Double-blind, Randomized Study Evaluating the Efficacy and Safety of Brivaracetam in Adults With Partial Onset Seizures
- Registration Number
- NCT00490035
- Lead Sponsor
- UCB Pharma SA
- Brief Summary
This study will evaluate the efficacy and safety of Brivaracetam to support the submission file in the indication of adjunctive treatment in adolescents and adults with partial onset seizures.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 399
- Subjects were from 16 to 70 years, both inclusive. Subjects under 18 years of age were only included where legally permitted and ethically accepted
- Subjects with well-characterized focal epilepsy or epileptic syndrome according to the International League Against Epilepsy (ILAE) classification
- Subjects had a history of partial onset seizures (POS) whether or not secondarily generalized (Type I seizures according to the ILAE classification)
- Subjects had at least 2 POS whether or not secondarily generalized per month during the 3 months preceding Visit 1
- Subjects had at least 8 POS whether or not secondarily generalized during the 8-Week Baseline Period
- Subjects were uncontrolled while treated by 1 to 2 permitted concomitant antiepileptic drugs (AEDs). Vagal nerve stimulation was allowed and was not counted as a concomitant AED
- History or presence of seizures occurring only in clusters (too frequently or indistinctly separated to be reliably counted) before Visit 3
- History or presence of status epilepticus during the year preceding Visit 1 or during Baseline
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Matching Placebo tablets administered twice a day Brivaracetam 50 mg/day Brivaracetam Brivaracetam 50 mg/day, 25 mg administered twice a day Brivaracetam 100 mg/day Brivaracetam Brivaracetam 100 mg/day, 50 mg administered twice a day Brivaracetam 20 mg/day Brivaracetam Brivaracetam 20 mg/day, 10 mg administered twice a day
- Primary Outcome Measures
Name Time Method Partial Onset Seizure (Type I) Frequency Per Week Over the 12-week Treatment Period From Baseline to 12-week Treatment Period 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.
- Secondary Outcome Measures
Name Time Method Categorized Percentage Change From Baseline in Seizure Frequency for Partial Onset Seizure (Type I) Over the 12-week Treatment Period From Baseline to 12-week Treatment Period The categories are:
* \<= 25 %
* - 25 % to \< 25 %
* 25 % to \< 50 %
* 50 % to \< 75 %
* 75 % to \< 100 %
* 100 %Time to Fifth Type I Seizure During the 12-week Treatment Period From Baseline to 12-week Treatment Period The time to Fifth Type I Seizure during the 12-week Treatment Period was measured in days.
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 From Baseline to 12-week Treatment Period 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.
Responder Rate for Partial Onset Seizures (Type I) Frequency Per Week Over the 12-week Treatment Period From Baseline to 12-week Treatment Period 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.Seizure Freedom Rate (All Seizure Types) Over the 12-week Treatment Period From Baseline to 12-week Treatment Period 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.
Patient's Global Evaluation Scale (P-GES) Evaluated at Last Visit or Early Discontinuation Visit Last Visit or Early Discontinuation Visit in the 12-week Treatment Period 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?"
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 From Baseline to 12-week Treatment Period 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 to First Type I Seizure During the 12-week Treatment Period From Baseline to 12-week Treatment Period The time to first Type I Seizure during the 12-week Treatment Period was measured in days.
Time to Tenth Type I Seizure During the 12-week Treatment Period From Baseline to 12-week Treatment Period The time to tenth Type I Seizure during the 12-week Treatment Period was measured in days.
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 From Baseline to 12-week Treatment Period 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.
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 From Baseline to 12-week Treatment Period 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.
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 From Baseline to 12-week Treatment Period 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.
All Seizure Frequency (Type I+II+III) Per Week Over the 12-week Treatment Period From Baseline to 12-week Treatment Period There are three types of Epilepsy: Partial Epilepsies (Type I), Generalized Epilepsies (Type II) and uncertain classification of Epilepsies (Type III).
Percent Change From Baseline to the 12-week Treatment Period in Partial Onset Seizure (Type I) Frequency Per Week From Baseline to 12-week Treatment Period 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.
Reduction of Type IC/Type I Seizure Frequency Ratio From Baseline to the 12- Week Treatment Period. From Baseline to 12-week Treatment Period 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.
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 From Baseline to 12-week Treatment Period 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.
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 From Baseline to 12-week Treatment Period 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.
Change From Baseline to the 12-week Treatment Period in Hospital Anxiety Score From Baseline to 12-week Treatment Period 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.
Investigator's Global Evaluation Scale (I-GES) Evaluated at Last Visit or Early Discontinuation Visit Last Visit or Early Discontinuation Visit in the 12-week Treatment Period 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."
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 From Baseline to 12-week Treatment Period 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.
Change From Baseline to the 12-week Treatment Period in Hospital Depression Score From Baseline to 12-week Treatment Period 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.
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 From Baseline to 12-week Treatment Period 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.
Trial Locations
- Locations (76)
52
🇫🇷Montpellier Cedex, France
71
🇩🇪Ulm, Germany
94
ðŸ‡ðŸ‡ºBudapest, Hungary
259
🇮🇳Mumbai, India
145
🇵🇱Warsaw, Poland
140
🇵🇱Warszawa, Poland
44
🇫🇮Kuopio, Finland
92
ðŸ‡ðŸ‡ºPecs, Hungary
257
🇮🇳Bangalore, India
253
🇮🇳Hyderabad, India
10
🇧🇪Saint-Vith, Belgium
149
🇵🇱Warszawa, Poland
224
🇬🇧Middlesborough, United Kingdom
13
🇧🇪Gent, Belgium
19
🇧🇪La Louviere, Belgium
12
🇧🇪Liege, Belgium
42
🇫🇮Seinajoki, Finland
41
🇫🇮Oulu, Finland
43
🇫🇮Tampere, Finland
56
🇫🇷Bethune, France
60
🇫🇷Angers Cedex 9, France
62
🇫🇷Bron, France
57
🇫🇷Dijon, France
53
🇫🇷Lille, France
64
🇫🇷Nancy, France
54
🇫🇷Paris, France
51
🇫🇷Rennes, France
61
🇫🇷Roanne, France
55
🇫🇷Strasbourg, France
76
🇩🇪Bad Berka, Germany
79
🇩🇪Bernau, Germany
73
🇩🇪Berlin, Germany
78
🇩🇪Bielefeld, Germany
74
🇩🇪Freiburg, Germany
70
🇩🇪Munchen, Germany
75
🇩🇪Kehl-Kork, Germany
77
🇩🇪Mainz, Germany
72
🇩🇪Radeberg, Germany
90
ðŸ‡ðŸ‡ºDebrecen, Hungary
256
🇮🇳Bangalore, India
255
🇮🇳Kolkata, India
250
🇮🇳Lucknow, India
258
🇮🇳Jaipur, India
270
🇮🇳Pune, India
251
🇮🇳Pune Maharashtra, India
104
🇮🇹Bologna, Italy
105
🇮🇹Foggia, Italy
101
🇮🇹Perugia, Italy
107
🇮🇹Roma, Italy
103
🇮🇹Roma, Italy
124
🇳🇱Breda, Netherlands
125
🇳🇱Den Haag, Netherlands
142
🇵🇱Bialystok, Poland
143
🇵🇱Gdansk, Poland
122
🇳🇱Zwolle, Netherlands
141
🇵🇱Kielce, Poland
153
🇵🇱Grodzisk Mazowiecki, Poland
147
🇵🇱Katowice, Poland
151
🇵🇱Katowice, Poland
150
🇵🇱Krakow, Poland
146
🇵🇱Szczecin, Poland
144
🇵🇱Lublin, Poland
148
🇵🇱Lodz, Poland
152
🇵🇱Poznan, Poland
181
🇪🇸Barcelona, Spain
187
🇪🇸Alcorcon, Spain
182
🇪🇸Madrid, Spain
184
🇪🇸San Sebastian, Spain
203
🇨ðŸ‡St Gallen, Switzerland
183
🇪🇸Vigo, Spain
201
🇨ðŸ‡Biel, Switzerland
205
🇨ðŸ‡Geneve, Switzerland
185
🇪🇸Zaragoza, Spain
202
🇨ðŸ‡Tschugg, Switzerland
204
🇨ðŸ‡Zürich, Switzerland
223
🇬🇧Liverpool, United Kingdom