effects of eslicarbazepine acetate (esl, bia 2-093) on cognitive function in children with partial onset seizures

Conditions: Partial Epilepsy

Summary: to evaluate the effects of eslicarbazepine acetate on cognition in comparison with placebo as adjunctive therapy in children aged 6 to 16 years old with refractory partial-onset seizures.

this will be a 2-part multicentre study in approximately 117 patients. part i of the study will consist of a 4-week prospective observational baseline period, a 12-week double-blind period (4-week up-titration and 8-week maintenance), and a tapering-off period. after the screening visit (v1), patients will enter the baseline period. at the end of the baseline period (v2), eligible patients will be randomised in a ratio of 2:1 to receive double-blind treatment with eslicarbazepine acetate or placebo in addition to concomitant therapy with 1 or 2 anti-epileptic drugs (aeds). concomitant aed therapy will be kept stable during the whole study. initial dose of the study treatment will be 10 mg/kg/day. after 2-weeks on 10 mg/kg/day, the dose will be up-titrated to 20 mg/kg/day (maximum 1200 mg/day). after 2 weeks on 20 mg/kg/day, dose will be up-titrated to 30 mg/kg/day (maximum 1200 mg/day) and patients will receive this dose for 8 weeks. if intolerable adverse events (aes) occur, the patient can be down-titrated to the previous dose (only 1 down-titration step will be allowed) or discontinued. after the 8-week maintenance period, the study treatment will be tapered off in 10 mg/kg/day 2 week steps. however, if a patient experiences an increase in seizure frequency (e.g. more than 100% increase vs. baseline) during tapering-off, the patient can proceed directly to the open-label part of the study (part ii). after completion of the last 2-week 10 mg/kg/day step, patients will have the option to enter a 1 year open-label treatment (part ii) with eslicarbazepine acetate (up to 30 mg/kg/day, maximum 1200 mg/day), or will have a 4 week observational follow-up period.

Eligibility criteria:
inclusion criteria: at visit 1 (screening), patient must be/have: * written informed consent by parent or legal guardian and, where applicable, the patient; * age 6 to 16 years, inclusive; * a documented diagnosis of epilepsy for at least 12 months prior to screening; * at least 2 partial onset seizures during the 4 weeks prior to screening despite treatment with 1 to 2 aeds in a stable dose regimen; * an intelligence quotient (iq) of at least 70; * current treatment with 1 to 2 aeds (except oxcarbazepine, benzodiazepines other than clobazam and vagus nerve stimulation (vns)); * excepting epilepsy, patient is judged to be in general good health based on medical history, physical examination and clinical laboratory tests; * in the opinion of the investigator, able to complete the cognitive drug research (cdr) test battery; * in case of a girl of childbearing potential, patient presents a serum b-human chorionic gonadotropin (b hcg) test consistent with a non gravid state and agrees to remain abstinent or use reliable contraception (if used, hormonal contraception must be combined with a barrier method) starting at screening and continuing until at least the post-study visit (psv). at visit 2 (randomisation), patient must be/have: * at least 2 partial-onset seizures during the 4 week baseline period prior to randomisation (documented in a diary); * in case of a girl of childbearing potential, patient presents a urine b-hcg test consistent with a non-gravid state; * stable dose regimen of concomitant aeds during the 4 week baseline period; * diaries satisfactorily completed by the patient or his/her caregiver during the baseline period; * satisfactory compliance with the study requirements during the baseline period. exclusion criteria: at visit 1 (screening), patients must not be/have: * only simple partial seizures with no motor symptomatology; * primarily generalised seizures; * known rapidly progressive neurological disorders (progressive brain disease, epilepsy secondary to progressive cerebral lesion); * occurrence of seizures too close to count accurately; * 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 non-epileptic origin; * lennox-gastaut syndrome; * west syndrome; * major psychiatric disorders; * seizures of psychogenic origin within the last 2 years; * history of schizophrenia or suicide attempt; * history of attention deficit disorder or other diseases adversely affecting cognitive abilities; * currently treated with oxcarbazepine, benzodiazepines other than clobazam (on a routine or chronic basis) and/or vns; * known hypersensitivity to carboxamide derivatives (oxcarbazepine or carbamazepine); * uncontrolled cardiac, renal, hepatic, endocrine, gastrointestinal, metabolic, haematological or oncology disorder; * second or third degree atrioventricular blockade; * relevant clinical laboratory abnormalities; * estimated creatinine clearance (clcr) \<60 ml/min; * pregnancy or nursing; * treatment with eslicarbazepine acetate in any previous study; * participation in other drug clinical trial within the last 2 months; * not ensured capability to perform the trial; * any other condition or circumstance that, in the opinion of the investigator, may compromise the patient's ability to comply with the study protocol. at visit 2 (randomisation), patients must not be / have: • any condition or circumstance that, in the opinion of the investigator, may compromise the patient's ability to comply with the study protocol.

Keywords: partial epilepsy eslicarbazepine acetate children