Clinical Trial Results:
A multi-center, open-label, four-arm, randomized trial evaluating the safety and tolerability of Brivaracetam intravenous infusion and bolus, administered in BID regimen as an adjunctive antiepileptic treatment in subjects from 16 to 70 years suffering from epilepsy
Summary
|
|
EudraCT number |
2008-004714-27 |
Trial protocol |
CZ DE |
Global end of trial date |
20 Jul 2012
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
02 Apr 2016
|
First version publication date |
02 Apr 2016
|
Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
N01258
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01405508 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
UCB Biosciences Inc.
|
||
Sponsor organisation address |
8010 Arco Corporate Drive, Raleigh, United States, NC 27617
|
||
Public contact |
Clinical Trial Registries and Results Disclosure, UCB BIOSCIENCES GmbH, +49 2173 4815 15, clinicaltrials@ucb.com
|
||
Scientific contact |
Clinical Trial Registries and Results Disclosure, UCB BIOSCIENCES GmbH, +49 2173 48 15 15, clinicaltrials@ucb.com
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
26 Sep 2012
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
20 Jul 2012
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
The primary objective was to evaluate the safety and tolerability of Brivaracetam (BRV) 200 mg/day administered intravenous (iv) as an infusion or a bolus, according to an initiation or a conversion scheme, during repeated dosing (100 mg/Administration twice a day (bid) for 4.5 days) as an adjunctive treatment in adult subjects suffering from localization-related or generalized epilepsy.
|
||
Protection of trial subjects |
Standard measures to minimize pain and distress.
|
||
Background therapy |
Not applicable | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
09 Aug 2011
|
||
Long term follow-up planned |
Yes
|
||
Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
5 Years | ||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
United States: 74
|
||
Country: Number of subjects enrolled |
Czech Republic: 8
|
||
Country: Number of subjects enrolled |
Germany: 7
|
||
Country: Number of subjects enrolled |
Poland: 16
|
||
Worldwide total number of subjects |
105
|
||
EEA total number of subjects |
31
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
103
|
||
From 65 to 84 years |
2
|
||
85 years and over |
0
|
|
||||||||||||||||||||||||||
Recruitment
|
||||||||||||||||||||||||||
Recruitment details |
This study started to recruit patients in August 2011 and concluded in July 2012. 105 subjects were randomized to 4 different treatment groups. | |||||||||||||||||||||||||
Pre-assignment
|
||||||||||||||||||||||||||
Screening details |
Participant Flow refers to the Randomized Set (RS). | |||||||||||||||||||||||||
Period 1
|
||||||||||||||||||||||||||
Period 1 title |
Study Overall (overall period)
|
|||||||||||||||||||||||||
Is this the baseline period? |
Yes | |||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
|||||||||||||||||||||||||
Blinding used |
Not blinded | |||||||||||||||||||||||||
Arms
|
||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||||||
Arm title
|
Placebo tablets / Brivaracetam bolus | |||||||||||||||||||||||||
Arm description |
Subjects will receive Placebo (PBO) tablets for one week followed by Brivaracetam (BRV) bolus for 4.5 days. Down-Titration: - If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In - If subject discontinues during the Evaluation Period or after Day 12, the subject will receive Placebo tablets during Down-Titration: Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
|
|||||||||||||||||||||||||
Investigational medicinal product code |
PBO
|
|||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Film-coated tablet
|
|||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||
Dosage and administration details |
100 mg twice daily (BID) for 7 days during Run-In Period.
|
|||||||||||||||||||||||||
Investigational medicinal product name |
Brivaracetam bolus
|
|||||||||||||||||||||||||
Investigational medicinal product code |
BRV bolus
|
|||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Infusion
|
|||||||||||||||||||||||||
Routes of administration |
Intravenous bolus use
|
|||||||||||||||||||||||||
Dosage and administration details |
10 mL (= 100 mg) of Brivaracetam administered intravenously over 2 minutes twice daily (BID) during Evaluation Period.
|
|||||||||||||||||||||||||
Arm title
|
Placebo tablets / Brivaracetam infusion | |||||||||||||||||||||||||
Arm description |
Subjects will receive Placebo (PBO) tablets for one week followed by Brivaracetam (BRV) intravenous infusion for 4.5 days. Down-Titration: - If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In - If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration: Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
|
|||||||||||||||||||||||||
Investigational medicinal product code |
PBO
|
|||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Film-coated tablet
|
|||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||
Dosage and administration details |
100 mg twice daily (BID) for 7 days during Run-In Period.
|
|||||||||||||||||||||||||
Investigational medicinal product name |
Brivaracetam infusion
|
|||||||||||||||||||||||||
Investigational medicinal product code |
BRV infusion
|
|||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Infusion
|
|||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
|||||||||||||||||||||||||
Dosage and administration details |
10 mL (= 100 mg) of Brivaracetam diluted in 90 mL 0.9 % isotonic saline sterile solution for intravenous administration infused over 15 minutes twice daily (BID) during Evaluation Period.
|
|||||||||||||||||||||||||
Arm title
|
Brivaracetam (BRV) tablets / BRV bolus | |||||||||||||||||||||||||
Arm description |
Subjects will receive Brivaracetam (BRV) tablets for one week followed by BRV bolus for 4.5 days. Down-Titration: - If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In - If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration: Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake bid for the fourth week | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
Brivaracetam tablets
|
|||||||||||||||||||||||||
Investigational medicinal product code |
BRV tablets
|
|||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Film-coated tablet
|
|||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||
Dosage and administration details |
100 mg, intake twice daily (BID) for 7 days during Run-In Period.
|
|||||||||||||||||||||||||
Investigational medicinal product name |
Brivaracetam bolus
|
|||||||||||||||||||||||||
Investigational medicinal product code |
BRV bolus
|
|||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Infusion
|
|||||||||||||||||||||||||
Routes of administration |
Intravenous bolus use
|
|||||||||||||||||||||||||
Dosage and administration details |
10 mL (= 100 mg) of Brivaracetam administered intravenously over 2 minutes twice daily (BID) during Evaluation Period.
|
|||||||||||||||||||||||||
Arm title
|
Brivaracetam (BRV) tablets / BRV infusion | |||||||||||||||||||||||||
Arm description |
Subjects will receive Brivaracetam (BRV) tablets for one week followed by Brivaracetam intravenous infusion for 4.5 days. Down-Titration: - If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In - If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration: Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
Brivaracetam tablets
|
|||||||||||||||||||||||||
Investigational medicinal product code |
BRV tablets
|
|||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Film-coated tablet
|
|||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||
Dosage and administration details |
100 mg, intake twice daily (BID) for 7 days during Run-In Period.
|
|||||||||||||||||||||||||
Investigational medicinal product name |
Brivaracetam infusion
|
|||||||||||||||||||||||||
Investigational medicinal product code |
BRV infusion
|
|||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Infusion
|
|||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
|||||||||||||||||||||||||
Dosage and administration details |
10 mL (= 100 mg) of Brivaracetam diluted in 90 mL 0.9 % isotonic saline sterile solution for intravenous administration infused over 15 minutes twice daily (BID) during Evaluation Period.
|
|||||||||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo tablets / Brivaracetam bolus
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects will receive Placebo (PBO) tablets for one week followed by Brivaracetam (BRV) bolus for 4.5 days. Down-Titration: - If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In - If subject discontinues during the Evaluation Period or after Day 12, the subject will receive Placebo tablets during Down-Titration: Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo tablets / Brivaracetam infusion
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects will receive Placebo (PBO) tablets for one week followed by Brivaracetam (BRV) intravenous infusion for 4.5 days. Down-Titration: - If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In - If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration: Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Brivaracetam (BRV) tablets / BRV bolus
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects will receive Brivaracetam (BRV) tablets for one week followed by BRV bolus for 4.5 days. Down-Titration: - If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In - If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration: Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake bid for the fourth week | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Brivaracetam (BRV) tablets / BRV infusion
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects will receive Brivaracetam (BRV) tablets for one week followed by Brivaracetam intravenous infusion for 4.5 days. Down-Titration: - If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In - If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration: Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Placebo tablets / Brivaracetam bolus
|
||
Reporting group description |
Subjects will receive Placebo (PBO) tablets for one week followed by Brivaracetam (BRV) bolus for 4.5 days. Down-Titration: - If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In - If subject discontinues during the Evaluation Period or after Day 12, the subject will receive Placebo tablets during Down-Titration: Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week | ||
Reporting group title |
Placebo tablets / Brivaracetam infusion
|
||
Reporting group description |
Subjects will receive Placebo (PBO) tablets for one week followed by Brivaracetam (BRV) intravenous infusion for 4.5 days. Down-Titration: - If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In - If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration: Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week | ||
Reporting group title |
Brivaracetam (BRV) tablets / BRV bolus
|
||
Reporting group description |
Subjects will receive Brivaracetam (BRV) tablets for one week followed by BRV bolus for 4.5 days. Down-Titration: - If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In - If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration: Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake bid for the fourth week | ||
Reporting group title |
Brivaracetam (BRV) tablets / BRV infusion
|
||
Reporting group description |
Subjects will receive Brivaracetam (BRV) tablets for one week followed by Brivaracetam intravenous infusion for 4.5 days. Down-Titration: - If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In - If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration: Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week |
|
|||||||||||||||||||||
End point title |
Number of subjects with at least one treatment-emergent adverse event during the study (maximum 40 days) [1] | ||||||||||||||||||||
End point description |
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
40 days
|
||||||||||||||||||||
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 formal statistical hypothesis testing was planned for this study. Results were summarized in tables as descriptive statistics only. |
|||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Number of subjects who withdrew due to a treatment-emergent adverse event during the study (maximum 40 days) | ||||||||||||||||||||
End point description |
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
40 days
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Number of subjects with at least one injection-related treatment-emergent adverse event (TEAE) during the Evaluation Period. | ||||||||||||||||||||
End point description |
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
4.5-day Evaluation Period
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Adverse Events were collected from Baseline over Run-In (Day 1) and Evaluation Period (Day 8 to Day 12) to the Safety Visit or Early Discontinuation Visit (up to 54 days).
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Adverse Events refer to the Safety Population consisting of all subjects who took at least 1 dose of study drug.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
15.0
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo tablets / Brivaracetam bolus
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects will receive Placebo (PBO) tablets for one week followed by Brivaracetam (BRV) bolus for 4.5 days. Down-Titration: o If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In o If subject discontinues during the Evaluation Period or after Day 12, the subject will receive Placebo tablets during Down-Titration: Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Brivaracetam (BRV) tablets / BRV bolus
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects will receive Brivaracetam (BRV) tablets for one week followed by BRV bolus for 4.5 days. Down-Titration: o If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In o If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration: Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake bid for the fourth week | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Brivaracetam (BRV) tablets / BRV infusion
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects will receive Brivaracetam (BRV) tablets for one week followed by Brivaracetam intravenous infusion for 4.5 days. Down-Titration: o If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In o If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration: Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo tablets / Brivaracetam infusion
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects will receive Placebo (PBO) tablets for one week followed by Brivaracetam (BRV) intravenous infusion for 4.5 days. Down-Titration: o If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In o If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration: Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
08 Dec 2008 |
Protocol Amendment 1 was approved and effective prior to the date of first patient first visit (FPFV). The rationale for this amendment was to integrate the USA Food and Drug Administration (FDA) recommendations regarding cardiac monitoring, received on 20 Nov 2008:
- At V2, an ECG was added
- Immediately after each BRV iv administration, ECGs were added
- A central reader was organized for the ECG tracings
- The section describing the adverse events (AEs) was updated to be consistent with the new CRF AE module
- The recently defined IND number for BRV iv development was implemented |
||
05 Mar 2009 |
Protocol Amendment 2 was approved and effective prior to the date of FPFV. The rationale for this amendment was to integrate the USA FDA recommendations regarding cardiac monitoring, as expressed in their letter received on 19 Feb 2009, in response to the Investigational New Drug
(IND) submission for BRV iv solution:
- 12-lead ECGs were to be recorded; predose and at 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 12 hours immediately after the initiation of BRV iv administration
- During the BRV iv administration, continuous live monitoring of ECG was included
- There was a change in the statistical analysis of the ECG data, with only the central readings of the ECG data to be used in the descriptive and shift tables |
||
01 Apr 2011 |
Protocol Amendment 3 was approved and effective prior to the date of FPFV. The rationale for this amendment was to increase the total daily dose of BRV to 200 mg/day (100 mg/intake bid) from the original dose of 100 mg/day (50 mg/intake bid) in line with the recommendation of the regulatory authorities and in accordance with the oral dose that UCB had selected for Evaluation in the new Phase 3 study (N01358).
The following changes were made throughout the protocol:
- The dose in the LTFU study (N01379) was increased from 100 mg/day to 200 mg/day
- The Down-Titration Period was increased from 2 weeks to 4 weeks with a 4-step down-titration instead of the previous 2-step down-titration
- The dosing schedule for the Down-Titration Period was clarified
- The duration of the iv bolus was increased from 60 seconds to 2 minutes
- The maximum study and treatment durations for each subject were increased
- The number of sites expected to participate in the study was increased to approximately 35
- Information on blinding during the Run-In Period and the Down-Titration Period was added
- Information on the description of the study drug, packaging, and supply was updated
- The timing of serum and urine pregnancy tests was revised
- The randomization and IVRS processes was updated |
||
01 Apr 2011 |
The following changes were made throughout the protocol:
- The patient-reported outcomes (PRO) questionnaires (Patient Weighted Quality of Life in Epilepsy Inventory-Form 31 [QOLIE-31-P] and Hospital Anxiety and Depression Scale [HADS]) were removed from the exploratory objectives and variables. Only baseline data were collected at V2 to allow for evaluation later in the LTFU study, N01379
- The EuroQoL-5 Dimensions questionnaire was removed
- Socio-professional data were added at V2 to provide baseline data to allow for eEvaluation later in the LTFU study, N01379
- The collection and analysis of deoxyribonucleic acid (DNA) samples were removed, as this analysis will be conducted in another study
- The exploratory objective for healthcare resource utilization was corrected to include this assessment at other visits as well as baseline data
- The number of the LTFU study was added
- The timing of the BRV and AED sampling during the iv administration was revised, and the sampling of concomitant AED levels at the SV (V8) was removed
- Healthcare provider consultations not foreseen by the protocol was added as a component of the healthcare resource utilization variable
- The Sponsor contact information was updated
- The contract research organization (CRO) information was added
- The protocol summary and introduction sections were updated
- Other minor editorial changes were made to ensure consistency within the protocol and across the BRV program |
||
12 Sep 2011 |
Protocol Amendment 4 was approved and effective after subjects had been enrolled in the study. The rationale for this amendment was to implement the USA FDA Final Rule requirements with regard to procedures for reporting serious adverse events (SAEs) and to address the requirement of the FDA that prospective assessments for suicidality should be included in clinical studies involving all drugs for neurological indications.
The following changes were made throughout the protocol:
- A suicidality assessment using the Columbia-Suicide Severity Rating Scale (C-SSRS) in response to the USA FDA requirement was included
- The prospective assessment for suicidality using the C-SSRS was added to the exclusion criteria, withdrawal criteria, and safety assessments
- The list of Anticipated SAEs in response to the USA FDA Final Rule was added
- A few minor changes were made to the protocol to update the name of the Clinical Project Manager (CPM), to clarify some study conduct details, and to correct grammatical errors |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |