary day for which >=1 catheterized volume >0 mL was recorded with complete date and time.
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Timepoint [9]
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Baseline and weeks 2, 4, 8, 12, 24, 36 and 52
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Secondary outcome [10]
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Change From Baseline in Maximum Catheterized Daytime Volume (MCDV)
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Assessment method [10]
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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 time (minus 30 min) & time to sleep (plus 29 min) recorded in the e-diary. A valid bladder diary day in the weekend diary was any e-diary day for which >=1 catheterized volume >0 mL was recorded with complete date and time.
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Timepoint [10]
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Baseline and weeks 2, 4, 8, 12, 24, 36 and 52
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Secondary outcome [11]
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Change From Baseline in Average Morning Catheterized Volume
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Assessment method [11]
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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 volumes are recorded on any day of the weekend e-diary, the average first morning catheterized volume was missing. A valid bladder diary day in the weekend diary was any e-diary day for which >=1 catheterized volume >0 mL was recorded with complete date and time.
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Timepoint [11]
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Baseline and weeks 2, 4, 8, 12, 24, 36 and 52
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Secondary outcome [12]
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Change From Baseline in Mean Number of Leakage Episodes Per Day
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Assessment method [12]
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For each participant, the mean number of leakage episodes per day (during day & night time) was calculated using all available/non-missing number of leakage episodes for the 2 measuring days in the weekend diary during day & night time. If the number of leakage episodes was recorded on 1 single day in the 7-day diary during day & night time, the mean number of leakage episodes per day during day & night time is equal to the total number of leakage episodes recorded that day during day & night time. If no leakage episodes were recorded on any day of the weekend diary during day & night time, the mean number of leakage episodes per day was zero. Participants who did not report any leakage episode during the visit were imputed with a '0' for that visit. A valid bladder diary day in the weekend diary was any e-diary day for which =1 catheterized volume >0 mL was recorded with complete date and time.
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Timepoint [12]
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Baseline and weeks 2, 4, 8, 12, 24, 36 and 52
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Secondary outcome [13]
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Change From Baseline in Mean Number of Leakage Episodes Per Day: Updated Analysis
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Assessment method [13]
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For each participant, the mean number(no.) of leakage episodes per day (during day & night time) was calculated using all available/non-missing no. of leakage episodes for the 2 measuring days in the weekend diary during day & night time. If the no. of leakage episodes was recorded on 1 single day in the 7-day diary during day & night time, the mean no. of leakage episodes per day during day & night time is equal to the total no. of leakage episodes recorded that day during day & night time. If no leakage episodes were recorded on any day of the weekend diary during day & night time, the mean no. of leakage episodes per day was zero. Participants who did not report leakage episode during the visit were imputed with a '0' for that visit. A valid bladder diary day in weekend diary was any e-diary day for which =1 catheterized volume >0 mL was recorded with complete date and time. Updated analysis is presented because one participant entered weight of leakage instead of no. of leakages.
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Timepoint [13]
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Baseline and weeks 2, 4, 8, 12, 24, 36 and 52
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Secondary outcome [14]
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Change From Baseline in Number of Dry Days Per 7 Days (Day and Night Time)
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Assessment method [14]
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Dry days were defined as leakage-free days, this included day and night time. Participants recorded dry days in the 7-day diary. Dry days were calculated as follows: Ddry was the number of valid diary days where the response to the question 'Did you leak between this catheterization and the last one' was 'No' each time a new catheterization was entered in the e-diary during the day & night time period. Dwet was the number of valid diary days where the response to the question 'Did you leak between this catheterization and the last one' was 'Yes' for at least one catheterization entered during the day and night time period. If (Ddry + Dwet) > 3, the number of dry days per 7 days was calculated as Ddry/(Ddry + Dwet) x 7, otherwise the value was missing.
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Timepoint [14]
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Baseline and weeks 2, 4, 8, 12, 24, 36 and 52
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Secondary outcome [15]
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Change From Baseline in Pediatric Incontinence Questionnaire (PIN-Q) Score
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Assessment method [15]
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PIN-Q measured quality of life via an e-diary. Total score ranged from 0 (no effect) to 80 (worst effect); decrease in score indicated improvement. Total score was 20x average of individual PinQ items, the 20 Likert scales were converted to a score: Items 6 & 17; 0: "No" to 4: "Definitely" was used; & For the other 18 items; 0: "No" to 4: "All the time" was used. Expectation that questionnaires had limited missing values; if answers >2 questions were missing, total score was not calculated & was missing. Individual item scores were directly imputed. Change from baseline to each post-baseline visit in the total score was post-baseline visit value minus baseline value. If either baseline or post-baseline visit value was missing, change from baseline was missing. If change was: <0, improvement between 2 time-points; =0, no change between 2 time points; >0, worsening between 2 time points.
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Timepoint [15]
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Baseline and weeks 24 and 52
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Secondary outcome [16]
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Change From Baseline in Patient Global Impression of Severity Scale (PGI-S)
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Assessment method [16]
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The PGI-S was an answer to the question: "How did you feel about your bladder condition during the past 3 days?" Participants evaluated their recent condition as "Really Bad"(0), "Bad" (1), "Not Bad, Not Good" (2), "Good" (3) &"Really Good" (4). An increase indicated improvement. The total score ranged from 0 to 4, where higher scores indicated improvement.The change from baseline to each postbaseline visit in the PGI-S score is the value at the post-baseline visit minus the value at the baseline visit. If either the baseline or the post-baseline visit value is missing, the change from baseline was missing. A positive change indicated an improvement while a negative change indicated a worsening.
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Timepoint [16]
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Baseline and weeks 24 and 52
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Secondary outcome [17]
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Number of Participants With Clinician Global Impression of Change (CGI-C)
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Assessment method [17]
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The Clinician Global Impression of Change (CGI-C) is a 7 point scale that required the clinician to assess how much the participant's overall bladder symptoms since the start of the study on day 1 has improved or worsened and rated as: very much improved (1); much improved (2); minimally improved (3); no change (4); minimally worse (5); much worse (6); or very much worse (7). The total score range from 1-7, where lower scores indicated improvement.
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Timepoint [17]
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Weeks 24 and 52
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Secondary outcome [18]
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Number of Participants With Study Drug Acceptability for Tablets at Week 4
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Assessment method [18]
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Participants evaluated the taste of the study medication/tablets by ticking 1 of the following categories: "Really Bad" (0), "Bad" (1), "Not Bad, Not Good" (2), "Good" (3) & "Really Good" (4). Participants evaluated the swallow of the study medication/tablets by ticking one of the following categories: "Really Difficult" (0), "Difficult" (1), "Not Difficult, Not Easy" (2), "Easy" (3) and "Really Easy" (4).
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Timepoint [18]
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Week 4
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Secondary outcome [19]
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Number of Participants With Study Drug Acceptability for Tablets at Week 24
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Assessment method [19]
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Participants evaluated the taste of the study medication/tablets by ticking 1 of the following categories: "Really Bad" (0), "Bad" (1), "Not Bad, Not Good" (2), "Good" (3) & "Really Good" (4). Participants evaluated the swallow of the study medication/tablets by ticking one of the following categories: "Really Difficult" (0), "Difficult" (1), "Not Difficult, Not Easy" (2), "Easy" (3) and "Really Easy" (4).
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Timepoint [19]
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Week 24
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Secondary outcome [20]
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Number of Participants With Study Drug Acceptability for Tablets at Week 52
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Assessment method [20]
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Participants evaluated the taste of the study medication/tablets by ticking 1 of the following categories: "Really Bad" (0), "Bad" (1), "Not Bad, Not Good" (2), "Good" (3) & "Really Good" (4). Participants evaluated the swallow of the study medication/tablets by ticking one of the following categories: "Really Difficult" (0), "Difficult" (1), "Not Difficult, Not Easy" (2), "Easy" (3) and "Really Easy" (4).
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Timepoint [20]
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Week 52
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Secondary outcome [21]
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Number of Participants With Study Drug Acceptability for Oral Suspension at Week 4
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Assessment method [21]
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Participants evaluated the taste of the study medication/oral suspension by ticking 1 of the following categories:"Really Bad" (0), "Bad" (1), "Not Bad, Not Good" (2), "Good" (3) & "Really Good" (4). Participants evaluated the smell of the study medication/oral suspension by ticking 1 of the following categories: "Really Bad" (0), "Bad" (1),"Not Bad, Not Good" (2), "Good" (3) & "Really Good" (4). Participants evaluated the consumption and the preparation of the study medication/oral suspension by ticking 1 of the following categories: "Really Difficult" (0),"Difficult" (1), "Not Difficult, Not Easy" (2), "Easy" (3) & "Really Easy" (4).
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Timepoint [21]
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Week 4
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Secondary outcome [22]
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Number of Participants With Study Drug Acceptability for Oral Suspension at Week 24
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Assessment method [22]
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Participants evaluated the taste of the study medication/oral suspension by ticking 1 of the following categories:"Really Bad" (0), "Bad" (1), "Not Bad, Not Good" (2), "Good" (3) & "Really Good" (4). Participants evaluated the smell of the study medication/oral suspension by ticking 1 of the following categories: "Really Bad" (0), "Bad" (1),"Not Bad, Not Good" (2), "Good" (3) & "Really Good" (4). Participants evaluated the consumption and the preparation of the study medication/oral suspension by ticking 1 of the following categories: "Really Difficult" (0),"Difficult" (1), "Not Difficult, Not Easy" (2), "Easy" (3) & "Really Easy" (4).
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Timepoint [22]
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Week 24
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Secondary outcome [23]
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Number of Participants With Study Drug Acceptability for Oral Suspension at Week 52
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Assessment method [23]
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Participants evaluated the taste of the study medication/oral suspension by ticking 1 of the following categories:"Really Bad" (0), "Bad" (1), "Not Bad, Not Good" (2), "Good" (3) & "Really Good" (4). Participants evaluated the smell of the study medication/oral suspension by ticking 1 of the following categories: "Really Bad" (0), "Bad" (1),"Not Bad, Not Good" (2), "Good" (3) & "Really Good" (4). Participants evaluated the consumption and the preparation of the study medication/oral suspension by ticking 1 of the following categories: "Really Difficult" (0),"Difficult" (1), "Not Difficult, Not Easy" (2), "Easy" (3) & "Really Easy" (4).
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Timepoint [23]
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Week 52
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Secondary outcome [24]
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Number of Participants With Adverse Events (AEs)
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Assessment method [24]
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An AE was defined as any untoward medical occurrence in a participant who was given the study drug or who had undergone study procedures and did not necessarily have a causal relationship with this treatment. An AE could therefore be any unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A treatment-emergent adverse event (TEAE) was defined as any AE with date of onset occurring on or after the first dose of study medication and up to the end of study.
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Timepoint [24]
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From the first dose of study drug administration up to end-of-treatment (EoT) (up to week 52)
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Secondary outcome [25]
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Maximum Plasma Concentration (Cmax) of Mirabegron
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Assessment method [25]
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Cmax was defined as the maximum plasma concentration of mirabegron.
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Timepoint [25]
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A total of 4 samples were collected over 2 sampling days at 2 separate visits at any of week 4, 8, 12, 24, 36, or 52, at the following time points: Sampling day 1- Predose; Sampling day 2- Predose and 2 samples 2-5 hours postdose more than 1 hour apart.
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Secondary outcome [26]
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Time to Reach Maximum Plasma Concentration of Mirabegron Following Drug Administration (Tmax)
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Assessment method [26]
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Tmax was defined as the time to reach maximum plasma concentration following drug administration.
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Timepoint [26]
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A total of 4 samples were collected over 2 sampling days at 2 separate visits at any of week 4, 8, 12, 24, 36, or 52, at the following time points: Sampling day 1- Predose; Sampling day 2- Predose and 2 samples 2-5 hours postdose more than 1 hour apart.
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Secondary outcome [27]
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Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC24) for Mirabegron
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Assessment method [27]
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AUC (0-24) is the area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours post-dose.
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Timepoint [27]
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A total of 4 samples were collected over 2 sampling days at 2 separate visits at any of week 4, 8, 12, 24, 36, or 52, at the following time points: Sampling day 1- Predose; Sampling day 2- Predose and 2 samples 2-5 hours postdose more than 1 hour apart.
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Secondary outcome [28]
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Plasma Concentration of Mirabegron at the End of a Dosing Interval at Steady State (Ctrough)
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Assessment method [28]
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Ctrough was defined as the measured plasma concentration of mirabegron at the end of a dosing interval at steady state.
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Timepoint [28]
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0
A total of 4 samples were collected over 2 sampling days at 2 separate visits at any of week 4, 8, 12, 24, 36, or 52, at the following time points: Sampling day 1- Predose; Sampling day 2- Predose and 2 samples 2-5 hours postdose more than 1 hour apart.
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Secondary outcome [29]
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Apparent Total Clearance of Mirabegron From Plasma After Oral Administration (CL/F)
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Assessment method [29]
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Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
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Timepoint [29]
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A total of 4 samples were collected over 2 sampling days at 2 separate visits at any of week 4, 8, 12, 24, 36, or 52, at the following time points: Sampling day 1- Predose; Sampling day 2- Predose and 2 samples 2-5 hours postdose more than 1 hour apart.
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Secondary outcome [30]
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Apparent Volume of Distribution After Non-intravenous Administration (Vz/F) of Mirabegron
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Assessment method [30]
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Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
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Timepoint [30]
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0
A total of 4 samples were collected over 2 sampling days at 2 separate visits at any of week 4, 8, 12, 24, 36, or 52, at the following time points: Sampling day 1- Predose; Sampling day 2- Predose and 2 samples 2-5 hours postdose more than 1 hour apart.
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Eligibility
Key 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
Query!
Minimum age
3
Years
Query!
Query!
Maximum age
17
Years
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key 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 < 30 mL/min).
- Subject's aspartate aminotransferase (AST) or alanine aminotransferase (ALT) is
greater than or equal to 2 times the upper limit of normal (ULN) or total bilirubin
(TBL) greater than or equal to 1.5 times the ULN according to age and sex.
- Subject has a history or presence of any malignancy prior to visit 1/screening.
- Subject has known or suspected hypersensitivity to mirabegron, any of the excipients
used in the current formulations or previous severe hypersensitivity to any drug.
- Subject has participated in another clinical trial (and/or has taken an
investigational drug within 30 days (or 5 half-lives of the drug, or the limit set by
national law, whichever is longer) prior to visit 1/screening.
- Subject uses any of the following prohibited medications (after start of washout):
- Any medication, other than the study drug used, for the management of NDO;
- Any drugs that are sensitive CYP2D6 substrates with a narrow therapeutic index or
sensitive P-glycoprotein (P-gp) substrates
- Any strong CYP3A4 inhibitors if the subject has a mild to moderate renal
impairment (eGFR 30 - 89 mL/min).
- Subject has been administered intravesical botulinum toxin; except if given > 4 months
prior to visit 1/screening and the subject experiences symptoms comparable to those
existing prior to the botulinum toxin injections.
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Non-randomised trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Single group
Query!
Other design features
Query!
Phase
Phase 3
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
17/06/2016
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
6/05/2019
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
91
Query!
Recruitment in Australia
Recruitment state(s)
NSW
Query!
Recruitment hospital [1]
0
0
Site AU61002 - Randwick
Query!
Recruitment postcode(s) [1]
0
0
2031 - Randwick
Query!
Recruitment outside Australia
Country [1]
0
0
Belgium
Query!
State/province [1]
0
0
Edegem
Query!
Country [2]
0
0
Belgium
Query!
State/province [2]
0
0
Gent
Query!
Country [3]
0
0
Croatia
Query!
State/province [3]
0
0
Zagreb
Query!
Country [4]
0
0
Denmark
Query!
State/province [4]
0
0
Aarhus N
Query!
Country [5]
0
0
Denmark
Query!
State/province [5]
0
0
Copenhagen
Query!
Country [6]
0
0
Israel
Query!
State/province [6]
0
0
Jerusalem
Query!
Country [7]
0
0
Jordan
Query!
State/province [7]
0
0
Amman
Query!
Country [8]
0
0
Jordan
Query!
State/province [8]
0
0
Irbid
Query!
Country [9]
0
0
Korea, Republic of
Query!
State/province [9]
0
0
Seoul
Query!
Country [10]
0
0
Latvia
Query!
State/province [10]
0
0
Riga
Query!
Country [11]
0
0
Lithuania
Query!
State/province [11]
0
0
Kaunas
Query!
Country [12]
0
0
Lithuania
Query!
State/province [12]
0
0
Vilnius
Query!
Country [13]
0
0
Malaysia
Query!
State/province [13]
0
0
Georgetown
Query!
Country [14]
0
0
Malaysia
Query!
State/province [14]
0
0
Kuala Lumpur
Query!
Country [15]
0
0
Mexico
Query!
State/province [15]
0
0
Mexico City
Query!
Country [16]
0
0
Norway
Query!
State/province [16]
0
0
Bergen
Query!
Country [17]
0
0
Philippines
Query!
State/province [17]
0
0
Quezon City
Query!
Country [18]
0
0
Poland
Query!
State/province [18]
0
0
Gdansk
Query!
Country [19]
0
0
Poland
Query!
State/province [19]
0
0
Warszawa
Query!
Country [20]
0
0
Romania
Query!
State/province [20]
0
0
Bucuresti
Query!
Country [21]
0
0
Serbia
Query!
State/province [21]
0
0
Nis
Query!
Country [22]
0
0
Serbia
Query!
State/province [22]
0
0
Novi Sad
Query!
Country [23]
0
0
Slovakia
Query!
State/province [23]
0
0
Bratislava
Query!
Country [24]
0
0
Taiwan
Query!
State/province [24]
0
0
New Taipei City
Query!
Country [25]
0
0
Turkey
Query!
State/province [25]
0
0
Ankara
Query!
Country [26]
0
0
Turkey
Query!
State/province [26]
0
0
Bursa
Query!
Country [27]
0
0
Turkey
Query!
State/province [27]
0
0
Mersin
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
Astellas Pharma Europe B.V.
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief 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.
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT02751931
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Medical Monitor
Query!
Address
0
0
Astellas Pharma Europe B.V.
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02751931
Additional trial details provided through ANZCTR
Accrual to date
Recruitment state(s)
Funding & Sponsors
Primary sponsor
Primary sponsor name
Primary sponsor address
Primary sponsor country
Ethics approval
Ethics application status
Public notes
Please refer to ClinicalTrials.gov website link (https://clinicaltrials.gov/ct2/show/results/NCT02751931?term=178-cl-206a&draw=2&rank=1) and EU CTR website link (https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-002876-25/results) or the Astellas Website (www.astellasclinicalstudyresults.com) for results.
Contacts
Principal investigator
Title
361
0
Query!
Name
361
0
Query!
Address
361
0
Query!
Country
361
0
Query!
Phone
361
0
Query!
Fax
361
0
Query!
Email
361
0
Query!
Contact person for public queries
Title
362
0
Query!
Name
362
0
Query!
Address
362
0
Query!
Country
362
0
Query!
Phone
362
0
Query!
Fax
362
0
Query!
Email
362
0
Query!
Contact person for scientific queries
Title
363
0
Query!
Name
363
0
Query!
Address
363
0
Query!
Country
363
0
Query!
Phone
363
0
Query!
Fax
363
0
Query!
Email
363
0
Query!
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