Clinical trial NCT00957372: Efficacy and Safety of Eslicarbazepine Acetate as Adjunctive Therapy for Refractory Partial Epilepsy
Official title: Efficacy and Safety of BIA 2-093 as Adjunctive Therapy for Refractory Partial Seizures in a Double-blind, Randomized, Placebo-controlled, Parallel-group, Multicenter Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Partial Epilepsy
Keywords: epilepsy
Lead sponsor: Bial - Portela C S.A.
Sponsor class: INDUSTRY
First posted: 2009-08-12
Enrollment: 253
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Seizure Frequency
timeFrame: 12 weeks
measure: PART II: Nº of Treatment-Emergent Adverse Events (TEAE)
timeFrame: 1-year
Secondary outcomes:
Other outcomes:
Locations:
city: S. Mamede do Coronado
country: Portugal
facility: Bial - Portela & Cª, S.A.
Study officials:
affiliation: Hospital Ruber Internacional La Masó 38, Mirasierra 28034 Madrid, Spain
name: Antonio Gil-Nagel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Santo António Largo Prof. Abel Salazar, 4099-001 Porto, Portugal
name: Jose Lopes-Lima, MD
role: PRINCIPAL_INVESTIGATOR
References: