efficacy and safety of eslicarbazepine acetate as adjunctive therapy for refractory partial seizures

Conditions: Refractory Partial Epilepsy

Summary: this was a phase iii 4-part study in multiple centres. part i was a 26-week parallel-group, randomised, placebo-controlled period (8 weeks single-blind placebo baseline, 2 weeks double-blind titration, 12 weeks maintenance, and 4 weeks tapering off). after completing the baseline period, patients were randomised in a 1:1:1:1 ratio to 1 of 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. part iii was an additional 1-year open-label extension for patients who had completed part ii, had participated in the post-part ii study extension, which allowed patients to continue treatment with esl, or had continued to take esl in a compassionate use program. esl starting doses were the same as received at the end of part ii, during post-part ii study extension, or under compassionate use, and could be titrated up or down at 400-mg intervals between 400 and 1200 mg once daily. part iv was a study extension to allow patients to continue esl treatment after the end of part iii until marketing authorisation or discontinuation of clinical development.

duration of treatment: the duration of part i was 26 weeks: 8 weeks of placebo run-in, 2 weeks of dose titration, 12 weeks of maintenance, and 4 weeks of tapering-off period. the duration of part ii was 1 year. the duration of part iii was planned to be 1 year (some patients were treated for \>1 year). the duration of part iv was \>3 years (patients could continue treatment with esl until market availability).

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

Keywords: refractory partial epilepsy