Efficacy and Safety Study of BIA 2-093 in Combination With Other Anti-Epileptic Drugs to Treat Partial Epilepsy

• proportion of responders [ Time Frame: 12-week maintenance ] [ Designated as safety issue: No ]
  patients with a ≥ 50% reduction in seizure frequency during the 12-week maintenance period compared with the 8-week baseline period
• seizure frequency per week for each week of the baseline, titration, and maintenance periods [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• distribution of seizure reduction (< 50%, 50-75%, or > 75% seizure reduction) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• proportion of seizure-free patients (100% seizure reduction) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• proportion of patients with a ≥ 25% exacerbation in seizure frequency compared to baseline [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• seizure frequency by seizure type [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• adverse events [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  Number of AES/patient

• proportion of responders (i.e., patients with a ≥ 50% reduction in seizure frequency during the 12-week maintenance period compared with the 8-week baseline period) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• seizure frequency per week for each week of the baseline, titration, and maintenance periods [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• distribution of seizure reduction (< 50%, 50-75%, or > 75% seizure reduction) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• proportion of seizure-free patients (100% seizure reduction) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• proportion of patients with a ≥ 25% exacerbation in seizure frequency compared to baseline [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• seizure frequency by seizure type [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• incidence of adverse events [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

The primary objective of the study is to evaluate the efficacy of eslicarbazepine acetate once-daily at doses of 400 mg, 800 mg and 1200 mg compared with placebo as adjunctive therapy in patients with refractory partial epilepsy over a 12-week maintenance period. Patients who complete Part I may enter a 1-year open-label extension.

Part I was a 22-week parallel-group, randomized, placebo-controlled period (8 weeks baseline, 2 weeks double-blind titration, and 12 weeks maintenance). After completing the baseline period, patients were randomized in a 1:1:1:1 ratio to 1 of the 3 ESL dose levels or to placebo.

Part II was a 1-year open-label extension for patients who had completed Part I. The starting dose was 800 mg once daily and could be titrated up or down at 400-mg intervals between 400 and 1200 mg.

• Drug: eslicarbazepine acetate
  oral tablets
  Other Name: Zebinix
• Drug: placebo
  once daily placebo comparator

• Experimental: ESL 400 mg once daily
  Intervention: Drug: eslicarbazepine acetate
• Experimental: ESL 800 mg once daily
  Intervention: Drug: eslicarbazepine acetate
• Experimental: ESL 1200 mg once daily
  Intervention: Drug: eslicarbazepine acetate
• Placebo Comparator: placebo
  Intervention: Drug: placebo

Inclusion Criteria:

• written informed consent signed by patient
• aged 18 years or more
• documented diagnosis of simple or complex partial seizures with or without secondary generalisation since at least 12 months prior to screening
• at least 4 partial seizures in each 4 week period during the last 8 weeks prior to screening, currently treated with 1 or 2 AEDs (any except oxcarbazepine and felbamate), in a stable dose regimen during at least 2 months prior to screening (patients using vigabatrin should have been on this medication for at least 1 year with no deficit in visual field identified)
• excepting epilepsy, patient is judged to be in general good health based on medical history, physical examination and laboratory tests
• post-menopausal or otherwise incapable of becoming pregnant by reason of surgery or tubal ligation; in case of woman of childbearing potential, patient must present a serum beta-hCG test consistent with a non-gravid state and agree to remain abstinent or use reliable contraception (oral contraception should be combined with a barrier method

Exclusion Criteria:

• only simple partial seizures with no motor symptomatology (classified as A2-4 according to the International Classification of Epileptic Seizures) that are not video-EEG documented
• primarily generalised epilepsy
• known rapid progressive neurological disorder; history of status epilepticus or cluster seizures (i.e., 3 or more seizures within 30 minutes) within the 3 months prior to screening
• seizures of psychogenic origin within the last 2 years
• history of schizophrenia or suicide attempt
• currently on or with exposure to felbamate or oxcarbazepine more within one month of screening
• using benzodiazepines on more than on an occasional basis (except when used chronically as AED)
• previous use of ESL or participation in a clinical study with ESL
• known hypersensitivity to carbamazepine, oxcarbazepine or chemically related substances
• history of abuse of alcohol, drugs or medications within the last 2 years
• uncontrolled cardiac, renal, hepatic, endocrine, gastrointestinal, metabolic, haematological or oncology disorder
• second or third-degree atrioventricular blockade not corrected with a pacemaker
• relevant clinical laboratory abnormalities