Efficacy and Safety of Eslicarbazepine Acetate as Adjunctive Therapy for Refractory Partial Epilepsy

Phase 3

Completed

Interventions: Drug: placebo (Part I)
Drug: ESL - Open-label Extension (Part II)
Drug: eslicarbazepine acetate

Brief Summary: The primary objective was to evaluate the efficacy of eslicarbazepine acetate (ESL) administered once daily at 1200 mg or 800 mg, compared with placebo as adjunctive therapy in patients with refractory partial epilepsy over a 12-week maintenance period.

Detailed Description: This was a phase III, 2-part multicenter study. Part I was an 26-week parallel-group, randomized, placebo-controlled design consisting of an 8 week baseline period, a 2 week double-blinded titration period, 12 week maintenance period, and a 4 week tapering-off period. After completing the baseline period, patients were randomized in a 1:1:1 ratio to 1 of the 2 ESL daily dose levels (1200 or 800 mg) or placebo.

Part II was a 1-year open-label extension for patients who had completed Part I. Starting at 800 mg/day, the dosage could be titrated at 400 mg intervals down to a minimum of 400 mg/day or up to a maximum of 1200 mg/day. Patients who completed Part II could participate in a study extension and continue treatment with ESL until marketing authorization is obtained or clinical development is discontinued, with visits scheduled at the discretion of the investigator but at least every 6 months.

Results from Part I \& II were presented in two separate reports.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
placebo (Part I)	placebo (Part I)	placebo
ESL - Open-label Extension (Part II)	ESL - Open-label Extension (Part II)	All patients were treated with only ESL during Part II.
ESL 1200 mg daily (Part I)	eslicarbazepine acetate	ESL 1200mg daily
ESL 800 mg daily (Part I)	eslicarbazepine acetate	ESL 800mg daily

Primary Outcome Measures

Name	Time	Method
PART II: Nº of Treatment-Emergent Adverse Events (TEAE)	1-year	The primary objective for Part II of the study was to evaluate the safety and tolerability of eslicarbazepine acetate (ESL, BIA 2-093) at doses titrated to an efficacy or safety endpoint over a 1-year open-label period. Safety assessments were based primarily on AEs (Number of participants with at least one treatment-emergent adverse events are reported); assessment of AEs was based on treatment relatedness, action taken on study drug, outcome, and causality.
Seizure Frequency	12 weeks	The primary efficacy endpoint is the natural log transformation of the seizure frequency per 4 weeks. The primary efficacy analysis was based on results for the ITT population during the 12-week maintenance period. Seizure frequency was compared between each active treatment group and the placebo group using an ANCOVA model with treatment as a factor and seizure frequency as a covariate

Secondary Outcome Measures

Name	Time	Method