A Dose-ranging Study With Brivaracetam in Patients From 16 to 65 Years With Refractory Partial Onset Seizures.

Study Overview
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Brief Summary
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This trial will evaluate the efficacy and safety of brivaracetam (at doses of 5, 20 and 50 mg/day in twice a day administration) as add-on therapy in subjects with focal epilepsy.

Official Title
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A Multicenter, Double-blind, Randomized, Placebo-controlled, 4 Parallel Groups, Dose-ranging Trial Evaluating the Efficacy and Safety of Brivaracetam Used as Adjunctive Treatment at Doses of 5, 20 and 50 mg/Day in b.i.d. Administration (Oral Tablets of 2.5 or 10 mg) for a Maximum of 7 Weeks in Subjects From 16 to 65 Years With Refractory Epilepsy Suffering From Partial Onset Seizures Whether or Not Secondarily Generalized

Conditions
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Epilepsy

Intervention / Treatment
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* Other: Placebo
* Drug: Brivaracetam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male/female from 16 to 65 years Well-characterized focal epilepsy or epileptic syndrome according to the International League Against Epilepsy (ILAE) classification History of partial onset seizures Subjects having at least 4 partial onset seizures during the 4-week Baseline Period and at least 2 partial onset seizures during the 3 months prior to Visit 1 Subjects taking 1 or 2 concomitant Antiepileptic drugs (AED(s)) that have been at a stable dose. Exclusion Criteria: Seizure type IA non-motor as only seizure type Seizures occurring only in clusters Status epilepticus during the last 2 years before Visit 1 History of cerebrovascular accident (CVA) Presence of any sign suggesting rapidly progressing brain disorder or brain tumor

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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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 7-week Treatment Period<br>|
| Experimental: Brivaracetam 5 mg/day<br>Brivaracetam 5 mg/day, 2.5 mg administered twice a day | Drug: Brivaracetam<br>* Daily oral dose of two equal intakes, morning and evening, of Brivaracetam over the 7-week Treatment Period<br>* Other names: Briviact;|
| 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 over the 7-week Treatment Period<br>* Other names: Briviact;|
| 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 over the 7-week Treatment Period<br>* Other names: Briviact;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Partial Onset Seizure Frequency Per Week During the 7-week Treatment Period | Calculated as 7-day partial onset seizure frequency. | During the 7-week Treatment Period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline in Partial Onset Seizure Frequency Per Week (Type I) Over the 7-week Treatment Period | Calculated as 7-day seizure frequency during the 7-week Treatment Period - 7-day seizure frequency during the Baseline Period, divided by the 7-day seizure frequency during the Baseline Period with this quantity multiplied by 100. A negative value in percent change from Baseline indicates a decrease in partial seizure frequency from Baseline. | Baseline, during the 7-week Treatment Period | 
| Seizure Frequency Per Week for All Seizures (Types I +II +III) Over the Treatment Period | Types I+II+III seizure frequency (Type I: Partial (focal, local), Type II: Generalized (convulsive or nonconvulsive), Type III: Unclassified) per week will be derived from the seizure count information recorded on the daily record card (e.g. date, number, type of epileptic seizures) and is defined as the number of seizures standardized to a 7-day period. | During the 7-week Treatment Period | 
| Absolute Change From Baseline in Seizure Frequency Per Week for Partial Onset Seizures (Type I) Over the Treatment Period | Calculated as 7-day Partial Onset Seizures (Type I) frequency during the 7-week Treatment Period 7-day seizure frequency during the Baseline Period. A negative value from Baseline indicates a decrease in partial seizure frequency from Baseline. | During the 7-week Treatment Period | 
| Absolute Change From Baseline in Seizure Frequency Per Week for All Seizures (Types I + II + III) Over the Treatment Period | Calculated as 7-day seizure frequency during the 7-week Treatment Period 7-day seizure (Types I + II + III) frequency during the Baseline Period. A negative value from Baseline indicates a decrease in partial seizure frequency from Baseline. | During the 7-week Treatment Period | 
| Percentage Change From Baseline in Seizure Frequency Per Week for All Seizures (Types I + II + III) Over the Treatment Period | Calculated as 7-day seizure frequency during the 7-week Treatment Period - 7-day seizure frequency during the Baseline Period, divided by the 7-day seizure frequency during the Baseline Period with this quantity multiplied by 100. A negative value in percent change from Baseline indicates a decrease in partial seizure frequency from Baseline. | During the 7-week Treatment Period | 
| Responder Rate in Partial Onset Seizures (Type I) Over the Treatment Period | A responder was defined as a subject with a >= 50 % reduction in seizure frequency per week from the Baseline Period to the end of the Treatment Period. | During the 7-week Treatment Period | 
| Percentage of Subjects With Categorized Response to the Treatment in Partial Onset Seizures (Type I) Over the Treatment Period | Categories of percentage reductions in seizures from baseline were as following: < -25 %; -25 % to <25 %; 25 % to <75 %; 75 % to <100 %; 100 %. | During the 7-week Treatment Period | 
| Percentage of Subjects Who Are Seizure Free During the 7-week Treatment Period | A subject was considered seizure free, if no seizure was reported during the 7-week Treatment Period. | During the 7-week Treatment Period | 
| Number of Seizure-free Days Per 4 Weeks | A day was considered seizure-free, if no seizure was reported during 24 hours. | Baseline, during the 7-week Treatment Period | 
| Time to Nth (n= 1, 5, 10) Seizure During the 7-week Treatment Period | Number of days to first, fifth, and tenth seizure after baseline. | During the 7-week Treatment Period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epilepsy: partial onset seizures, brivaracetam