"Rational Polytherapy" Using Perampanel Dual Therapy Anticonvulsant Combination Treatments of Adults With Refractory Focal Epilepsy : a Pilot Study.
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- treatment discontinuation rate
研究概览
简要总结
The goal of the present study is to evaluate ("screen") a large number (12) of different dual therapies of perampanel + another AED ("PMP+") for a large, 75-100% seizure frequency reduction. The design of the study will differ from usual AED studies. The study will be (i) open label, with (ii) a small n per group, n=6, with (iii) outcome measures a 'blockbuster effect': (a) ≥75 seizure frequency reduction; and (b) seizure freedom.
详细描述
Investigators will compare rates of seizure freedom and >75% seizure frequency reduction among 12 treatment arms consisting of 6 subjects each with refractory focal epilepsy treated with perampanel and one other AED ("PMP+"). Treatment arms will include (1) Perampanel +phenobarbital, (2) PMP+valproate, (3) PMP+ lamotrigine, (4) PMP + topiramate, (5) PMP + tiagabine, (6) PMP + levetiracetam, (7) PMP + zonisamide, (8) PMP + pregabalin, (9) PMP + lacosamide, (10) PMP+ clobazam, (11) PMP + ezogabine; and (12) PMP + eslicarbazepine. Each group of 6 will be followed for 12 weeks of baseline observation on baseline medication. Seizure frequency will be counted, using subjects' self-reported seizure diaries. PMP will be titrated to 8-12 mg/day, with the final dose determined by side effects and tolerability of PMP at 8-12 mg/day doses. Titration will occur at the rate of 2 mg/week or two weeks (in accordance with FDA labeling), as tolerated. Subjects will be observed for 12 weeks of maintenance treatment on the target PMP doses. Seizure frequency will be compared between the 12 weeks of baseline observation and 12 weeks of maintenance treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Stable focal epilepsy, with partial complex seizures including partial complex seizures with or without secondary generalization, partial simple seizures with a clear motor component with or without secondary generalization, and partial simple seizures with secondary generalization.
- •Stable dose for at least 30 days of the chosen background AED dose
- •Epilepsy duration for > 2 years
- •Past/current treatment with > 4 AEDs. Vagal nerve stimulator treatment will be allowed and will not count as an AED. VNS setting must be stable for 3 months prior to enrollment.
- •Seizure frequency of ≥1/month
排除标准
- •Primary generalized epilepsy
- •Simple partial seizures without motor components or secondary generalization
- •Non-epileptic seizures
- •Progressive neurological disease including growing neoplasm, CNS degenerative disorders including Alzheimer's disease, other forms of dementia
- •Any systemic illness or unstable medical condition that might pose additional risk, including renal or liver disease, clinically uncontrolled cardiac disease, other unstable metabolic or endocrine disturbances, and active systemic cancer
- •Change in the dose of any Antiepileptic Drug within 30 days prior to enrollment
- •Psychosis within six months of enrollment.
- •Active drug or alcohol dependence or any other factors that, in the opinion of the site investigators would interfere with adherence to study requirements;
- •Use of any CNS-active investigational drugs within 3 months of enrollment.
- •Inability or unwillingness of subject or legal guardian/representative to give written informed consent.
研究组 & 干预措施
phenobarbital
After 12 weeks of baseline observation on phenobarbital medication, the treatment with perampanel will introduced as "add on" medication.
干预措施: perampanel (Drug)
valproate
After 12 weeks of baseline observation on valproate medication, the treatment with perampanel will introduced as "add on" medication.
干预措施: perampanel (Drug)
lamotrigine
After 12 weeks of baseline observation on lamotrigine medication, the treatment with perampanel will introduced as "add on" medication.
干预措施: perampanel (Drug)
levetiracetam
After 12 weeks of baseline observation on levetiracetam medication, the treatment with perampanel will introduced as "add on" medication.
干预措施: perampanel (Drug)
zonisamide
After 12 weeks of baseline observation on zonisamide medication, the treatment with perampanel will introduced as "add on" medication.
干预措施: perampanel (Drug)
pregabalin
After 12 weeks of baseline observation on pregabaline medication, the treatment with perampanel will introduced as "add on" medication.
干预措施: perampanel (Drug)
lacosamide
After 12 weeks of baseline observation on lacosasmide medication, the treatment with perampanel will introduced as "add on" medication.
干预措施: perampanel (Drug)
clobazam
After 12 weeks of baseline observation on clobazam medication, the treatment with perampanel will introduced as "add on" medication.
干预措施: perampanel (Drug)
ezogabine
After 12 weeks of baseline observation on ezogabine medication, the treatment with perampanel will introduced as "add on" medication.
干预措施: perampanel (Drug)
eslicarbazepine
After 12 weeks of baseline observation on eslicarbamazepine medication, the treatment with perampanel will introduced as "add on" medication.
干预措施: perampanel (Drug)
topiramate
After 12 weeks of baseline observation on eslicarbamazepine medication, the treatment with perampanel will introduced as "add on" medication.
干预措施: perampanel (Drug)
tiagabine
After 12 weeks of baseline observation on eslicarbamazepine medication, the treatment with perampanel will introduced as "add on" medication.
干预措施: perampanel (Drug)
结局指标
主要结局
treatment discontinuation rate
时间窗: 12 weeks
To evaluate the safety and tolerability of each perampanel+ combination with treatment discontinuation rate as the primary safety/tolerability outcome measure
responder rate
时间窗: 12 weeks
responder rate, defined by \>75% seizure frequency reduction. Average seizure frequency per 4 weeks will be compared between the 12 weeks of "PMP+" maintenance treatment and 12 weeks of baseline.
seizure freedom rate
时间窗: 12 weeks
seizure freedom rate. Proportion of responders and of subjects with seizure freedom in each treatment arm will be compared with historical data of 75% seizure reduction from pivotal phase 3 studies for which such data is publicly available
次要结局
未报告次要终点
研究者
Pavel Klein
Principle study investigator
Mid-Atlantic Epilepsy and Sleep Center, LLC