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Trial record 7 of 1433 for:    "Epilepsy" OR "pyridoxal 5'-phosphate-dependent epilepsy"

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

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ClinicalTrials.gov Identifier: NCT02727101
Recruitment Status : Terminated (slow enrollment)
First Posted : April 4, 2016
Last Update Posted : August 29, 2017
Sponsor:
Collaborator:
Eisai Inc.
Information provided by (Responsible Party):
Pavel Klein, Mid-Atlantic Epilepsy and Sleep Center, LLC

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Epilepsy Drug: perampanel Phase 4

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  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: "Rational Polytherapy" Using Perampanel Dual Therapy Anticonvulsant Combination Treatments of Adults With Refractory Focal Epilepsy : a Pilot Study.
Study Start Date : November 2015
Actual Primary Completion Date : July 2017
Actual Study Completion Date : July 2017


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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Fycompa




Primary Outcome Measures :
  1. responder rate [ Time Frame: 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.

  2. seizure freedom rate [ Time Frame: 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

  3. treatment discontinuation rate [ Time Frame: 12 weeks ]
    To evaluate the safety and tolerability of each perampanel+ combination with treatment discontinuation rate as the primary safety/tolerability outcome measure



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02727101


Locations
United States, Maryland
MidAtlantic Epilepsy and Sleep Center
Bethesda, Maryland, United States, 20817
Sponsors and Collaborators
Mid-Atlantic Epilepsy and Sleep Center, LLC
Eisai Inc.
Investigators
Principal Investigator: Pavel Klein, M.B,B.Chir. Mid-Atlantic Epilepsy and Sleep Center

Responsible Party: Pavel Klein, Principle study investigator, Mid-Atlantic Epilepsy and Sleep Center, LLC
ClinicalTrials.gov Identifier: NCT02727101     History of Changes
Other Study ID Numbers: maes 008
First Posted: April 4, 2016    Key Record Dates
Last Update Posted: August 29, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Pavel Klein, Mid-Atlantic Epilepsy and Sleep Center, LLC:
Focal epilepsy, Perampanel

Additional relevant MeSH terms:
Epilepsy
Epilepsies, Partial
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Lamotrigine
Zonisamide
Phenobarbital
Anticonvulsants
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Antioxidants
Protective Agents
Hypnotics and Sedatives
Central Nervous System Depressants
GABA Modulators
GABA Agents
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP3A Inducers