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Trial record 1 of 3 for:    NCT00490035
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Double-blind, Randomized Study Evaluating the Efficacy and Safety of Brivaracetam in Adults With Partial Onset Seizures

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ClinicalTrials.gov Identifier: NCT00490035
Recruitment Status : Completed
First Posted : June 22, 2007
Results First Posted : April 13, 2016
Last Update Posted : August 31, 2020
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( UCB Pharma SA )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Epilepsy
Interventions Other: Placebo
Drug: Brivaracetam
Enrollment 399
Recruitment Details This study started to enroll subjects in September 2007 and concluded in February 2009.
Pre-assignment Details Participant Flow refers to the Randomized Set.
Arm/Group Title Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Hide Arm/Group Description Matching Placebo tablets administered twice a day Brivaracetam 20 mg/day, 10 mg administered twice a day Brivaracetam 50 mg/day, 25 mg administered twice a day Brivaracetam 100 mg/day, 50 mg administered twice a day
Period Title: Overall Study
Started 100 99 100 100
Completed 92 93 88 94
Not Completed 8 6 12 6
Reason Not Completed
AE, non-serious non-fatal             3             4             4             5
Lost to Follow-up             2             0             1             0
Withdrawal by Subject             2             1             1             0
Other reason             0             1             3             1
AE, serious fatal             1             0             0             0
Serious adverse event (SAE), non-fatal             0             0             1             0
AE of unknown type             0             0             2             0
Arm/Group Title Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day Total Title
Hide Arm/Group Description Matching Placebo tablets administered twice a day Brivaracetam 20 mg/day, 10 mg administered twice a day Brivaracetam 50 mg/day, 25 mg administered twice a day Brivaracetam 100 mg/day, 50 mg administered twice a day [Not Specified]
Overall Number of Baseline Participants 100 99 100 100 399
Hide Baseline Analysis Population Description
Baseline Characteristics refer to the Randomized Set.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 100 participants 99 participants 100 participants 100 participants 399 participants
36.4  (13.0) 35.7  (12.5) 39.0  (13.5) 38.0  (13.1) 37.24  (13.05)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 100 participants 99 participants 100 participants 100 participants 399 participants
<18 years 2 2 0 1 5
Between 18 and 65 years 96 94 97 96 383
>=65 years 2 3 3 3 11
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 100 participants 99 participants 100 participants 100 participants 399 participants
Female
46
  46.0%
38
  38.4%
45
  45.0%
42
  42.0%
171
  42.9%
Male
54
  54.0%
61
  61.6%
55
  55.0%
58
  58.0%
228
  57.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 100 participants 99 participants 100 participants 100 participants 399 participants
Hungary 4 2 3 3 12
Poland 26 28 27 27 108
India 23 22 23 23 91
Belgium 3 0 3 0 6
Finland 3 3 1 4 11
France 17 17 11 15 60
Germany 8 10 14 9 41
Italy 4 8 3 5 20
Netherlands 3 0 1 3 7
Spain 8 4 6 4 22
Switzerland 1 3 6 5 15
United Kingdom 0 2 2 2 6
1.Primary Outcome
Title Partial Onset Seizure (Type I) Frequency Per Week Over the 12-week Treatment Period
Hide Description Partial (Type I) Seizures can be classified into one of the following three groups: Simple Partial Seizures, Complex Partial Seizures, Partial Seizures evolving to Secondarily Generalized Seizures.
Time Frame From Baseline to 12-week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
The Intention-to-treat (ITT) population was defined as all randomized subjects who received at least 1 dose of study medication.
Arm/Group Title Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Hide Arm/Group Description:
Matching Placebo tablets administered twice a day
Brivaracetam 20 mg/day, 10 mg administered twice a day
Brivaracetam 50 mg/day, 25 mg administered twice a day
Brivaracetam 100 mg/day, 50 mg administered twice a day
Overall Number of Participants Analyzed 100 99 99 100
Median (Inter-Quartile Range)
Unit of Measure: Seizure Frequency per Week
1.75
(0.76 to 5.12)
1.34
(0.70 to 3.12)
1.49
(0.69 to 2.78)
1.26
(0.52 to 2.93)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Brivaracetam 50 mg/Day
Comments In order to control the Type I error testing was performed in sequence starting with 50 mg, then 100 mg and finally 20 mg Brivaracetam per day versus Placebo, only moving to the next test if the previous one was significant at the 5 % level.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.261
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Reduction over Placebo
Estimated Value 6.5
Confidence Interval (2-Sided) 95%
-5.2 to 16.9
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Responder Rate for Partial Onset Seizures (Type I) Frequency Per Week Over the 12-week Treatment Period
Hide Description

Responders are those subjects with at least 50 % reduction from Baseline to Treatment Period in Partial Onset Seizure frequency per week.

The Responder Rate for Partial Onset Seizures (Type I) is the proportion of subjects who have a >= 50 % reduction in seizure frequency per week from Baseline.
Time Frame From Baseline to 12-week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
The Intention-to-treat (ITT) population was defined as all randomized subjects who received at least 1 dose of study medication.
Arm/Group Title Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Hide Arm/Group Description:
Matching Placebo tablets administered twice a day
Brivaracetam 20 mg/day, 10 mg administered twice a day
Brivaracetam 50 mg/day, 25 mg administered twice a day
Brivaracetam 100 mg/day, 50 mg administered twice a day
Overall Number of Participants Analyzed 100 99 99 100
Measure Type: Number
Unit of Measure: Percentage of Participants
Non-responders 80.0 72.7 72.7 64.0
Responders 20.0 27.3 27.3 36.0
3.Secondary Outcome
Title All Seizure Frequency (Type I+II+III) Per Week Over the 12-week Treatment Period
Hide Description There are three types of Epilepsy: Partial Epilepsies (Type I), Generalized Epilepsies (Type II) and uncertain classification of Epilepsies (Type III).
Time Frame From Baseline to 12-week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
The Intention-to-treat (ITT) population was defined as all randomized subjects who received at least 1 dose of study medication.
Arm/Group Title Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Hide Arm/Group Description:
Matching Placebo tablets administered twice a day
Brivaracetam 20 mg/day, 10 mg administered twice a day
Brivaracetam 50 mg/day, 25 mg administered twice a day
Brivaracetam 100 mg/day, 50 mg administered twice a day
Overall Number of Participants Analyzed 100 99 99 100
Median (Inter-Quartile Range)
Unit of Measure: Times per week
1.75
(0.76 to 5.61)
1.34
(0.70 to 3.12)
1.49
(0.69 to 2.78)
1.26
(0.52 to 2.93)
4.Secondary Outcome
Title Percent Change From Baseline to the 12-week Treatment Period in Partial Onset Seizure (Type I) Frequency Per Week
Hide Description The percent change from Baseline was computed as: Weekly Seizure Frequency (Treatment) - Weekly Seizure Frequency (Baseline) / Weekly Seizure Frequency (Baseline) * 100. Negative values indicate a reduction from Baseline with higher negative values showing higher reduction.
Time Frame From Baseline to 12-week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
The Intention-to-treat (ITT) population was defined as all randomized subjects who received at least 1 dose of study medication.
Arm/Group Title Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Hide Arm/Group Description:
Matching Placebo tablets administered twice a day
Brivaracetam 20 mg/day, 10 mg administered twice a day
Brivaracetam 50 mg/day, 25 mg administered twice a day
Brivaracetam 100 mg/day, 50 mg administered twice a day
Overall Number of Participants Analyzed 100 99 99 100
Median (Inter-Quartile Range)
Unit of Measure: Percent change in seizures per week
-17.03
(-40.27 to 17.59)
-30.03
(-55.99 to -2.11)
-26.83
(-60.05 to 6.32)
-32.45
(-72.51 to 0.04)
5.Secondary Outcome
Title Categorized Percentage Change From Baseline in Seizure Frequency for Partial Onset Seizure (Type I) Over the 12-week Treatment Period
Hide Description

The categories are:

  • <= 25 %
  • - 25 % to < 25 %
  • 25 % to < 50 %
  • 50 % to < 75 %
  • 75 % to < 100 %
  • 100 %
Time Frame From Baseline to 12-week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
The Intention-to-treat (ITT) population was defined as all randomized subjects who received at least 1 dose of study medication.
Arm/Group Title Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Hide Arm/Group Description:
Matching Placebo tablets administered twice a day
Brivaracetam 20 mg/day, 10 mg administered twice a day
Brivaracetam 50 mg/day, 25 mg administered twice a day
Brivaracetam 100 mg/day, 50 mg administered twice a day
Overall Number of Participants Analyzed 100 99 99 100
Measure Type: Number
Unit of Measure: Percentage of Participants
<= 25 % 19.0 10.1 15.2 10.0
- 25 % to < 25 % 41.0 35.4 33.3 33.0
25 % to < 50 % 20.0 27.3 24.2 21.0
50 % to < 75 % 12.0 18.2 17.2 14.0
75 % to < 100 % 8.0 7.1 9.1 18.0
100 % 0 2.0 1.0 4.0
6.Secondary Outcome
Title Seizure Freedom Rate (All Seizure Types) Over the 12-week Treatment Period
Hide Description Subjects were considered seizure free if their seizure counts for every day over the entire Treatment Period was zero and if they completed the Treatment Period.
Time Frame From Baseline to 12-week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
The Intention-to-treat (ITT) population was defined as all randomized subjects who received at least 1 dose of study medication.
Arm/Group Title Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Hide Arm/Group Description:
Matching Placebo tablets administered twice a day
Brivaracetam 20 mg/day, 10 mg administered twice a day
Brivaracetam 50 mg/day, 25 mg administered twice a day
Brivaracetam 100 mg/day, 50 mg administered twice a day
Overall Number of Participants Analyzed 100 99 99 100
Measure Type: Number
Unit of Measure: Percentage of Participants
Seizure free 0 2.0 0 4.0
No Seizures but non-completer 0 0 1.0 0
Not Seizure-free 100.0 98.0 99.0 96.0
7.Secondary Outcome
Title Time to First Type I Seizure During the 12-week Treatment Period
Hide Description The time to first Type I Seizure during the 12-week Treatment Period was measured in days.
Time Frame From Baseline to 12-week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
The Intention-to-treat (ITT) population was defined as all randomized subjects who received at least 1 dose of study medication.
Arm/Group Title Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Hide Arm/Group Description:
Matching Placebo tablets administered twice a day
Brivaracetam 20 mg/day, 10 mg administered twice a day
Brivaracetam 50 mg/day, 25 mg administered twice a day
Brivaracetam 100 mg/day, 50 mg administered twice a day
Overall Number of Participants Analyzed 100 99 99 100
Median (95% Confidence Interval)
Unit of Measure: Days
4
(3 to 5)
6
(3 to 8)
6
(4 to 10)
4
(3 to 5)
8.Secondary Outcome
Title Time to Fifth Type I Seizure During the 12-week Treatment Period
Hide Description The time to Fifth Type I Seizure during the 12-week Treatment Period was measured in days.
Time Frame From Baseline to 12-week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
The Intention-to-treat (ITT) population was defined as all randomized subjects who received at least 1 dose of study medication.
Arm/Group Title Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Hide Arm/Group Description:
Matching Placebo tablets administered twice a day
Brivaracetam 20 mg/day, 10 mg administered twice a day
Brivaracetam 50 mg/day, 25 mg administered twice a day
Brivaracetam 100 mg/day, 50 mg administered twice a day
Overall Number of Participants Analyzed 100 99 99 100
Median (95% Confidence Interval)
Unit of Measure: Days
19
(14 to 25)
25
(20 to 34)
24
(20 to 32)
24
(18 to 34)
9.Secondary Outcome
Title Time to Tenth Type I Seizure During the 12-week Treatment Period
Hide Description The time to tenth Type I Seizure during the 12-week Treatment Period was measured in days.
Time Frame From Baseline to 12-week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
The Intention-to-treat (ITT) population was defined as all randomized subjects who received at least 1 dose of study medication.
Arm/Group Title Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Hide Arm/Group Description:
Matching Placebo tablets administered twice a day
Brivaracetam 20 mg/day, 10 mg administered twice a day
Brivaracetam 50 mg/day, 25 mg administered twice a day
Brivaracetam 100 mg/day, 50 mg administered twice a day
Overall Number of Participants Analyzed 100 99 99 100
Median (95% Confidence Interval)
Unit of Measure: Days
39
(24 to 50)
49
(36 to 64)
40
(33 to 49)
46
(34 to 66)
10.Secondary Outcome
Title Reduction of Type IC/Type I Seizure Frequency Ratio From Baseline to the 12- Week Treatment Period.
Hide Description The type IC/Type I seizure frequency ratio is represented by the percentage of subjects having a reduction in the ratio of Type IC seizure frequency over Type IA, IB, and IC seizure frequency from Baseline to Treatment Period.
Time Frame From Baseline to 12-week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description

The Intention-to-treat (ITT) population was defined as all randomized subjects who received at least 1 dose of study medication.

Type IC Population consists of those subjects with at least one Type IC seizure during the Baseline period.
Arm/Group Title Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Hide Arm/Group Description:
Matching Placebo tablets administered twice a day
Brivaracetam 20 mg/day, 10 mg administered twice a day
Brivaracetam 50 mg/day, 25 mg administered twice a day
Brivaracetam 100 mg/day, 50 mg administered twice a day
Overall Number of Participants Analyzed 37 36 40 39
Measure Type: Number
Unit of Measure: percentage of participants
45.9 47.2 62.5 41.0
11.Secondary Outcome
Title Change From Baseline to the 12-week Treatment Period in Total Patient Weighted Quality of Life in Epilepsy Inventory-Form 31 (QOLIE-31-P) Score
Hide Description The QOLIE-31-P is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into seven multi-item subscales - Seizure Worry (5 items), Overall Quality of Life (2 items), Emotional Well-Being (5 items), Energy/Fatigue (4 items), Cognitive Functioning (6 items), Medication Effects (3 items) and Daily Activities/Social Functioning (5 items) - and a Health Status item. The subscale scores, the Total score and the Health Status item score are calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100 and higher scores indicating better function. A positive value in Change from Baseline indicates an improvement from Baseline.
Time Frame From Baseline to 12-week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects in the Intention-To-Treat (ITT) population with measurements at Baseline and Last Visit / Early Discontinuation.
Arm/Group Title Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Hide Arm/Group Description:
Matching Placebo tablets administered twice a day
Brivaracetam 20 mg/day, 10 mg administered twice a day
Brivaracetam 50 mg/day, 25 mg administered twice a day
Brivaracetam 100 mg/day, 50 mg administered twice a day
Overall Number of Participants Analyzed 86 91 94 80
Mean (Standard Deviation)
Unit of Measure: units on a scale
2.29  (14.03) 4.50  (12.71) 3.09  (14.43) 1.78  (13.95)
12.Secondary Outcome
Title Change From Baseline to the 12-week Treatment Period in Seizure Worry Patient Weighted Quality of Life in Epilepsy Inventory-Form 31 (QOLIE-31-P) Score
Hide Description The QOLIE-31-P is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into seven multi-item subscales - Seizure Worry (5 items), Overall Quality of Life (2 items), Emotional Well-Being (5 items), Energy/Fatigue (4 items), Cognitive Functioning (6 items), Medication Effects (3 items) and Daily Activities/Social Functioning (5 items) - and a Health Status item. The subscale scores, the Total score and the Health Status item score are calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100 and higher scores indicating better function. A positive value in Change from Baseline indicates an improvement from Baseline.
Time Frame From Baseline to 12-week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects in the Intention-To-Treat (ITT) population with measurements at Baseline and Last Visit / Early Discontinuation.
Arm/Group Title Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Hide Arm/Group Description:
Matching Placebo tablets administered twice a day
Brivaracetam 20 mg/day, 10 mg administered twice a day
Brivaracetam 50 mg/day, 25 mg administered twice a day
Brivaracetam 100 mg/day, 50 mg administered twice a day
Overall Number of Participants Analyzed 88 93 96 86
Mean (Standard Deviation)
Unit of Measure: units on a scale
8.25  (22.01) 6.23  (17.97) 5.34  (23.81) 8.04  (26.26)
13.Secondary Outcome
Title Change From Baseline to the 12-week Treatment Period in Daily Activities/Social Functioning Patient Weighted Quality of Life in Epilepsy Inventory-Form 31 (QOLIE-31-P) Score
Hide Description The QOLIE-31-P is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into seven multi-item subscales - Seizure Worry (5 items), Overall Quality of Life (2 items), Emotional Well-Being (5 items), Energy/Fatigue (4 items), Cognitive Functioning (6 items), Medication Effects (3 items) and Daily Activities/Social Functioning (5 items) - and a Health Status item. The subscale scores, the Total score and the Health Status item score are calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100 and higher scores indicating better function. A positive value in Change from Baseline indicates an improvement from Baseline.
Time Frame From Baseline to 12-week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects in the Intention-to-treat (ITT) population with measurements at Baseline and Last Visit / Early Discontinuation.
Arm/Group Title Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Hide Arm/Group Description:
Matching Placebo tablets administered twice a day
Brivaracetam 20 mg/day, 10 mg administered twice a day
Brivaracetam 50 mg/day, 25 mg administered twice a day
Brivaracetam 100 mg/day, 50 mg administered twice a day
Overall Number of Participants Analyzed 88 93 96 85
Mean (Standard Deviation)
Unit of Measure: units on a scale
-2.09  (20.26) 3.35  (19.72) 3.09  (20.79) 3.50  (22.52)
14.Secondary Outcome
Title Change From Baseline to the 12-week Treatment Period in Hospital Anxiety Score
Hide Description The Hospital Anxiety and Depression Scale (HADS) was used to evaluate anxiety and depression simultaneously. The HADS was developed as a self-administered scale that has been designed to assess the presence and severity of both anxiety and depression. It consists of 14 items that are scored on a 4-point severity scale ranging from 0 to 3. A score per dimension was calculated with each score ranging from 0 to 21 and higher scores indicating higher depression / anxiety. Negative values in Change from Baseline indicate a decrease of HADS from Baseline to Treatment Period.
Time Frame From Baseline to 12-week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects in the Intention-to-treat (ITT) population with measurements at Baseline and Last Visit / Early Discontinuation.
Arm/Group Title Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Hide Arm/Group Description:
Matching Placebo tablets administered twice a day
Brivaracetam 20 mg/day, 10 mg administered twice a day
Brivaracetam 50 mg/day, 25 mg administered twice a day
Brivaracetam 100 mg/day, 50 mg administered twice a day
Overall Number of Participants Analyzed 86 91 95 83
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.54  (3.89) -0.59  (3.89) -0.41  (3.82) 0.08  (3.60)
15.Secondary Outcome
Title Change From Baseline to the 12-week Treatment Period in Hospital Depression Score
Hide Description The Hospital Anxiety and Depression Scale (HADS) was used to evaluate anxiety and depression simultaneously. The HADS was developed as a self-administered scale that has been designed to assess the presence and severity of both anxiety and depression. It consists of 14 items that are scored on a 4-point severity scale ranging from 0 to 3. A score per dimension was calculated with each score ranging from 0 to 21 and higher scores indicating higher depression / anxiety. Negative values in Change from Baseline indicate a decrease of HADS from Baseline to Treatment Period.
Time Frame From Baseline to 12-week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects in the Intention-to-treat (ITT) population with measurements at Baseline and Last Visit / Early Discontinuation Visit.
Arm/Group Title Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Hide Arm/Group Description:
Matching Placebo tablets administered twice a day
Brivaracetam 20 mg/day, 10 mg administered twice a day
Brivaracetam 50 mg/day, 25 mg administered twice a day
Brivaracetam 100 mg/day, 50 mg administered twice a day
Overall Number of Participants Analyzed 86 91 95 83
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.65  (3.58) -0.10  (3.67) 0.26  (3.84) -0.24  (3.69)
16.Secondary Outcome
Title Patient's Global Evaluation Scale (P-GES) Evaluated at Last Visit or Early Discontinuation Visit
Hide Description The Patient's Global Evaluation Scale (P-GES) is a global assessment of the disease evolution which was performed using a seven-point scale (1 = Marked worsening to 7 = Marked improvement) with the start of the study medication as the reference time point. The subject not mentally impaired had to complete it by answering the following question: "Overall, has there been a change in your seizures since the start of the study medication?"
Time Frame Last Visit or Early Discontinuation Visit in the 12-week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects in the Intention-to-treat (ITT) population with measurements at Baseline and Last Visit or Early Discontinuation Visit.
Arm/Group Title Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Hide Arm/Group Description:
Matching Placebo tablets administered twice a day
Brivaracetam 20 mg/day, 10 mg administered twice a day
Brivaracetam 50 mg/day, 25 mg administered twice a day
Brivaracetam 100 mg/day, 50 mg administered twice a day
Overall Number of Participants Analyzed 81 90 90 85
Mean (Standard Deviation)
Unit of Measure: units on a scale
4.93  (1.39) 5.17  (1.27) 5.04  (1.29) 5.47  (1.16)
17.Secondary Outcome
Title Investigator's Global Evaluation Scale (I-GES) Evaluated at Last Visit or Early Discontinuation Visit
Hide Description The Investigator's Global Evaluation Scale (I-GES) is a global assessment of the disease evolution which was performed using a seven-point scale (1 = Marked worsening to 7 = Marked improvement), with the start of the study medication as reference time point. The Investigator was to complete it by answering the following question: "Assess the Overall change in the severity of patient's illness, compared to start of study medication."
Time Frame Last Visit or Early Discontinuation Visit in the 12-week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects in the Intention-to-treat (ITT) population with measurements at Baseline and Last Visit or Early Discontinuation Visit.
Arm/Group Title Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Hide Arm/Group Description:
Matching Placebo tablets administered twice a day
Brivaracetam 20 mg/day, 10 mg administered twice a day
Brivaracetam 50 mg/day, 25 mg administered twice a day
Brivaracetam 100 mg/day, 50 mg administered twice a day
Overall Number of Participants Analyzed 96 99 98 100
Mean (Standard Deviation)
Unit of Measure: units on a scale
4.78  (1.20) 4.99  (1.15) 4.99  (1.10) 5.34  (1.12)
18.Secondary Outcome
Title Change From Baseline to the 12-week Treatment Period in Energy/Fatigue Patient Weighted Quality of Life in Epilepsy Inventory-Form 31 (QOLIE-31-P) Score
Hide Description The QOLIE-31-P is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into seven multi-item subscales - Seizure Worry (5 items), Overall Quality of Life (2 items), Emotional Well-Being (5 items), Energy/Fatigue (4 items), Cognitive Functioning (6 items), Medication Effects (3 items) and Daily Activities/Social Functioning (5 items) - and a Health Status item. The subscale scores, the Total score and the Health Status item score are calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100 and higher scores indicating better function. A positive value in Change from Baseline indicates an improvement from Baseline.
Time Frame From Baseline to 12-week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects in the Intention-to-treat (ITT) population with measurements at Baseline and Last Visit or Early Discontinuation Visit.
Arm/Group Title Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Hide Arm/Group Description:
Matching Placebo tablets administered twice a day
Brivaracetam 20 mg/day, 10 mg administered twice a day
Brivaracetam 50 mg/day, 25 mg administered twice a day
Brivaracetam 100 mg/day, 50 mg administered twice a day
Overall Number of Participants Analyzed 86 92 95 83
Mean (Standard Deviation)
Unit of Measure: units on a scale
3.49  (19.22) 3.53  (17.04) 1.95  (20.74) 1.99  (20.42)
19.Secondary Outcome
Title Change From Baseline to the 12-week Treatment Period in Emotional Well-Being Patient Weighted Quality of Life in Epilepsy Inventory-Form 31 (QOLIE-31-P) Score
Hide Description The QOLIE-31-P is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into seven multi-item subscales - Seizure Worry (5 items), Overall Quality of Life (2 items), Emotional Well-Being (5 items), Energy/Fatigue (4 items), Cognitive Functioning (6 items), Medication Effects (3 items) and Daily Activities/Social Functioning (5 items) - and a Health Status item. The subscale scores, the Total score and the Health Status item score are calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100 and higher scores indicating better function. A positive value in Change from Baseline indicates an improvement from Baseline.
Time Frame From Baseline to 12-week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects in the Intention-to-treat (ITT) population with measurements at Baseline and Last Visit or Early Discontinuation Visit.
Arm/Group Title Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Hide Arm/Group Description:
Matching Placebo tablets administered twice a day
Brivaracetam 20 mg/day, 10 mg administered twice a day
Brivaracetam 50 mg/day, 25 mg administered twice a day
Brivaracetam 100 mg/day, 50 mg administered twice a day
Overall Number of Participants Analyzed 88 93 96 84
Mean (Standard Deviation)
Unit of Measure: units on a scale
3.80  (18.71) 3.75  (15.94) 3.13  (19.35) -2.45  (18.55)
20.Secondary Outcome
Title Change From Baseline to the 12-week Treatment Period in Cognitive Functioning Patient Weighted Quality of Life in Epilepsy Inventory-Form 31 (QOLIE-31-P) Score
Hide Description The QOLIE-31-P is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into seven multi-item subscales - Seizure Worry (5 items), Overall Quality of Life (2 items), Emotional Well-Being (5 items), Energy/Fatigue (4 items), Cognitive Functioning (6 items), Medication Effects (3 items) and Daily Activities/Social Functioning (5 items) - and a Health Status item. The subscale scores, the Total score and the Health Status item score are calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100 and higher scores indicating better function. A positive value in Change from Baseline indicates an improvement from Baseline.
Time Frame From Baseline to 12-week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects in the Intention-to-treat (ITT) population with measurements at Baseline and Last Visit or Early Discontinuation Visit.
Arm/Group Title Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Hide Arm/Group Description:
Matching Placebo tablets administered twice a day
Brivaracetam 20 mg/day, 10 mg administered twice a day
Brivaracetam 50 mg/day, 25 mg administered twice a day
Brivaracetam 100 mg/day, 50 mg administered twice a day
Overall Number of Participants Analyzed 88 93 96 85
Mean (Standard Deviation)
Unit of Measure: units on a scale
1.80  (19.16) 5.36  (20.69) 1.02  (19.95) 0.69  (16.66)
21.Secondary Outcome
Title Change From Baseline to the 12-week Treatment Period in Medication Effects Patient Weighted Quality of Life in Epilepsy Inventory-Form 31 (QOLIE-31-P) Score
Hide Description The QOLIE-31-P is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into seven multi-item subscales - Seizure Worry (5 items), Overall Quality of Life (2 items), Emotional Well-Being (5 items), Energy/Fatigue (4 items), Cognitive Functioning (6 items), Medication Effects (3 items) and Daily Activities/Social Functioning (5 items) - and a Health Status item. The subscale scores, the Total score and the Health Status item score are calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100 and higher scores indicating better function. A positive value in Change from Baseline indicates an improvement from Baseline.
Time Frame From Baseline to 12-week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects in the Intention-to-treat (ITT) population with measurements at Baseline and Last Visit or Early Discontinuation Visit.
Arm/Group Title Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Hide Arm/Group Description:
Matching Placebo tablets administered twice a day
Brivaracetam 20 mg/day, 10 mg administered twice a day
Brivaracetam 50 mg/day, 25 mg administered twice a day
Brivaracetam 100 mg/day, 50 mg administered twice a day
Overall Number of Participants Analyzed 88 92 96 86
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.92  (28.93) 3.64  (29.24) -0.85  (24.36) 3.00  (28.22)
22.Secondary Outcome
Title Change From Baseline to the 12-week Treatment Period in Overall Quality of Life Patient Weighted Quality of Life in Epilepsy Inventory-Form 31 (QOLIE-31-P) Score
Hide Description The QOLIE-31-P is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into seven multi-item subscales - Seizure Worry (5 items), Overall Quality of Life (2 items), Emotional Well-Being (5 items), Energy/Fatigue (4 items), Cognitive Functioning (6 items), Medication Effects (3 items) and Daily Activities/Social Functioning (5 items) - and a Health Status item. The subscale scores, the Total score and the Health Status item score are calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100 and higher scores indicating better function. A positive value in Change from Baseline indicates an improvement from Baseline.
Time Frame From Baseline to 12-week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects in the Intention-to-treat (ITT) population with measurements at Baseline and Last Visit or Early Discontinuation Visit.
Arm/Group Title Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Hide Arm/Group Description:
Matching Placebo tablets administered twice a day
Brivaracetam 20 mg/day, 10 mg administered twice a day
Brivaracetam 50 mg/day, 25 mg administered twice a day
Brivaracetam 100 mg/day, 50 mg administered twice a day
Overall Number of Participants Analyzed 88 93 95 86
Mean (Standard Deviation)
Unit of Measure: units on a scale
5.11  (18.48) 4.52  (16.73) 4.55  (18.93) 2.24  (18.45)
23.Secondary Outcome
Title Change From Baseline to the 12-week Treatment Period in Health Status of Life Patient Weighted Quality of Life in Epilepsy Inventory-Form 31 (QOLIE-31-P) Score
Hide Description The QOLIE-31-P is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into seven multi-item subscales - Seizure Worry (5 items), Overall Quality of Life (2 items), Emotional Well-Being (5 items), Energy/Fatigue (4 items), Cognitive Functioning (6 items), Medication Effects (3 items) and Daily Activities/Social Functioning (5 items) - and a Health Status item. The subscale scores, the Total score and the Health Status item score are calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100 and higher scores indicating better function. A positive value in Change from Baseline indicates an improvement from Baseline.
Time Frame From Baseline to 12-week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects in the Intention-to-treat (ITT) population with measurements at Baseline and Last Visit or Early Discontinuation Visit.
Arm/Group Title Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Hide Arm/Group Description:
Matching Placebo tablets administered twice a day
Brivaracetam 20 mg/day, 10 mg administered twice a day
Brivaracetam 50 mg/day, 25 mg administered twice a day
Brivaracetam 100 mg/day, 50 mg administered twice a day
Overall Number of Participants Analyzed 88 93 95 84
Mean (Standard Deviation)
Unit of Measure: units on a scale
6.6  (16.3) 6.9  (20.1) 9.7  (19.8) 4.9  (18.1)
Time Frame Adverse Events (AEs) were collected up to 23 weeks from Visit 1 (Week -8) to the Safety Visit (Week 15).
Adverse Event Reporting Description Adverse Events (AEs) refer to the Safety Set (SS) population wich contains the same set of subjects as the Intention-To-Treat (ITT) population.
 
Arm/Group Title Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Hide Arm/Group Description Matching Placebo tablets administered twice a day Brivaracetam 20 mg/day, 10 mg administered twice a day Brivaracetam 50 mg/day, 25 mg administered twice a day Brivaracetam 100 mg/day, 50 mg administered twice a day
All-Cause Mortality
Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Hide Serious Adverse Events
Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/100 (6.00%)      2/99 (2.02%)      4/99 (4.04%)      2/100 (2.00%)    
Cardiac disorders         
Angina pectoris * 1  1/100 (1.00%)  1 0/99 (0.00%)  0 0/99 (0.00%)  0 0/100 (0.00%)  0
Gastrointestinal disorders         
Gastritis erosive * 1  0/100 (0.00%)  0 0/99 (0.00%)  0 1/99 (1.01%)  1 0/100 (0.00%)  0
Infections and infestations         
Sepsis * 1  1/100 (1.00%)  1 0/99 (0.00%)  0 0/99 (0.00%)  0 0/100 (0.00%)  0
Injury, poisoning and procedural complications         
Humerus fracture * 1  0/100 (0.00%)  0 0/99 (0.00%)  0 0/99 (0.00%)  0 1/100 (1.00%)  1
Jaw fracture * 1  0/100 (0.00%)  0 1/99 (1.01%)  1 0/99 (0.00%)  0 0/100 (0.00%)  0
Nervous system disorders         
Convulsion * 1  3/100 (3.00%)  4 0/99 (0.00%)  0 1/99 (1.01%)  1 0/100 (0.00%)  0
Grand mal convulsion * 1  0/100 (0.00%)  0 0/99 (0.00%)  0 1/99 (1.01%)  1 0/100 (0.00%)  0
Status epilepticus * 1  0/100 (0.00%)  0 0/99 (0.00%)  0 0/99 (0.00%)  0 1/100 (1.00%)  1
Pregnancy, puerperium and perinatal conditions         
Abortion spontaneous * 1  0/100 (0.00%)  0 1/99 (1.01%)  1 0/99 (0.00%)  0 0/100 (0.00%)  0
Pregnancy * 1  1/100 (1.00%)  1 0/99 (0.00%)  0 0/99 (0.00%)  0 0/100 (0.00%)  0
Psychiatric disorders         
Amnesia * 1  0/100 (0.00%)  0 0/99 (0.00%)  0 1/99 (1.01%)  1 0/100 (0.00%)  0
Psychotic Disorder * 1  0/100 (0.00%)  0 0/99 (0.00%)  0 1/99 (1.01%)  1 0/100 (0.00%)  0
Reproductive system and breast disorders         
Vaginal hemorrhage * 1  0/100 (0.00%)  0 1/99 (1.01%)  1 0/99 (0.00%)  0 0/100 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (9.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Brivaracetam 20 mg/Day Brivaracetam 50 mg/Day Brivaracetam 100 mg/Day
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   22/100 (22.00%)      31/99 (31.31%)      35/99 (35.35%)      37/100 (37.00%)    
Ear and labyrinth disorders         
Vertigo * 1  3/100 (3.00%)  5 1/99 (1.01%)  2 2/99 (2.02%)  2 8/100 (8.00%)  26
Gastrointestinal disorders         
Nausea * 1  4/100 (4.00%)  4 0/99 (0.00%)  0 1/99 (1.01%)  1 6/100 (6.00%)  7
General disorders         
Fatigue * 1  2/100 (2.00%)  2 3/99 (3.03%)  4 4/99 (4.04%)  5 8/100 (8.00%)  9
Infections and infestations         
Nasopharyngitis * 1  1/100 (1.00%)  1 8/99 (8.08%)  8 1/99 (1.01%)  1 2/100 (2.00%)  2
Nervous system disorders         
Convulsion * 1  1/100 (1.00%)  1 5/99 (5.05%)  7 1/99 (1.01%)  1 2/100 (2.00%)  2
Dizziness * 1  5/100 (5.00%)  11 5/99 (5.05%)  8 7/99 (7.07%)  12 5/100 (5.00%)  5
Headache * 1  10/100 (10.00%)  14 14/99 (14.14%)  19 18/99 (18.18%)  31 9/100 (9.00%)  15
Somnolence * 1  6/100 (6.00%)  6 8/99 (8.08%)  10 6/99 (6.06%)  7 8/100 (8.00%)  8
Psychiatric disorders         
Irritability * 1  0/100 (0.00%)  0 0/99 (0.00%)  0 5/99 (5.05%)  5 1/100 (1.00%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (9.0)
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: UCB Clinical Trial Call Center
Organization: UCB
Phone: +1 877 822 9493
Publications of Results:
Ryvlin P, Werhahn KJ, Blaszczyk B, Johnson ME, Lu S. Adjunctive brivaracetam in adults with uncontrolled focal epilepsy: results from a double-blind, randomized, placebo-controlled trial. Epilepsia. 2014 Jan;55(1):47-56. doi: 10.1111/epi.12432. Epub 2013 Oct 28.
Toledo M, Whitesides J, Schiemann J, Johnson ME, Eckhardt K, McDonough B, Borghs S, Kwan P. Safety, tolerability, and seizure control during long-term treatment with adjunctive brivaracetam for partial-onset seizures. Epilepsia. 2016 Jul;57(7):1139-51. doi: 10.1111/epi.13416. Epub 2016 Jun 6.
Ben-Menachem E, Mameniškienė R, Quarato PP, Klein P, Gamage J, Schiemann J, Johnson ME, Whitesides J, McDonough B, Eckhardt K. Efficacy and safety of brivaracetam for partial-onset seizures in 3 pooled clinical studies. Neurology. 2016 Jul 19;87(3):314-23. doi: 10.1212/WNL.0000000000002864. Epub 2016 Jun 22.
Brodie MJ, Whitesides J, Schiemann J, D'Souza J, Johnson ME. Tolerability, safety, and efficacy of adjunctive brivaracetam for focal seizures in older patients: A pooled analysis from three phase III studies. Epilepsy Res. 2016 Nov;127:114-118. doi: 10.1016/j.eplepsyres.2016.08.018. Epub 2016 Aug 18.
Mukuria C, Young T, Keetharuth A, Borghs S, Brazier J. Sensitivity and responsiveness of the EQ-5D-3L in patients with uncontrolled focal seizures: an analysis of Phase III trials of adjunctive brivaracetam. Qual Life Res. 2017 Mar;26(3):749-759. doi: 10.1007/s11136-016-1483-3. Epub 2016 Dec 21.
Moseley BD, Sperling MR, Asadi-Pooya AA, Diaz A, Elmouft S, Schiemann J, Whitesides J. Efficacy, safety, and tolerability of adjunctive brivaracetam for secondarily generalized tonic-clonic seizures: Pooled results from three Phase III studies. Epilepsy Res. 2016 Nov;127:179-185. doi: 10.1016/j.eplepsyres.2016.09.003. Epub 2016 Sep 3.
Brandt C, Borghs S, Elmoufti S, Mueller K, Townsend R, de la Loge C. Health-related quality of life in double-blind Phase III studies of brivaracetam as adjunctive therapy of focal seizures: A pooled, post-hoc analysis. Epilepsy Behav. 2017 Apr;69:80-85. doi: 10.1016/j.yebeh.2016.11.031. Epub 2017 Feb 23.
Klein P, Johnson ME, Schiemann J, Whitesides J. Time to onset of sustained ≥50% responder status in patients with focal (partial-onset) seizures in three phase III studies of adjunctive brivaracetam treatment. Epilepsia. 2017 Feb;58(2):e21-e25. doi: 10.1111/epi.13631. Epub 2016 Dec 18.
Asadi-Pooya AA, Sperling MR, Chung S, Klein P, Diaz A, Elmoufti S, Schiemann J, Whitesides J. Efficacy and tolerability of adjunctive brivaracetam in patients with prior antiepileptic drug exposure: A post-hoc study. Epilepsy Res. 2017 Mar;131:70-75. doi: 10.1016/j.eplepsyres.2017.02.007. Epub 2017 Feb 27. Erratum in: Epilepsy Res. 2017 Nov;137:165-166.
Benbadis S, Klein P, Schiemann J, Diaz A, Elmoufti S, Whitesides J. Efficacy, safety, and tolerability of brivaracetam with concomitant lamotrigine or concomitant topiramate in pooled Phase III randomized, double-blind trials: A post-hoc analysis. Epilepsy Behav. 2018 Mar;80:129-134. doi: 10.1016/j.yebeh.2017.12.024. Epub 2018 Feb 3.
Brodie MJ, Fakhoury T, McDonough B, Colson AO, Stockis A, Elmoufti S, Whitesides J. Brivaracetam-induced elevation of carbamazepine epoxide levels: A post-hoc analysis from the clinical development program. Epilepsy Res. 2018 Sep;145:55-62. doi: 10.1016/j.eplepsyres.2018.06.002. Epub 2018 Jun 4.
Klein P, Laloyaux C, Elmoufti S, Gasalla T, Martin MS. Time course of 75%-100% efficacy response of adjunctive brivaracetam. Acta Neurol Scand. 2020 Aug;142(2):175-180. doi: 10.1111/ane.13287. Epub 2020 Jun 9.
Layout table for additonal information
Responsible Party: UCB Pharma ( UCB Pharma SA )
ClinicalTrials.gov Identifier: NCT00490035    
Other Study ID Numbers: N01252
2006-006344-59 ( EudraCT Number )
First Submitted: June 21, 2007
First Posted: June 22, 2007
Results First Submitted: March 14, 2016
Results First Posted: April 13, 2016
Last Update Posted: August 31, 2020