Clinical Trial Results:
Open-label, single-arm, multicenter, pharmacokinetic, safety, and efficacy study of adjunctive administration of brivaracetam in subjects from ≥1 month to <16 years old with epilepsy
Due to a system error, the data reported in v1 is not correct and has been removed from public view.
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Summary
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EudraCT number |
2006-006536-22 |
Trial protocol |
BE CZ ES PL Outside EU/EEA |
Global end of trial date |
13 Mar 2013
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Results information
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Results version number |
v2(current) |
This version publication date |
09 Nov 2017
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First version publication date |
30 Jul 2015
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Other versions |
v1 (removed from public view) |
Version creation reason |
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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 |
N01263
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00422422 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
UCB Pharma SA
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Sponsor organisation address |
Allée de la Recherche 60, Brussels, Belgium, B-1070
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Public contact |
Clinical Trial Registries and Results Disclosure, UCB BIOSCIENCES GmbH, 0049 2173 48 15 15, clinicaltrials@ucb.com
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Scientific contact |
Clinical Trial Registries and Results Disclosure, UCB BIOSCIENCES GmbH, 0049 2173 48 15 15, clinicaltrials@ucb.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000332-PIP01-08 | ||
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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
08 May 2013
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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 |
13 Mar 2013
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objectives were to characterize the steady-state pharmacokinetics (PK) of brivaracetam (BRV) and its metabolites in subjects from ≥1 month to <16 years of age, evaluate their relationship with physiological developmental variables, and develop dosing adaptations.
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Protection of trial subjects |
Informed consent was obtained and documented in accordance with local regulations, ICH-GCP requirements, and the ethical principles that have their origin in the principles of
the Declaration of Helsinki.
Prior to obtaining informed consent, information was given in a language and at a level of complexity understandable in both oral and written form by the Investigator (or designee). Parent(s), legal representative(s), and subject if applicable had the opportunity to discuss the study and its alternatives with the Investigator.
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Background therapy |
N/A | ||
Evidence for comparator |
N/A | ||
Actual start date of recruitment |
05 Jul 2011
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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 |
Belgium: 10
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Country: Number of subjects enrolled |
Czech Republic: 5
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Country: Number of subjects enrolled |
Mexico: 19
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Country: Number of subjects enrolled |
Poland: 30
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Country: Number of subjects enrolled |
Spain: 7
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Country: Number of subjects enrolled |
United States: 29
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Worldwide total number of subjects |
100
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EEA total number of subjects |
52
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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) |
30
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Children (2-11 years) |
52
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Adolescents (12-17 years) |
18
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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 |
The N01263 study began recruitment in July 2011, with subjects enrolled in the European Union, Mexico, and the United States. The study concluded in March 2013. | ||||||||||||||||||
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Pre-assignment
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Screening details |
Participant Flow data is taken from the Enrolled Set, which is all subjects enrolled into the study. | ||||||||||||||||||
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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 |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Arm title
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Brivaracetam (ES) | ||||||||||||||||||
Arm description |
Enrolled Subjects, which is all subjects enrolled into the study. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Brivaracetam
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Investigational medicinal product code |
BRV
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Other name |
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Pharmaceutical forms |
Oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
For subjects ≥8 years:
• 0.4 mg/kg bid for Week 1
• 0.8 mg/kg bid for Week 2
• 1.6 mg/kg bid for Week 3
For subjects <8 years:
• 0.5 mg/kg bid for Week 1
• 1.0 mg/kg bid for Week 2
• 2.0 mg/kg bid for Week 3
Down-titration period (up to 2 weeks):
For subjects ≥8 years:
• 0.8 mg/kg bid for Week 4
• 0.4 mg/kg bid for Week 5
For subjects <8 years:
• 1.0 mg/kg bid for Week 4
• 0.5 mg/kg bid for Week 5
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Baseline characteristics reporting groups
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Reporting group title |
Brivaracetam (ES)
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Reporting group description |
Enrolled Subjects, which is all subjects enrolled into the study. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Brivaracetam (ES)
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Reporting group description |
Enrolled Subjects, which is all subjects enrolled into the study. | ||
Subject analysis set title |
Brivaracetam (FAS)
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Full Analysis Set, which is all subjects in the Safety Set, who have at least 1 completed post-Baseline Daily Record Card (DRC) or electroencephalogram (EEG).
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Subject analysis set title |
Brivaracetam (SS)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Safety Set, which is all enrolled subjects who took at least 1 dose of study medication. All safety analyses will be performed on the Safety Set.
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Subject analysis set title |
Brivaracetam (PPS)
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Pharmacokinetic Per Protocol Set consists of all subjects who provided at least 1 measurable plasma sample on at least 1 visit with documented drug intake times.
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End point title |
Mean Trough Plasma Concentration at 3rd Level for age range greater or equals to 1 month to less than 2 years [1] | ||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Day 21
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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: The primary objectives of study N01263 were to characterize the steady-state pharmacokinetics (PK) of brivaracetam (BRV) and its metabolites in subjects from ≥1 month to <16 years of age, evaluate their relationship with physiological developmental variables, and develop dosing adaptations. Descriptive statistics were used for the description of the PK profile of BRV across several variables. Therefore, no statistical analysis is entered. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Mean Trough Plasma Concentration at 3rd Level for age range greater or equals to 2 to less than 12 years [2] | ||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Day 21
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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: The primary objectives of study N01263 were to characterize the steady-state pharmacokinetics (PK) of brivaracetam (BRV) and its metabolites in subjects from ≥1 month to <16 years of age, evaluate their relationship with physiological developmental variables, and develop dosing adaptations. Descriptive statistics were used for the description of the PK profile of BRV across several variables. Therefore, no statistical analysis is entered. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Mean Trough Plasma Concentration at 3rd Level for age range greater or equals to 12 to less than 16 years [3] | ||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Day 21
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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: The primary objectives of study N01263 were to characterize the steady-state pharmacokinetics (PK) of brivaracetam (BRV) and its metabolites in subjects from ≥1 month to <16 years of age, evaluate their relationship with physiological developmental variables, and develop dosing adaptations. Descriptive statistics were used for the description of the PK profile of BRV across several variables. Therefore, no statistical analysis is entered. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Mean Max Plasma Concentration for age range greater or equals to 1 month to less than 2 years [4] | ||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Day 7 - 21
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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: The primary objectives of study N01263 were to characterize the steady-state pharmacokinetics (PK) of brivaracetam (BRV) and its metabolites in subjects from ≥1 month to <16 years of age, evaluate their relationship with physiological developmental variables, and develop dosing adaptations. Descriptive statistics were used for the description of the PK profile of BRV across several variables. Therefore, no statistical analysis is entered. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Mean Max Plasma Concentration for age range greater or equals to 2 to less than 12 years [5] | ||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Day 7 - 21
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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: The primary objectives of study N01263 were to characterize the steady-state pharmacokinetics (PK) of brivaracetam (BRV) and its metabolites in subjects from ≥1 month to <16 years of age, evaluate their relationship with physiological developmental variables, and develop dosing adaptations. Descriptive statistics were used for the description of the PK profile of BRV across several variables. Therefore, no statistical analysis is entered. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Mean Max Plasma Concentration for age range greater or equals to 12 to less than 16 years [6] | ||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Day 7 - 21
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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: The primary objectives of study N01263 were to characterize the steady-state pharmacokinetics (PK) of brivaracetam (BRV) and its metabolites in subjects from ≥1 month to <16 years of age, evaluate their relationship with physiological developmental variables, and develop dosing adaptations. Descriptive statistics were used for the description of the PK profile of BRV across several variables. Therefore, no statistical analysis is entered. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Number of subjects with at least one treatment-emergent adverse event reported during the 3-week evaluation period | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Baseline to end of the 3-week evaluation period
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| No statistical analyses for this end point | |||||||||
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End point title |
Percent compliance with brivaracetam oral solution during the 3-week evaluation period | ||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Baseline to the end of the 3-week evaluation period
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Number of subjects with a 50 % reduction in seizures based on seizure diary data from baseline to end of the 3-week evaluation period | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Baseline to end of the 3-week evaluation period
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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 |
Treatment-emergent Adverse Events (TEAEs) were collected during the course of the study, which started July 2011 and concluded March 2013. The Safety Set will be utilized for TEAE reporting.
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Adverse event reporting additional description |
The Safety Set is all enrolled subjects who took at least 1 dose of study drug.
Subjects had the ability to report more than one event. The Serious Adverse Events and Non-serious Adverse Events sections are reported in this manner.
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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 |
15.0
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Reporting groups
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Reporting group title |
Brivaracetam (SS)
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Reporting group description |
Safety Set, which is all enrolled subjects who took at least 1 dose of study medication. All safety analyses will be performed on the SS. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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24 Feb 2011 |
Protocol Amendment 1 (dated 24 Feb 2011) was implemented prior to the date of first patient first visit (FPFV on 05 Jul 2011). The rationale for this amendment was to update the Sponsor’s name and to add the Investigational New Drug number. Also, the Food and Drug Administration (FDA) recommendation that a PK blood sample should be taken whenever the subject reports a Serious Adverse Event (SAE) was added. |
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26 Aug 2011 |
Protocol Amendment 2 (dated 26 Aug 2011) was implemented after the date of FPFV. The rationale for this amendment was to include the Bayley Scales of Infant Development™, Second Edition (BSID-II™) in order to assess the cognitive development of pediatric subjects <18 months at Baseline in response to the European Medicines Agency’s (EMA) Paediatric Committee’s (PDCO) request. Exclusion and withdrawal criteria were extended to include the consequences of any findings related to the results of the liver function tests (LFTs). Procedures for reporting SAEs were updated to implement the FDA Final Rule requirements (Investigational new drug safety reporting requirements for human drug and biological products and safety reporting requirements for bioavailability and bioequivalence studies in humans, 21 Code of Federal Regulations [CFR] Parts 312 and 320, 2010). The Columbia-Suicide Severity Rating Scale (C-SSRS) was added to address the request of the FDA that prospective assessments for suicidality should be included in clinical studies involving all drugs for neurological indications. Some operational updates (eg, the replacement of the paper-based Case Report form [CRF] with an eCRF) were also considered. |
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15 Dec 2011 |
Protocol Amendment 3 (dated 15 Dec 2011) was implemented after the date of FPFV. The rationale for this amendment was to replace the pediatric subjects’ version of the C-SSRS with the version validated in multiple languages for subjects 6 years of age and older. The BSID-II score was replaced by the Bayley Scales of Infant and Toddler Development®, Third Edition (Bayley-III®) scales in order to apply the most recent version of the cognition scale; no data were collected using the BSID-II before this change was implemented. In addition, it was clarified that the cognition scale would be used only in English-speaking countries, since it was validated only in English. The requirements for blood sampling (volumes and frequencies of the blood samples) were updated based on the subject’s body weight and all sections referring to biochemistry assessments were amended in order to clarify that tests for hepatic monitoring were to be included in all safety laboratory assessments. Furthermore, an error in the mathematical symbols used for the presentation of the age limits of the EEG assessments was corrected, and the SAE reporting details were updated. Administrative changes included the update of the Clinical Project Manager contact details and typographical corrections. |
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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. | |||
| None reported | |||
