slow enrollment

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.

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.

Inclusion Criteria:

1. Age 18-65
2. 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.
3. Stable dose for at least 30 days of the chosen background AED dose
4. Epilepsy duration for > 2 years
5. 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.
6. Seizure frequency of ≥1/month

Exclusion Criteria:

1. Primary generalized epilepsy
2. Simple partial seizures without motor components or secondary generalization
3. Non-epileptic seizures
4. Progressive neurological disease including growing neoplasm, CNS degenerative disorders including Alzheimer's disease, other forms of dementia
5. 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
6. Change in the dose of any Antiepileptic Drug within 30 days prior to enrollment
7. Psychosis within six months of enrollment.
8. Active drug or alcohol dependence or any other factors that, in the opinion of the site investigators would interfere with adherence to study requirements;
9. Pregnancy
10. Use of any CNS-active investigational drugs within 3 months of enrollment.
11. Inability or unwillingness of subject or legal guardian/representative to give written informed consent.