Perampanel for Treatment of Adults With Refractory Focal Epilepsy : a Pilot Study.

"Rational Polytherapy" Using Perampanel Dual Therapy Anticonvulsant Combination Treatments of Adults With Refractory Focal Epilepsy : a Pilot Study.

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.

Study Overview

• Status: Terminated
• Conditions: Epilepsy
• Intervention / Treatment: Drug: perampanel

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Midatlantic Epilepsy and Sleep Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: phenobarbital; After 12 weeks of baseline observation on phenobarbital medication, the treatment with perampanel will introduced as "add on" medication.	Drug: perampanel; Each group of 6 patients will be followed for 12 weeks of baseline observation on baseline medication. Seizure frequency will be counted, using subjects' self-reported seizure diaries. Perampanel will be titrated to 8-12 mg/day, with the final dose determined by side effects and tolerability of Perampanel at 8-12 mg/day doses. Titration will occur at the rate of 2 mg/week or two weeks, as tolerated.; Other Names: Fycompa
Active Comparator: valproate; After 12 weeks of baseline observation on valproate medication, the treatment with perampanel will introduced as "add on" medication.	Drug: perampanel; Each group of 6 patients will be followed for 12 weeks of baseline observation on baseline medication. Seizure frequency will be counted, using subjects' self-reported seizure diaries. Perampanel will be titrated to 8-12 mg/day, with the final dose determined by side effects and tolerability of Perampanel at 8-12 mg/day doses. Titration will occur at the rate of 2 mg/week or two weeks, as tolerated.; Other Names: Fycompa
Active Comparator: lamotrigine; After 12 weeks of baseline observation on lamotrigine medication, the treatment with perampanel will introduced as "add on" medication.	Drug: perampanel; Each group of 6 patients will be followed for 12 weeks of baseline observation on baseline medication. Seizure frequency will be counted, using subjects' self-reported seizure diaries. Perampanel will be titrated to 8-12 mg/day, with the final dose determined by side effects and tolerability of Perampanel at 8-12 mg/day doses. Titration will occur at the rate of 2 mg/week or two weeks, as tolerated.; Other Names: Fycompa
Active Comparator: levetiracetam; After 12 weeks of baseline observation on levetiracetam medication, the treatment with perampanel will introduced as "add on" medication.	Drug: perampanel; Each group of 6 patients will be followed for 12 weeks of baseline observation on baseline medication. Seizure frequency will be counted, using subjects' self-reported seizure diaries. Perampanel will be titrated to 8-12 mg/day, with the final dose determined by side effects and tolerability of Perampanel at 8-12 mg/day doses. Titration will occur at the rate of 2 mg/week or two weeks, as tolerated.; Other Names: Fycompa
Active Comparator: zonisamide; After 12 weeks of baseline observation on zonisamide medication, the treatment with perampanel will introduced as "add on" medication.	Drug: perampanel; Each group of 6 patients will be followed for 12 weeks of baseline observation on baseline medication. Seizure frequency will be counted, using subjects' self-reported seizure diaries. Perampanel will be titrated to 8-12 mg/day, with the final dose determined by side effects and tolerability of Perampanel at 8-12 mg/day doses. Titration will occur at the rate of 2 mg/week or two weeks, as tolerated.; Other Names: Fycompa
Active Comparator: pregabalin; After 12 weeks of baseline observation on pregabaline medication, the treatment with perampanel will introduced as "add on" medication.	Drug: perampanel; Each group of 6 patients will be followed for 12 weeks of baseline observation on baseline medication. Seizure frequency will be counted, using subjects' self-reported seizure diaries. Perampanel will be titrated to 8-12 mg/day, with the final dose determined by side effects and tolerability of Perampanel at 8-12 mg/day doses. Titration will occur at the rate of 2 mg/week or two weeks, as tolerated.; Other Names: Fycompa
Active Comparator: lacosamide; After 12 weeks of baseline observation on lacosasmide medication, the treatment with perampanel will introduced as "add on" medication.	Drug: perampanel; Each group of 6 patients will be followed for 12 weeks of baseline observation on baseline medication. Seizure frequency will be counted, using subjects' self-reported seizure diaries. Perampanel will be titrated to 8-12 mg/day, with the final dose determined by side effects and tolerability of Perampanel at 8-12 mg/day doses. Titration will occur at the rate of 2 mg/week or two weeks, as tolerated.; Other Names: Fycompa
Active Comparator: clobazam; After 12 weeks of baseline observation on clobazam medication, the treatment with perampanel will introduced as "add on" medication.	Drug: perampanel; Each group of 6 patients will be followed for 12 weeks of baseline observation on baseline medication. Seizure frequency will be counted, using subjects' self-reported seizure diaries. Perampanel will be titrated to 8-12 mg/day, with the final dose determined by side effects and tolerability of Perampanel at 8-12 mg/day doses. Titration will occur at the rate of 2 mg/week or two weeks, as tolerated.; Other Names: Fycompa
Active Comparator: ezogabine; After 12 weeks of baseline observation on ezogabine medication, the treatment with perampanel will introduced as "add on" medication.	Drug: perampanel; Each group of 6 patients will be followed for 12 weeks of baseline observation on baseline medication. Seizure frequency will be counted, using subjects' self-reported seizure diaries. Perampanel will be titrated to 8-12 mg/day, with the final dose determined by side effects and tolerability of Perampanel at 8-12 mg/day doses. Titration will occur at the rate of 2 mg/week or two weeks, as tolerated.; Other Names: Fycompa
Active Comparator: eslicarbazepine; After 12 weeks of baseline observation on eslicarbamazepine medication, the treatment with perampanel will introduced as "add on" medication.	Drug: perampanel; Each group of 6 patients will be followed for 12 weeks of baseline observation on baseline medication. Seizure frequency will be counted, using subjects' self-reported seizure diaries. Perampanel will be titrated to 8-12 mg/day, with the final dose determined by side effects and tolerability of Perampanel at 8-12 mg/day doses. Titration will occur at the rate of 2 mg/week or two weeks, as tolerated.; Other Names: Fycompa
Active Comparator: topiramate; After 12 weeks of baseline observation on eslicarbamazepine medication, the treatment with perampanel will introduced as "add on" medication.	Drug: perampanel; Each group of 6 patients will be followed for 12 weeks of baseline observation on baseline medication. Seizure frequency will be counted, using subjects' self-reported seizure diaries. Perampanel will be titrated to 8-12 mg/day, with the final dose determined by side effects and tolerability of Perampanel at 8-12 mg/day doses. Titration will occur at the rate of 2 mg/week or two weeks, as tolerated.; Other Names: Fycompa
Active Comparator: tiagabine; After 12 weeks of baseline observation on eslicarbamazepine medication, the treatment with perampanel will introduced as "add on" medication.	Drug: perampanel; Each group of 6 patients will be followed for 12 weeks of baseline observation on baseline medication. Seizure frequency will be counted, using subjects' self-reported seizure diaries. Perampanel will be titrated to 8-12 mg/day, with the final dose determined by side effects and tolerability of Perampanel at 8-12 mg/day doses. Titration will occur at the rate of 2 mg/week or two weeks, as tolerated.; Other Names: Fycompa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
responder rate	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.	12 weeks
seizure freedom rate	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	12 weeks
treatment discontinuation rate	To evaluate the safety and tolerability of each perampanel+ combination with treatment discontinuation rate as the primary safety/tolerability outcome measure	12 weeks

Collaborators and Investigators

• Sponsor: Mid-Atlantic Epilepsy and Sleep Center, LLC
• Collaborators: Eisai Inc.
• Investigators: Principal Investigator: Pavel Klein, M.B,B.Chir., Mid-Atlantic Epilepsy and Sleep Center

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): July 1, 2017

Study Registration Dates

• First Submitted: March 29, 2016
• First Submitted That Met QC Criteria: March 29, 2016
• First Posted (Estimate): April 4, 2016

Study Record Updates

• Last Update Posted (Actual): August 29, 2017
• Last Update Submitted That Met QC Criteria: August 28, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Focal epilepsy, Perampanel
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Epilepsies, Partial
• Other Study ID Numbers: maes 008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided