A Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel-group Study to Evaluate the Efficacy and Safety of Adjunctive Brivaracetam in Subjects (>=16 to 80 Years of Age) With Partial Seizures With or Without Secondary Generalization
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 449
- 试验地点
- 94
- 主要终点
- Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
The purpose of the study is to evaluate the efficacy of brivaracetam (BRV) compared to placebo (PBO) as adjunctive treatment in subjects (>=16 to 80 years of age) with partial seizures with or without secondary generalization despite current treatment with 1 or 2 concomitant antiepileptic drugs (AEDs) and to assess the safety and tolerability of BRV in subjects >= 16 years to 80 years of age.
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
- 16 Years 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects (male or female) from 16 to 80 years of age at Visit 1, both inclusive
- •Female subjects with childbearing potential are eligible if they use a medically accepted contraceptive method
- •Subjects having at least 8 partial seizures (according to the 1981 ILAE classification) during the 8-Week Baseline Period with at least 2 partial seizures during each 4-week interval of the Baseline Period
- •Subjects having at least 2 partial seizures whether or not secondary generalization per month during the 3 months preceding Visit 1
- •Subjects uncontrolled while treated by 1 or 2 permitted concomitant antiepileptic drug [AED](s). Vagal Nerve Stimulation (VNS) is allowed and will be counted as a concomitant AED
排除标准
- •Subject has history or presence of status epilepticus during the year preceding Visit 1 or during Baseline
- •Subject is currently treated with levetiracetam
- •Subject has taken levetiracetam within 90 days prior to Visit 1
研究组 & 干预措施
Placebo
- 12 weeks Treatment Period: Subjects will receive Placebo
- 4 weeks Down-Titration Period: Subjects will receive Placebo
干预措施: Placebo (Drug)
BRV 50 mg/day
12 weeks Treatment Period: Subjects will receive BRV 50 mg/day
- Subjects entering into the Long term follow up (LTFU) study or managed access program (MAP): 2 weeks Transition Period: Subjects will receive BRV 50 mg/day followed by LTFU or MAP: Subjects will receive BRV 100 mg/day
- Subjects not entering into the LTFU study or MAP: 4 weeks Down-Titration Period: Subjects will receive BRV 25 mg/day for 1 week followed by Placebo for 3 weeks, followed by a Study Drug-Free Period
干预措施: Placebo (Drug)
BRV 50 mg/day
12 weeks Treatment Period: Subjects will receive BRV 50 mg/day
- Subjects entering into the Long term follow up (LTFU) study or managed access program (MAP): 2 weeks Transition Period: Subjects will receive BRV 50 mg/day followed by LTFU or MAP: Subjects will receive BRV 100 mg/day
- Subjects not entering into the LTFU study or MAP: 4 weeks Down-Titration Period: Subjects will receive BRV 25 mg/day for 1 week followed by Placebo for 3 weeks, followed by a Study Drug-Free Period
干预措施: Brivaracetam (Drug)
BRV 200 mg/day
12 weeks Treatment Period: Subjects will receive BRV 200 mg/day
- Subjects entering into the Long term follow up (LTFU) study or managed access program (MAP): 2 weeks Transition Period: Subjects will receive BRV 150 mg/day followed by LTFU or MAP: Subjects will receive BRV 100 mg/day
- Subjects not entering into the LTFU study or MAP: 4 weeks Down-Titration Period: Subjects will receive BRV 150 mg/day for 1 week followed by BRV 100 mg/day for 1 week, followed by BRV 50 mg/day for 1 week, followed by BRV 25 mg/day for 1 week followed by a Study Drug-Free Period
干预措施: Placebo (Drug)
BRV 200 mg/day
12 weeks Treatment Period: Subjects will receive BRV 200 mg/day
- Subjects entering into the Long term follow up (LTFU) study or managed access program (MAP): 2 weeks Transition Period: Subjects will receive BRV 150 mg/day followed by LTFU or MAP: Subjects will receive BRV 100 mg/day
- Subjects not entering into the LTFU study or MAP: 4 weeks Down-Titration Period: Subjects will receive BRV 150 mg/day for 1 week followed by BRV 100 mg/day for 1 week, followed by BRV 50 mg/day for 1 week, followed by BRV 25 mg/day for 1 week followed by a Study Drug-Free Period
干预措施: Brivaracetam (Drug)
结局指标
主要结局
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
时间窗: From start of the Treatment Period (Week 0) until Safety Visit (up to Week 18); only for OLTP- From last visit of Transition Period to beginning of MAP (up to 4 Years 10 Months)
An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. Treatment-Emergent AEs were defined as AEs which had onset on or after the first dose of IMP. As per planned analysis, safety data for all study periods was combined excluding Open-Label Temporary period.
Percentage of Participants With Treatment-Emergent AEs (TEAEs) Leading to Study Withdrawal
时间窗: From start of the Treatment Period (Week 0) until Safety Visit (up to Week 18); only for OLTP- From last visit of Transition Period to beginning of MAP (up to 4 Years 10 Months)
An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. Treatment-Emergent AEs were defined as AEs which had onset on or after the first dose of IMP. As per planned analysis, safety data for all study periods was combined excluding Open-Label Temporary period.
Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)
时间窗: From start of the Treatment Period (Week 0) until Safety Visit (up to Week 18); only for OLTP- From last visit of Transition Period to beginning of MAP (up to 4 Years 10 Months)
Serious Adverse event (SAE) was defined as any events which: • results in death, • is life-threatening threatening (note that this did not include a reaction that might have caused death had it occurred in a more severe form.), •results in significant or persistent disability/incapacity, • results in a congenital anomaly/birth defect (including that occurring in a fetus), • results in Important medical event that, based upon appropriate medical judgment, may jeopardize the participant and might require medical or surgical intervention to prevent 1 of the other outcomes listed here, and • results in initial inpatient hospitalization or prolongation of hospitalization. As per planned analysis, safety data for all study periods was combined excluding Open-Label Temporary period.
Partial Seizure Frequency Per 28 Days During the 12-week Treatment Period
时间窗: From Baseline to 12-week Treatment Period
According to International League Against Epilepsy (ILAE) classification (1981), seizures were classified as type IA (IA1, IA2, IA3, and IA4), IB, IC, II (IIA, IIB, IIC, IID, IIE, and IIF) or III. 28 day adjusted seizure frequency for partial seizures (seizure types IA+IB+IC) was calculated for treatment period by dividing the number of partial seizures by the number of days for which the DRC was completed for treatment period and multiplying the resulting value by 28.
次要结局
- Time to 10th Partial Seizure During the 12-week Treatment Period(During the 12-week Treatment Period)
- Brivaracetam Plasma Concentration(Plasma samples were collected at >0-4hours, >4-8hours, >8hours in weeks 2, 4, 8, 12, and 14)
- Percentage of Participants With Categorized Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period(From Baseline to 12-week Treatment Period)
- All Seizure Frequency (Partial, Generalized, and Unclassified Epileptic Seizures) Per 28 Days During the 12-week Treatment Period(During the 12-week Treatment Period)
- 50% Responder Rate Based on Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period(From Baseline to 12-week Treatment Period)
- Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period(From Baseline to 12-week Treatment Period)
- Time to 1st Partial Seizure During the 12-week Treatment Period(During the 12-week Treatment Period)
- Percentage of Participants Who Are Seizure Free (Partial, All Epileptic Seizures) During the 12-week Treatment Period(During the 12-week Treatment Period)
- Time to 5th Partial Seizure During the 12-week Treatment Period(During the 12-week Treatment Period)