Clinical Trial Results:
A Randomized, Active-controlled, Open-label, Flexible-dose Study to Assess the Safety and Tolerability of Topiramate as Monotherapy Compared With Levetiracetam as Monotherapy in Pediatric Subjects With New or Recent-onset Epilepsy
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Summary
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EudraCT number |
2012-001552-19 |
Trial protocol |
AT IT HU BE DE GB FR PL |
Global end of trial date |
30 Apr 2020
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Results information
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Results version number |
v1 |
This version publication date |
14 Nov 2020
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First version publication date |
14 Nov 2020
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Other versions |
v2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
TOPMATEPY4067
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02201251 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Janssen Research & Development, LLC
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Sponsor organisation address |
920 Route 202 NJ, Raritan, United States,
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Public contact |
Clinical Registry Group, Janssen Research & Development, LLC, ClinicalTrialsEU@its.jnj.com
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Scientific contact |
Clinical Registry Group, Janssen Research & Development, LLC, ClinicalTrialsEU@its.jnj.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
10 Jun 2020
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Apr 2020
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The main objective of this study was to evaluate the effects of topiramate monotherapy compared with levetiracetam another standard antiepileptic drug (AED), as monotherapy for new-onset or recent-onset epilepsy (seizure disorder) on pediatric growth and maturation, bone mineralization, and kidney stone formation in children aged 2 to 15 years.
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Protection of trial subjects |
This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements. Safety evaluations included monitoring of adverse events (AEs), vital sign measurements, electrocardiogram (ECG), clinical laboratory parameters, dual-energy X-ray absorptiometry (DEXA) scan, renal ultrasound, biochemical bone markers, hand/wrist x-ray, Tanner staging, cognitive, developmental, and behavioral assessments, and physical examinations.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
30 Apr 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Austria: 2
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Country: Number of subjects enrolled |
Canada: 1
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Country: Number of subjects enrolled |
Hungary: 9
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Country: Number of subjects enrolled |
Italy: 7
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Country: Number of subjects enrolled |
Philippines: 3
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Country: Number of subjects enrolled |
Poland: 16
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Country: Number of subjects enrolled |
Russian Federation: 6
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Country: Number of subjects enrolled |
Taiwan: 17
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Country: Number of subjects enrolled |
United States: 2
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Worldwide total number of subjects |
63
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EEA total number of subjects |
34
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
47
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Adolescents (12-17 years) |
16
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 114 subjects were screened. Out of 114 screened subjects, 63 subjects (topiramate group: 28 subjects, levetiracetam group: 35 subjects) were randomized in the study and received at least 1 dose of study drug. | ||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Topiramate | ||||||||||||||||||||||||
Arm description |
Subjects received topiramate weight-based sprinkle capsule and tablet, as tolerated (not to exceed 350 milligrams per day [mg/day] for subjects 2 to less than [<] 10 years of age, and not to exceed 400 mg/day for subjects 10 to 15 years of age), twice daily (BID) for up to 1 year during open-label treatment phase. Subjects were to either continue on commercially available topiramate or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Topiramate
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Topiramate BID for up to 1 year during open-label treatment phase was administered.
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Arm title
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Levetiracetam | ||||||||||||||||||||||||
Arm description |
Subjects received levetiracetam weight-based tablet or oral solution, as tolerated (not to exceed 60 milligrams per kilogram per day [mg/kg/day] for subjects 2 to 15 years of age). The daily dosage was increased every 2 weeks by increments of 20 mg/kg/day to the recommended daily dosage of 60 mg/kg/day. The maximum recommended daily dosage was 3000 mg (1500 mg BID) for up to 1 year during open-label treatment phase. Subjects were to either continue on commercially available levetiracetam or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days. | ||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||
Investigational medicinal product name |
Levetiracetam
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral solution, Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Levetiracetam every 2 weeks by increments of 20 mg/kg/day to the recommended daily dosage for up to 1 year during open-label treatment phase was administered.
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Baseline characteristics reporting groups
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Reporting group title |
Topiramate
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Reporting group description |
Subjects received topiramate weight-based sprinkle capsule and tablet, as tolerated (not to exceed 350 milligrams per day [mg/day] for subjects 2 to less than [<] 10 years of age, and not to exceed 400 mg/day for subjects 10 to 15 years of age), twice daily (BID) for up to 1 year during open-label treatment phase. Subjects were to either continue on commercially available topiramate or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Levetiracetam
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Reporting group description |
Subjects received levetiracetam weight-based tablet or oral solution, as tolerated (not to exceed 60 milligrams per kilogram per day [mg/kg/day] for subjects 2 to 15 years of age). The daily dosage was increased every 2 weeks by increments of 20 mg/kg/day to the recommended daily dosage of 60 mg/kg/day. The maximum recommended daily dosage was 3000 mg (1500 mg BID) for up to 1 year during open-label treatment phase. Subjects were to either continue on commercially available levetiracetam or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Topiramate
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Reporting group description |
Subjects received topiramate weight-based sprinkle capsule and tablet, as tolerated (not to exceed 350 milligrams per day [mg/day] for subjects 2 to less than [<] 10 years of age, and not to exceed 400 mg/day for subjects 10 to 15 years of age), twice daily (BID) for up to 1 year during open-label treatment phase. Subjects were to either continue on commercially available topiramate or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days. | ||
Reporting group title |
Levetiracetam
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Reporting group description |
Subjects received levetiracetam weight-based tablet or oral solution, as tolerated (not to exceed 60 milligrams per kilogram per day [mg/kg/day] for subjects 2 to 15 years of age). The daily dosage was increased every 2 weeks by increments of 20 mg/kg/day to the recommended daily dosage of 60 mg/kg/day. The maximum recommended daily dosage was 3000 mg (1500 mg BID) for up to 1 year during open-label treatment phase. Subjects were to either continue on commercially available levetiracetam or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days. | ||
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End point title |
Change From Baseline in Weight Z-score at Month 1 [1] | ||||||||||||
End point description |
The Z-Score indicates how many standard deviations (SD) a subject was from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the Statistical Analysis System (SAS) programs provided by the Centers for Disease Control (CDC) for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline by visit for the total safety population for all age cohorts combined were presented. The safety analysis set included all randomized subjects who received at least 1 dose of study drug. Here, N (Number of Subjects Analyzed) signifies number of subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline, Month 1
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistical analyses was planned to report for the primary end point. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Weight Z-score at Month 3 [2] | ||||||||||||
End point description |
The Z-Score indicates how many SD a subject was from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline by visit for the total safety population for all age cohorts combined were presented. The safety analysis set included all randomized subjects who received at least 1 dose of study drug. Here, N (Number of Subjects Analyzed) signifies number of subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline, Month 3
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistical analyses was planned to report for the primary end point. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Weight Z-score at Month 6 [3] | ||||||||||||
End point description |
The Z-Score indicates how many SD a subject was from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline by visit for the total safety population for all age cohorts combined were presented. The safety analysis set included all randomized subjects who received at least 1 dose of study drug. Here, N (Number of Subjects Analyzed) signifies number of subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline, Month 6
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistical analyses was planned to report for the primary end point. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Weight Z-score at Month 9 [4] | ||||||||||||
End point description |
The Z-Score indicates how many SD a subject was from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline by visit for the total safety population for all age cohorts combined were presented. The safety analysis set included all randomized subjects who received at least 1 dose of study drug. Here, N (Number of Subjects Analyzed) signifies number of subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline, Month 9
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistical analyses was planned to report for the primary end point. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Weight Z-score at Month 12 [5] | ||||||||||||
End point description |
The Z-Score indicates how many SD a subject was from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline by visit for the total safety population for all age cohorts combined were presented. The safety analysis set included all randomized subjects who received at least 1 dose of study drug. Here, N (Number of Subjects Analyzed) signifies number of subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline, Month 12
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistical analyses was planned to report for the primary end point. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Height Z-score at Month 1 [6] | ||||||||||||
End point description |
Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from minus (-) 3 to plus (+) 3; 0 equal to (=) same mean, greater than (>) 0 a greater mean, and less than (<) 0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline by visit for the total safety population for all age cohorts combined were presented. The safety analysis set included all randomized subjects who received at least 1 dose of study drug. Here, N (Number of Subjects Analyzed) signifies number of subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline, Month 1
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| Notes [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistical analyses was planned to report for the primary end point. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Height Z-score at Month 3 [7] | ||||||||||||
End point description |
Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, >0 a greater mean, and <0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline by visit for the total safety population for all age cohorts combined were presented. The safety analysis set included all randomized subjects who received at least 1 dose of study drug. Here, N (Number of Subjects Analyzed) signifies number of subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline, Month 3
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| Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistical analyses was planned to report for the primary end point. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Height Z-score at Month 6 [8] | ||||||||||||
End point description |
Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, >0 a greater mean, and <0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline by visit for the total safety population for all age cohorts combined were presented. The safety analysis set included all randomized subjects who received at least 1 dose of study drug. Here, N (Number of Subjects Analyzed) signifies number of subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline, Month 6
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| Notes [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistical analyses was planned to report for the primary end point. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Height Z-score at Month 9 [9] | ||||||||||||
End point description |
Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, >0 a greater mean, and <0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline by visit for the total safety population for all age cohorts combined were presented. The safety analysis set included all randomized subjects who received at least 1 dose of study drug. Here, N (Number of Subjects Analyzed) signifies number of subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline, Month 9
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| Notes [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistical analyses was planned to report for the primary end point. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Height Z-score at Month 12 [10] | ||||||||||||
End point description |
Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, >0 a greater mean, and <0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline by visit for the total safety population for all age cohorts combined were presented. The safety analysis set included all randomized subjects who received at least 1 dose of study drug. Here, N (Number of Subjects Analyzed) signifies number of subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline, Month 12
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| Notes [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistical analyses was planned to report for the primary end point. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from Baseline in Bone Mineral Density (BMD) Z-score at Month 6 [11] | ||||||||||||||||||
End point description |
The BMD was measured by dual energy X-ray absorptiometry (DEXA) for the posterior-anterior lumbar spine (L1_L4) and total body less head area. The Z-Score is the number of standard deviations a subject's BMD differs from the average BMD of their age, sex and ethnicity. Positive scores indicate BMD above the mean; positive values are "best values" and negative values are "worst values". Positive changes from baseline indicated an improvement in condition. The safety analysis set included all randomized subjects who received at least 1 dose of study drug. Here, n (number analyzed) signifies number of subjects evaluable for this endpoint for specified category.
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End point type |
Primary
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End point timeframe |
Baseline, Month 6
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| Notes [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistical analyses was planned to report for the primary end point. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change from Baseline in BMD Z-score at Month 12 [12] | ||||||||||||||||||
End point description |
The BMD was measured by DEXA for the posterior-anterior lumbar spine (L1_L4) and total body less head area. The Z-Score is the number of standard deviations a subject's BMD differs from the average BMD of their age, sex and ethnicity. Positive scores indicate BMD above the mean; positive values are "best values" and negative values are "worst values". Positive changes from baseline indicated an improvement in condition. The safety analysis set included all randomized subjects who received at least 1 dose of study drug. Here, n (number analyzed) signifies number of subjects evaluable for this endpoint for specified category.
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End point type |
Primary
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End point timeframe |
Baseline, Month 12
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| Notes [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistical analyses was planned to report for the primary end point. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change From Baseline in Bone Mineral Content (BMC)-Z Score at Month 6 [13] | ||||||||||||||||||
End point description |
The BMC is an estimate of the amount of mineral (such as calcium) in the bone, which was assessed by DEXA scan for the posterior-anterior lumbar spine (L1_L4) and total body less head area. Positive changes from baseline indicated an improvement in condition. The safety analysis set included all randomized subjects who received at least 1 dose of study drug. Here, n (number analyzed) signifies number of subjects evaluable for this endpoint for specified category.
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End point type |
Primary
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End point timeframe |
Baseline, Month 6
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| Notes [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistical analyses was planned to report for the primary end point. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change From Baseline in BMC-Z Score at Month 12 [14] | ||||||||||||||||||
End point description |
The BMC is an estimate of the amount of mineral (such as calcium) in the bone, which was assessed by DEXA scan for the posterior-anterior lumbar spine (L1_L4) and total body less head area. Positive changes from baseline indicated an improvement in condition. The safety analysis set included all randomized subjects who received at least 1 dose of study drug. Here, n (number analyzed) signifies number of subjects evaluable for this endpoint for specified category.
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End point type |
Primary
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End point timeframe |
Baseline, Month 12
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| Notes [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistical analyses was planned to report for the primary end point. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Number of Subjects with Treatment-emergent Adverse Events (TEAE) | |||||||||
End point description |
An adverse event (AE) is any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. TEAE are defined as AEs with onset during the treatment period or that are a consequence of a pre-existing condition that has worsened since baseline. Safety analysis set included all randomized subjects who received at least 1 dose of study treatment.
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End point type |
Secondary
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End point timeframe |
Up to 1 year
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| No statistical analyses for this end point | ||||||||||
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End point title |
Percentage of Subjects with Kidney Stones | ||||||||||||
End point description |
Percentage of subjects with kidney stones were reported.
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End point type |
Secondary
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End point timeframe |
Up to 1 year
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Up to Day 390
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Adverse event reporting additional description |
The safety analysis set included all randomized subjects who received at least 1 dose of study drug.
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
22.1
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Reporting groups
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Reporting group title |
Topiramate
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Reporting group description |
Subjects received topiramate weight-based sprinkle capsule and tablet, as tolerated (not to exceed 350 milligrams per day [mg/day] for subjects 2 to less than [<] 10 years of age, and not to exceed 400 mg/day for subjects 10 to 15 years of age), twice daily (BID) for up to 1 year during open-label treatment phase. Subjects were to either continue on commercially available topiramate or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Levetiracetam
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Reporting group description |
Subjects received levetiracetam weight-based tablet or oral solution, as tolerated (not to exceed 60 milligrams per kilogram per day [mg/kg/day] for subjects 2 to 15 years of age). The daily dosage was increased every 2 weeks by increments of 20 mg/kg/day to the recommended daily dosage of 60 mg/kg/day. The maximum recommended daily dosage was 3000 mg (1500 mg BID) for up to 1 year during open-label treatment phase. Subjects were to either continue on commercially available levetiracetam or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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11 Mar 2014 |
The overall reason for the amendment is to clarify exclusion and withdrawal criteria for subjects with a history of or significant risk of suicidal or violent behavior. |
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24 Aug 2017 |
The overall objective of this amendment is to improve a slower than expected study enrollment. At the current rate of subject randomization, the previously agreed upon milestone for the study completion will not be met. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Due to futility of enrollment, the study was terminated early. Also, there was no exposure to topiramate in 2 to 5 years age cohort. Therefore, no conclusions can be made with regard to this age group due to the absence of comparability. | |||
