Efficacy and Safety of BIA 2-093 as Adjunctive Therapy for Refractory Partial Seizures in a Double-blind, Randomized, Placebo-controlled, Parallel-group, Multicenter Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 253
- 试验地点
- 1
- 主要终点
- PART II: Nº of Treatment-Emergent Adverse Events (TEAE)
研究概览
简要总结
The primary objective was to evaluate the efficacy of eslicarbazepine acetate (ESL) administered once daily at 1200 mg or 800 mg, compared with placebo as adjunctive therapy in patients with refractory partial epilepsy over a 12-week maintenance period.
详细描述
This was a phase III, 2-part multicenter study. Part I was an 26-week parallel-group, randomized, placebo-controlled design consisting of an 8 week baseline period, a 2 week double-blinded titration period, 12 week maintenance period, and a 4 week tapering-off period. After completing the baseline period, patients were randomized in a 1:1:1 ratio to 1 of the 2 ESL daily dose levels (1200 or 800 mg) or placebo.
Part II was a 1-year open-label extension for patients who had completed Part I. Starting at 800 mg/day, the dosage could be titrated at 400 mg intervals down to a minimum of 400 mg/day or up to a maximum of 1200 mg/day. Patients who completed Part II could participate in a study extension and continue treatment with ESL until marketing authorization is obtained or clinical development is discontinued, with visits scheduled at the discretion of the investigator but at least every 6 months.
Results from Part I & II were presented in two separate reports.
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 1200 mg daily (Part I)
ESL 1200mg daily
干预措施: eslicarbazepine acetate (Drug)
ESL 800 mg daily (Part I)
ESL 800mg daily
干预措施: eslicarbazepine acetate (Drug)
placebo (Part I)
placebo
干预措施: placebo (Part I) (Drug)
ESL - Open-label Extension (Part II)
All patients were treated with only ESL during Part II.
干预措施: ESL - Open-label Extension (Part II) (Drug)
结局指标
主要结局
PART II: Nº of Treatment-Emergent Adverse Events (TEAE)
时间窗: 1-year
The primary objective for Part II of the study was to evaluate the safety and tolerability of eslicarbazepine acetate (ESL, BIA 2-093) at doses titrated to an efficacy or safety endpoint over a 1-year open-label period. Safety assessments were based primarily on AEs (Number of participants with at least one treatment-emergent adverse events are reported); assessment of AEs was based on treatment relatedness, action taken on study drug, outcome, and causality.
Seizure Frequency
时间窗: 12 weeks
The primary efficacy endpoint is the natural log transformation of the seizure frequency per 4 weeks. The primary efficacy analysis was based on results for the ITT population during the 12-week maintenance period. Seizure frequency was compared between each active treatment group and the placebo group using an ANCOVA model with treatment as a factor and seizure frequency as a covariate
次要结局
未报告次要终点