Clinical trial NCT00957047: Efficacy and Safety Study of BIA 2-093 in Combination With Other Anti-Epileptic Drugs to Treat Partial Epilepsy
Official title: Efficacy and Safety of BIA 2-093 as Adjunctive Therapy for Refractory Partial Seizures in a Double-blind, Randomised, Placebo-controlled, Parallel-group, Multicentre Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Partial Epilepsy
Keywords: refractory
partial
epilepsy
Lead sponsor: Bial - Portela C S.A.
Sponsor class: INDUSTRY
First posted: 2009-08-12
Enrollment: 395
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 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.

Detailed description: 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.

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: PART I - Seizure Frequency
timeFrame: 12-week maintenance period
measure: PART II - Nº of Treatment-Emergent Adverse Events (TEAE)
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Trofa
country: Portugal
facility: Bial - Portela & Cª, S.A.
state: Coronado (S.Romão E S. Mamede)
Study officials:
affiliation: Sahlgren University Hospital, Göteborg, Sweden
name: Elinor Ben-Menachem, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rua Pedro de Toledo 655, Vila Clemento, Sao Paulo, Brazil
name: Alberto Alain Gabbai, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Andermann E, Rosenfeld W, Penovich P, Rogin J, Cendes F, Carreno M, Ramsay RE, Ben-Menachem E, Gama H, Rocha F, Soares-da-Silva P, Tosiello R, Blum D, Grinnell T. Comparative analysis of the safety and tolerability of eslicarbazepine acetate in older (>/=60 years) and younger (18-59 years) adults. Epilepsy Res. 2021 Jan;169:106478. doi: 10.1016/j.eplepsyres.2020.106478. Epub 2020 Oct 10.