Brivaracetam Efficacy and Safety Study in Subjects With Partial Onset Seizures

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of brivaracetam at doses of 100 and 200mg/day compared to placebo as adjunctive treatment in adult focal epilepsy subjects with partial onset seizures not fully controlled despite current treatment with 1 or 2 concomitant antiepileptic drugs.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel-group Study to Evaluate the Efficacy and Safety of Brivaracetam in Subjects (≥16 to 80 Years Old) With Partial Onset Seizures

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: Placebo
* Drug: Brivaracetam
* Drug: Brivaracetam
* Drug: Antiepileptic drugs with market authorization available per country


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Well-characterized focal epilepsy/epileptic syndrome according to the 1989 International League Against Epilepsy (ILAE) classification Presence of an EEG reading compatible with the clinical diagnosis of focal epilepsy within the last 5 years Presence of a brain MRI/computed tomography (CT) scan performed within the last 2 years Subjects having at least 8 Type I seizures [POS; focal seizures (according to the 1981 ILAE classification)] during the 8-week Baseline Period with at least 2 Type I seizures during each 4-week interval of the Baseline Period Subjects having at least 2 partial onset seizures whether or not secondarily generalized per month during the 3 months preceding V1 Subjects being uncontrolled while treated by 1 or 2 permitted concomitant AED(s). Vagal Nerve Stimulation (VNS) is allowed and will be counted as a concomitant AED Permitted concomitant AED(s) and VNS being stable and at optimal dosage for the subject from at least 1 month (3 months for phenobarbital, phenytoin, and primidone) before V1 and expected to be kept stable during the Baseline and Treatment Period. Benzodiazepine taken more than once a week (for any indication) will be considered as a concomitant AED Exclusion Criteria: Subject previously randomized within this study or any other prior study with BRV as a dosing arm Seizure type IA (1981 ILAE classification) nonmotor as only seizure type. Subject is currently treated with LEV or has taken LEV within 90 days prior to V1 Subject has any medical or psychiatric condition, obvious cognitive impairment or mental retardation that, in the opinion of the Investigator, could jeopardize or would compromise the subject's ability to participate in this study Subjects whose seizures could not be reliably counted on a regular basis due to their fast and repetitive occurrence (clusters or flurries) Subject has history or presence of status epilepticus during the year preceding V1 or during Baseline Subject has history or presence of known psychogenic nonepileptic seizures Subject on felbamate with less than 18 months exposure before V1 Subject currently on vigabatrin. Subject with history of vigabatrin use but either no visual fields examination report available including standard static (Humphrey or Octopus) or kinetic perimetry (Goldman) or results of these examinations are abnormal Subject taking any drug with possible central nervous system (CNS) effects except if stable from at least 1 month before V1 and expected to be kept stable during the Treatment Period Subject has history of cerebrovascular accident, including transient ischemic attack, in the last 6 months Subject is suffering from severe cardiovascular disease or peripheral vascular disease Subject has a lifetime history of suicide attempt or has suicidal ideation in the past 6 months Subject has ongoing psychiatric disease other than mild controlled disorder

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 80 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 daily | Drug: Placebo<br>* Daily oral dose of two equal intakes of placebo in a double-blinded way for the 12-week treatment period<br>Drug: Antiepileptic drugs with market authorization available per country<br> <br> |
| Experimental: Brivaracetam 100 mg/ day<br>Brivaracetam 50 mg/ day administered twice daily. | Drug: Brivaracetam<br>* Daily oral dose of two equal intakes of Brivaracetam 100 mg/ day in a double-blinded way for the 12-week treatment period<br>Drug: Antiepileptic drugs with market authorization available per country<br> <br> |
| Experimental: Brivaracetam 200 mg/ day<br>Brivaracetam 100 mg/ day administered twice daily | Drug: Brivaracetam<br>* Daily oral dose of two equal intakes of Brivaracetam 200 mg/ day in a double-blinded way for the 12-week treatment period.<br>Drug: Antiepileptic drugs with market authorization available per country<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Reduction Over Placebo for Partial Onset Seizure (Type I) Frequency Over the Treatment Period Standardized to a 28-day Duration | Primary endpoint: United States of America (FDA) | 12 week Treatment Period | 
| 50% Responder Rate for Partial Onset Seizure (Type I) Frequency Over the Treatment Period Standardized to a 28-day Duration | Primary Endpoint: European Regulatory Authorities A responder is a participant who experienced a 50% or greater reduction in partial onset seizure (Type I) frequency over the Treatment Period standardized to a 28-day duration. | Baseline to 12 week Treatment Period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Partial Onset Seizure (Type I) Frequency From the Baseline to the Treatment Period |  | Baseline to 12 week Treatment Period | 
| Categorized Percent Reduction Form Baseline in Seizure Frequency for Partial Onset Seizure (Type I) Over the Treatment Period |  | Baseline to 12 week Treatment Period | 
| Seizure Freedom Rate (All Seizure Types) During the 12-week Treatment Period |  | 12 week Treatment Period | 
| All Seizure Frequency (Type I + II + III) During the 12-week Treatment Period |  | 12 week Treatment Period | 
| Time to the First Type I Seizure During the Treatment Period |  | 12 week Treatment Period | 
| Time to the Fifth Type I Seizure During the Treatment Period |  | 12 week Treatment Period | 
| Time to the Tenth Type I Seizure During the Treatment Period |  | 12 week Treatment Period | 

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