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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 395
- 试验地点
- 1
- 主要终点
- PART I - Seizure Frequency
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
ESL 400 mg once daily
Eslicarbazepine acetate (ESL) was supplied in 400 mg tablets for Part I
干预措施: eslicarbazepine acetate (Drug)
ESL 800 mg once daily
Eslicarbazepine acetate (ESL) was supplied in 800-mg tablets for Part I
干预措施: eslicarbazepine acetate (Drug)
ESL 1200 mg once daily
Eslicarbazepine acetate (ESL) was supplied in 400-mg and 800-mg tablets for Part I
干预措施: eslicarbazepine acetate (Drug)
placebo
Placebo tablets matching the 400-mg and 800-mg active substance tablets were supplied
干预措施: placebo (Drug)
ESL - Part II
All patients in Part II (Open-label Extension ) received ESL on an open-label basis, starting at 800 mg once daily.
干预措施: ESL - Part II (Drug)
结局指标
主要结局
PART I - Seizure Frequency
时间窗: 12-week maintenance period
The primary efficacy endpoint is the natural log transformation of the seizure frequency per 4 weeks. The primary efficacy analysis was based on the 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.
PART II - Nº of Treatment-Emergent Adverse Events (TEAE)
时间窗: 1 year
Safety assessments were based primarily on AEs (Number of patients who experienced at least one AEs), and on whether these were related to the study medication, were serious, led to permanent discontinuation of study participation, or led to death.
次要结局
未报告次要终点