Double-blind, Randomized Study Evaluating the Efficacy and Safety of Brivaracetam in Adults With Partial Onset Seizures

Study Overview
=================
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.

Official Title
-----------------
A Multi-center, Double-blind, Parallel-group, Placebo Controlled, Randomized Study: Evaluation of the Efficacy and Safety of Brivaracetam in Subjects (>= 16 to 70 Years Old) With Partial Onset Seizures.

Conditions
-----------------
Epilepsy

Intervention / Treatment
-----------------
* Other: Placebo
* Drug: Brivaracetam
* Drug: Brivaracetam
* Drug: Brivaracetam


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Matching Placebo tablets administered twice a day | Other: Placebo<br>* Daily oral dose of two equal intakes, morning and evening, of Placebo in a double-blinded way for the 12-week Treatment Period<br>|
| Experimental: Brivaracetam 20 mg/day<br>Brivaracetam 20 mg/day, 10 mg administered twice a day | Drug: Brivaracetam<br>* Daily oral dose of two equal intakes, morning and evening, of Brivaracetam 20 mg /day in a double-blinded way for the 12-week Treatment Period<br>|
| Experimental: Brivaracetam 50 mg/day<br>Brivaracetam 50 mg/day, 25 mg administered twice a day | Drug: Brivaracetam<br>* Daily oral dose of two equal intakes, morning and evening, of Brivaracetam 50 mg /day in a double-blinded way for the 12-week Treatment Period.<br>|
| Experimental: Brivaracetam 100 mg/day<br>Brivaracetam 100 mg/day, 50 mg administered twice a day | Drug: Brivaracetam<br>* Daily oral dose of two equal intakes, morning and evening, of Brivaracetam 100 mg /day in a double-blinded way for the 12-week Treatment Period.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Partial Onset Seizure (Type I) Frequency Per Week Over the 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. | From Baseline to 12-week Treatment Period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder Rate for Partial Onset Seizures (Type I) Frequency Per Week Over the 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. | From Baseline to 12-week Treatment Period | 
| All Seizure Frequency (Type I+II+III) Per Week Over the 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). | From Baseline to 12-week Treatment Period | 
| Percent Change From Baseline to the 12-week Treatment Period in Partial Onset Seizure (Type I) Frequency Per Week | 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. | From Baseline to 12-week Treatment Period | 
| Categorized Percentage Change From Baseline in Seizure Frequency for Partial Onset Seizure (Type I) Over the 12-week Treatment Period | The categories are: <= 25 % - 25 % to < 25 % 25 % to < 50 % 50 % to < 75 % 75 % to < 100 % 100 % | From Baseline to 12-week Treatment Period | 
| Seizure Freedom Rate (All Seizure Types) Over the 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. | From Baseline to 12-week Treatment Period | 
| Time to First Type I Seizure During the 12-week Treatment Period | The time to first Type I Seizure during the 12-week Treatment Period was measured in days. | From Baseline to 12-week Treatment Period | 
| Time to Fifth Type I Seizure During the 12-week Treatment Period | The time to Fifth Type I Seizure during the 12-week Treatment Period was measured in days. | From Baseline to 12-week Treatment Period | 
| Time to Tenth Type I Seizure During the 12-week Treatment Period | The time to tenth Type I Seizure during the 12-week Treatment Period was measured in days. | From Baseline to 12-week Treatment Period | 
| Reduction of Type IC/Type I Seizure Frequency Ratio From Baseline to the 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. | From Baseline to 12-week 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 | 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. | From Baseline to 12-week Treatment Period | 
| 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 | 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. | From Baseline to 12-week Treatment Period | 
| 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 | 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. | From Baseline to 12-week Treatment Period | 
| Change From Baseline to the 12-week Treatment Period in Hospital Anxiety Score | 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. | From Baseline to 12-week Treatment Period | 
| Change From Baseline to the 12-week Treatment Period in Hospital Depression Score | 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. | From Baseline to 12-week Treatment Period | 
| Patient's Global Evaluation Scale (P-GES) Evaluated at Last Visit or Early Discontinuation Visit | 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? | Last Visit or Early Discontinuation Visit in the 12-week Treatment Period | 
| Investigator's Global Evaluation Scale (I-GES) Evaluated at Last Visit or Early Discontinuation Visit | 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. | Last Visit or Early Discontinuation Visit in the 12-week Treatment Period | 
| 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 | 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. | From Baseline to 12-week Treatment Period | 
| 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 | 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. | From Baseline to 12-week Treatment Period | 
| 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 | 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. | From Baseline to 12-week Treatment Period | 
| 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 | 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. | From Baseline to 12-week Treatment Period | 
| 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 | 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. | From Baseline to 12-week 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 | 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. | From Baseline to 12-week Treatment Period | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Epilepsy, Brivaracetam, Partial Onset Seizures