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

Bial - Portela C S.A.402 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

402

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Part I: Seizure Frequency

The primary efficacy endpoint is the natural log transformation of the seizure frequency per 4 weeks. The primary efficacy analysis was based on the intention-to-treat (ITT) population. Efficacy analyses were performed chiefly using data from the 12-week maintenance period in Part I of the study. The primary efficacy variable is the ln transformation of the seizure frequency per 4 weeks. Seizure frequency was compared between each active treatment group and the placebo group using an ANCOVA that models seizure frequency as a function of baseline seizure frequency and treatment.to a "frequency per 4 weeks" basis

Time frame: 12-week maintenance period

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes