Brivaracetam Efficacy and Safety Study in Subjects With Partial Onset Seizures (BRITE™)

• Percent reduction over placebo for partial onset seizure (Type I) frequency over the Treatment Period standardized to a 28-day duration [ Time Frame: 12 week Treatment Period ] [ Designated as safety issue: No ]
  Primary endpoint: United States of America (FDA)
• 50% responder rate for partial onset seizure (Type I) frequency over the Treatment Period standardized to a 28-day duration [ Time Frame: Baseline to 12 week Treatment Period ] [ Designated as safety issue: No ]
  Primary Endpoint: European Regulatory Authorities

• Percent reduction in partial onset seizure (Type I) frequency from the Baseline to the Treatment Period [ Time Frame: Baseline to 12 week Treatment Period ] [ Designated as safety issue: No ]
• Categorized percent reduction form Baseline in seizure frequency for partial onset seizure (Type I) over the Treatment Period [ Time Frame: Baseline to 12 week Treatment Period ] [ Designated as safety issue: No ]
• Seizure freedom rate (all seizure types) during the 12-week Treatment Period [ Time Frame: 12 week Treatment Period ] [ Designated as safety issue: No ]
• All seizure frequency (Type I + II + III) during the 12-week Treatment Period [ Time Frame: 12 week Treatment Period ] [ Designated as safety issue: No ]
• Time to the first Type I seizure during the Treatment Period [ Time Frame: 12 week Treatment Period ] [ Designated as safety issue: No ]
• Time to the fifth Type I seizure during the Treatment Period [ Time Frame: 12 week Treatment Period ] [ Designated as safety issue: No ]
• Time to the tenth Type I seizure during the Treatment Period [ Time Frame: 12 week Treatment Period ] [ Designated as safety issue: No ]

• Percent reduction in partial onset seizure (Type I) frequency from the Baseline to the Treatment Period [ Time Frame: Average over 12 week Treatment Period standardized to a 28-day duration ] [ Designated as safety issue: No ]
• Categorized percent reduction form Baseline in seizure frequency for partial onset seizure (Type I) over the Treatment Period [ Time Frame: Average over 12 week Treatment Period standardized to a 28-day duration ] [ Designated as safety issue: No ]
• Seizure freedom rate (all seizure types) during the 12-week Treatment Period [ Time Frame: Average over 12 week Treatment Period standardized to a 28-day duration ] [ Designated as safety issue: No ]
• All seizure frequency (Type I + II + III) during the 12-week Treatment Period [ Time Frame: Average over 12 week Treatment Period standardized to a 28-day duration ] [ Designated as safety issue: No ]
• Time to the first Type I seizure during the Treatment Period [ Time Frame: Average over 12 week Treatment Period standardized to a 28-day duration ] [ Designated as safety issue: No ]
• Time to the fifth Type I seizure during the Treatment Period [ Time Frame: Average over 12 week Treatment Period standardized to a 28-day duration ] [ Designated as safety issue: No ]
• Time to the tenth Type I seizure during the Treatment Period [ Time Frame: Average over 12 week Treatment Period standardized to a 28-day duration ] [ Designated as safety issue: No ]

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.

• Drug: Placebo
  Daily oral dose of two equal intakes of placebo in a double-blinded way for the 12-week treatment period
• Drug: Brivaracetam
  Daily oral dose of two equal intakes of Brivaracetam 100 mg/day in a double-blinded way for the 12-week treatment period
• Drug: Brivaracetam
  Daily oral dose of two equal intakes of Brivaracetam 200 mg/day in a double-blinded way for the 12-week treatment period.

• Placebo Comparator: Placebo
  Matching placebo tablets administered twice daily
  Intervention: Drug: Placebo
• Experimental: Brivaracetam 100 mg/day
  Brivaracetam 50 mg/day administered twice daily.
  Intervention: Drug: Brivaracetam
• Experimental: Brivaracetam 200 mg/day
  Brivaracetam 100 mg/day administered twice daily
  Intervention: Drug: Brivaracetam

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