Efficacy and Safety of Eslicarbazepine Acetate (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
- 402
- 试验地点
- 1
- 主要终点
- Part I: Seizure Frequency
研究概览
简要总结
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.
详细描述
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).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
ESL was supplied in 400-mg and 800-mg tablets
干预措施: eslicarbazepine acetate (Drug)
ESL 800 mg once daily
ESL was supplied in 400-mg and 800-mg tablets
干预措施: eslicarbazepine acetate (Drug)
ESL 1200 mg once daily
ESL was supplied in 400-mg and 800-mg tablets
干预措施: eslicarbazepine acetate (Drug)
placebo
Placebo matching tablets
干预措施: placebo (Drug)
ESL - PART II
During Part II of the study all patients received Eslicarbazepine Acetate (ESL), including those who had been treated with placebo during Part I. ESL was supplied as scored 800 mg tablets; once daily administration by oral route.
干预措施: eslicarbazepine acetate (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 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
次要结局
未报告次要终点