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CompletedNCT03288129Updated May 16, 2022Results posted

Study to Evaluate the Efficacy and Safety of Perampanel as Monotherapy or First Adjunctive Therapy in Subjects With Partial Onset Seizures With or Without Secondarily Generalized Seizures or With Primary Generalized Tonic-Clonic Seizures

A Phase 4 interventional study of Perampanel in Partial Onset Seizures, Secondarily Generalized Seizures and Primary Generalized Tonic-Clonic Seizures, sponsored by Eisai Inc.. Completed at 24 sites in United States. Open to participants aged 4 Years and older. Per ClinicalTrials.gov, last updated 2022-05-16.

Sponsored by Eisai Inc. · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
54
Allocation
Not applicable
Ages
4 Years and older
Sex
All
01

Study summary

This study will assess the retention rate of perampanel when given as monotherapy or first adjunctive therapy in participants with partial-onset seizures or primary generalized tonic clonic seizures. The study consists of 4 periods: a Screening Period (to start no earlier than 6 weeks before the first dose of study drug), a Titration Period (up to 13 weeks), a Maintenance Period (39 weeks), and a Follow-Up Period (4 weeks).

02

Conditions studied

  • Partial Onset Seizures
  • Secondarily Generalized Seizures
  • Primary Generalized Tonic-Clonic Seizures

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Keywords

  • monotherapy
  • adjunctive therapy
  • open-label
  • multicenter
03

Who can participate

Ages eligible
4 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Participants will be male or female and no younger than 4 years of age and be able to swallow perampanel tablets.

  • Participants must have a diagnosis of epilepsy with POS with or without SGS or with PGTCS. Either of the following must have occurred to support an epilepsy diagnosis:

    1. At least two unprovoked (or reflex) seizures occurring greater than 24 hours apart
    2. One unprovoked (or reflex) seizure with Electroencephalography (EEG) evidence of seizures
  • Participants who receive perampanel as a first adjunctive therapy must currently have been treated with stable doses of monotherapy with an anti-epileptic drug (AED) for 8 weeks prior to Visit 2 (Week 0), have not previously received adjunctive AED treatment, and must, in the investigator's judgement, be in need of initial adjunctive therapy after failure to control seizures with AED monotherapy, at the optimal dose and duration.
  • Participants who receive perampanel as monotherapy, who were newly diagnosed (treatment naïve), following the defined diagnosis of epilepsy.
  • Participants who are currently receiving monotherapy treatment may receive perampanel as monotherapy if, in the investigator's judgment, the participant may benefit from a change in monotherapy treatment. Participants must not have previously received adjunctive AED treatment.
  • If antidepressants or antianxiety drugs are used, participants must be on a stable dose regimen of these drugs during the 8 weeks before Visit 2 (Week 0).

Exclusion criteria

Exclusion Criteria:

  • Participants should not have previously received or currently be receiving perampanel.
  • Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta human chorionic gonadotropin [β-hCG] or hCG test with a minimum sensitivity of 25 International Units per liter [IU/L] or equivalent units of β-hCG or hCG); a separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.

  • Females of childbearing potential who:

    • Within 28 days before study entry, did not use a highly effective method of contraception, which includes any of the following:

      • Total abstinence (if it is their preferred and usual lifestyle)
      • An intrauterine device or intrauterine hormone-releasing system
      • An oral contraceptive (with additional barrier method if using contraceptive containing levonorgestrel); participant must be on a stable dose of the same oral contraceptive product for at least 28 days before dosing and throughout the study and for 28 days after study drug discontinuation
      • Have a vasectomized partner with confirmed azoospermia
    • Do not agree to use a highly effective method of contraception (as described above) throughout the entire study period and for 28 days after study drug discontinuation For sites outside of the European Union, it is permissible that if a highly effective method of contraception is not appropriate or acceptable to the participant, then the participant must agree to use a medically acceptable method of contraception, i.e, double barrier methods of contraception such as condom plus diaphragm or cervical/vault cap with spermicide.

NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (i.e, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).

  • Presence of or previous history of Lennox-Gastaut syndrome
  • Presence of non-motor simple partial seizures only
  • A history of status epilepticus within 1 year before Screening Visit (Visit 1)
  • Participants on antipsychotics or who have psychotic disorder(s) or unstable recurrent affective disorder(s) with a history of attempted suicide within 1 year before Screening Visit (Visit 1)
  • Presence of a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors
  • Concomitant use of barbiturates (except for seizure control indication and premedication for electroencephalogram) and benzodiazepines (except for seizure control indication) within 8 weeks prior to Visit 2 (Week 0)
  • Use of intermittent rescue benzodiazepines (i.e, 1 to 2 doses over a 24-hour period is considered a one time rescue) 2 or more times in the 8-week period prior to Visit 2 (Week 0)
  • Severe renal insufficiency (defined by estimated glomerular filtration rate of \< 30 milliliters per minute [mL/min]) or participants who receive hemodialysis
  • Evidence of clinically significant disease (eg, cardiac, respiratory, gastrointestinal, renal disease, hepatic disease) that in the opinion of the investigator(s) could affect the participant's safety or study conduct NOTE: Stable elevation of liver enzymes, alanine aminotransferase and aspartate aminotransferase due to concomitant medication(s) will be allowed if they are less than 3 times the upper limits of normal.
  • Hypersensitivity to perampanel or any excipients
  • Participants with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
  • Participants who are participating in other interventional clinical trial
  • Participant who are judged to have inadequate cognitive ability for participation in the study (intelligence quotient \< 80 or investigator judgment)
  • Any suicidal ideation with intent with or without a plan, at the time of or within 6 months of screening, as indicated by answering "Yes" to questions 4 and 5 on the Suicidal Ideation section of the Columbia Suicide Severity Rating Scale (C-SSRS)
  • Any lifetime suicidal behavior based on the C-SSRS
  • Concomitant use of any form of cannabidiol (CBD)
  • Planned brain surgery during study participation
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
54 participants (actual)

Study arms

  • Experimental
    Perampanel

    Perampanel will be administered orally once daily (QD) at bedtime. At the beginning of the Titration Period, oral perampanel will start at a dose of 2 milligrams (mg) QD. Doses of perampanel will then be up titrated in increments of 2 mg at no less than 2-week intervals according to the investigator's judgment. At the 4 mg dose, the investigator will confirm whether further dose escalation is needed based on participant response and tolerability. The investigator may adjust dosing further or leave the participant at 4 mg. The maximum dose is 12 mg. During the 39-week Maintenance Period, participants will continue to receive the perampanel dose level that was administered at the end of the Titration Period.

    Drug: Perampanel

Interventions

  • DrugPerampanel

    film-coated tablets

    Also known as: Fycompa, E2007

05

What researchers measure

Primary outcomes

  1. Percentage of Participants Remaining on Perampanel Treatment at 3 Months After the Initiation of Treatment

    The retention rate was defined as the percentage of participants remaining on perampanel treatment at 3 months after the initiation of treatment.

    Time frame: Month 3

  2. Percentage of Participants Remaining on Perampanel Treatment at 6 Months After the Initiation of Treatment

    The retention rate was defined as the percentage of participants remaining on perampanel treatment at 6 months after the initiation of treatment.

    Time frame: Month 6

  3. Percentage of Participants Remaining on Perampanel Treatment at 9 Months After the Initiation of Treatment

    The retention rate was defined as the percentage of participants remaining on perampanel treatment at 9 months after the initiation of treatment.

    Time frame: Month 9

  4. Percentage of Participants Remaining on Perampanel Treatment at 12 Months After the Initiation of Treatment

    The retention rate was defined as the percentage of participants remaining on perampanel treatment at 12 months after the initiation of treatment.

    Time frame: Month 12

Secondary outcomes

  1. Percentage of Participants Who Achieved Seizure-free Status During the Maintenance Period

    Seizure-free status was defined as no incidence of seizure during the entire maintenance period. Partial seizures: when abnormal electrical activity begins in only one part of brain include (1) simple partial seizures: participants does not lose consciousness may experience muscle jerking or stiffening, (2) complex partial seizures: participant loses awareness. SGS: disturbances that spread to both sides of brain after partial seizure has already begun and happen when burst of electrical activity in limited area (the partial seizure) spreads throughout brain. PGTCS: disturbances in functioning of both sides of brain that caused by electrical signals spreading through brain inappropriately.

    Time frame: Up to 39 weeks of Maintenance Period

  2. Percentage of Participants Who Achieved 3-month Seizure-free Status During the Maintenance Period

    Seizure-free status was defined as no incidence of seizure at 3 months during the Maintenance Period. Partial seizures: when abnormal electrical activity begins in only one part of brain include (1) simple partial seizures: participant does not lose consciousness may experience muscle jerking or stiffening, (2) complex partial seizures: participant loses awareness. SGS: disturbances that spread to both sides of brain after partial seizure has already begun and happen when burst of electrical activity in limited area (the partial seizure) spreads throughout brain. PGTCS: disturbances in functioning of both sides of brain that caused by electrical signals spreading through brain inappropriately.

    Time frame: Up to 3 months of Maintenance Period

  3. Percentage of Participants Who Achieved 6-month Seizure-free Status During the Maintenance Period

    Seizure-free status was defined as no incidence of seizure at 6 months during Maintenance Period. Partial seizures: when abnormal electrical activity begins in only one part of brain include (1) simple partial seizures: participant does not lose consciousness may experience muscle jerking or stiffening, (2) complex partial seizures: participant loses awareness. SGS: disturbances that spread to both sides of brain after partial seizure has already begun and happen when burst of electrical activity in limited area (the partial seizure) spreads throughout brain. PGTCS: disturbances in functioning of both sides of brain that caused by electrical signals spreading through brain inappropriately.

    Time frame: Up to 6 months of Maintenance Period

  4. Percentage of Participants Who Received Perampanel as a First Adjunctive Therapy and Converted to Perampanel Monotherapy

    Percentage of participants who received perampanel as a first adjunctive therapy and converted to perampanel monotherapy were reported.

    Time frame: Up to 52 weeks

  5. Number of Participants With Treatment-emergent Adverse Events (TEAE)

    A TEAE was defined as an adverse event (AE) that emerged during treatment, having been absent at pretreatment (Baseline) or reemerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous.

    Time frame: From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)

  6. Number of Participants With Treatment-emergent Serious Adverse Events (SAE)

    A SAE was defined as any untoward medical occurrence that at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect. A TEAE was defined as an event that emerges during treatment having been absent pre-treatment, or worsens relative to the pre-treatment state.

    Time frame: From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)

06

Results

Posted May 16, 2022

Participant flow

Participants took part in the study at 14 investigative sites in the United States from 23 August 2017 to 27 April 2021.

Participant flow — Overall Study
MilestonePerampanel 12 mg
Started54
Completed32
Not completed22
Withdrew: Adverse event10
Withdrew: Lost to follow-up3
Withdrew: Withdrawal by subject3
Withdrew: Withdrawal of consent/assent1
Withdrew: Other5

Outcome measures

PrimaryPercentage of Participants Remaining on Perampanel Treatment at 3 Months After the Initiation of Treatment

The retention rate was defined as the percentage of participants remaining on perampanel treatment at 3 months after the initiation of treatment.

Time frame:
Month 3
Reported as:
Number · percentage of participants
Percentage of Participants Remaining on Perampanel Treatment at 3 Months After the Initiation of Treatment
percentage of participantsPerampanel 12 mg
Percentage of Participants Remaining on Perampanel Treatment at 3 Months After the Initiation of Treatment85.2
PrimaryPercentage of Participants Remaining on Perampanel Treatment at 6 Months After the Initiation of Treatment

The retention rate was defined as the percentage of participants remaining on perampanel treatment at 6 months after the initiation of treatment.

Time frame:
Month 6
Reported as:
Number · percentage of participants
Percentage of Participants Remaining on Perampanel Treatment at 6 Months After the Initiation of Treatment
percentage of participantsPerampanel 12 mg
Percentage of Participants Remaining on Perampanel Treatment at 6 Months After the Initiation of Treatment68.5
PrimaryPercentage of Participants Remaining on Perampanel Treatment at 9 Months After the Initiation of Treatment

The retention rate was defined as the percentage of participants remaining on perampanel treatment at 9 months after the initiation of treatment.

Time frame:
Month 9
Reported as:
Number · percentage of participants
Percentage of Participants Remaining on Perampanel Treatment at 9 Months After the Initiation of Treatment
percentage of participantsPerampanel 12 mg
Percentage of Participants Remaining on Perampanel Treatment at 9 Months After the Initiation of Treatment63.0
PrimaryPercentage of Participants Remaining on Perampanel Treatment at 12 Months After the Initiation of Treatment

The retention rate was defined as the percentage of participants remaining on perampanel treatment at 12 months after the initiation of treatment.

Time frame:
Month 12
Reported as:
Number · percentage of participants
Percentage of Participants Remaining on Perampanel Treatment at 12 Months After the Initiation of Treatment
percentage of participantsPerampanel 12 mg
Percentage of Participants Remaining on Perampanel Treatment at 12 Months After the Initiation of Treatment51.9
SecondaryPercentage of Participants Who Achieved Seizure-free Status During the Maintenance Period

Seizure-free status was defined as no incidence of seizure during the entire maintenance period. Partial seizures: when abnormal electrical activity begins in only one part of brain include (1) simple partial seizures: participants does not lose consciousness may experience muscle jerking or stiffening, (2) complex partial seizures: participant loses awareness. SGS: disturbances that spread to both sides of brain after partial seizure has already begun and happen when burst of electrical activity in limited area (the partial seizure) spreads throughout brain. PGTCS: disturbances in functioning of both sides of brain that caused by electrical signals spreading through brain inappropriately.

Time frame:
Up to 39 weeks of Maintenance Period
Reported as:
Number · percentage of participants
Percentage of Participants Who Achieved Seizure-free Status During the Maintenance Period
percentage of participantsPerampanel 12 mg
Percentage of Participants Who Achieved Seizure-free Status During the Maintenance Period19.2
SecondaryPercentage of Participants Who Achieved 3-month Seizure-free Status During the Maintenance Period

Seizure-free status was defined as no incidence of seizure at 3 months during the Maintenance Period. Partial seizures: when abnormal electrical activity begins in only one part of brain include (1) simple partial seizures: participant does not lose consciousness may experience muscle jerking or stiffening, (2) complex partial seizures: participant loses awareness. SGS: disturbances that spread to both sides of brain after partial seizure has already begun and happen when burst of electrical activity in limited area (the partial seizure) spreads throughout brain. PGTCS: disturbances in functioning of both sides of brain that caused by electrical signals spreading through brain inappropriately.

Time frame:
Up to 3 months of Maintenance Period
Reported as:
Number · percentage of participants
Percentage of Participants Who Achieved 3-month Seizure-free Status During the Maintenance Period
percentage of participantsPerampanel 12 mg
Percentage of Participants Who Achieved 3-month Seizure-free Status During the Maintenance Period34.6
SecondaryPercentage of Participants Who Achieved 6-month Seizure-free Status During the Maintenance Period

Seizure-free status was defined as no incidence of seizure at 6 months during Maintenance Period. Partial seizures: when abnormal electrical activity begins in only one part of brain include (1) simple partial seizures: participant does not lose consciousness may experience muscle jerking or stiffening, (2) complex partial seizures: participant loses awareness. SGS: disturbances that spread to both sides of brain after partial seizure has already begun and happen when burst of electrical activity in limited area (the partial seizure) spreads throughout brain. PGTCS: disturbances in functioning of both sides of brain that caused by electrical signals spreading through brain inappropriately.

Time frame:
Up to 6 months of Maintenance Period
Reported as:
Number · percentage of participants
Percentage of Participants Who Achieved 6-month Seizure-free Status During the Maintenance Period
percentage of participantsPerampanel 12 mg
Percentage of Participants Who Achieved 6-month Seizure-free Status During the Maintenance Period23.1
SecondaryPercentage of Participants Who Received Perampanel as a First Adjunctive Therapy and Converted to Perampanel Monotherapy

Percentage of participants who received perampanel as a first adjunctive therapy and converted to perampanel monotherapy were reported.

Time frame:
Up to 52 weeks
Reported as:
Number · percentage of participants
Percentage of Participants Who Received Perampanel as a First Adjunctive Therapy and Converted to Perampanel Monotherapy
percentage of participantsPerampanel 12 mg
Percentage of Participants Who Received Perampanel as a First Adjunctive Therapy and Converted to Perampanel Monotherapy28.8
SecondaryNumber of Participants With Treatment-emergent Adverse Events (TEAE)

A TEAE was defined as an adverse event (AE) that emerged during treatment, having been absent at pretreatment (Baseline) or reemerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous.

Time frame:
From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)
Reported as:
Count of participants · Participants
Number of Participants With Treatment-emergent Adverse Events (TEAE)
ParticipantsPerampanel 12 mg
Number of Participants With Treatment-emergent Adverse Events (TEAE)48
SecondaryNumber of Participants With Treatment-emergent Serious Adverse Events (SAE)

A SAE was defined as any untoward medical occurrence that at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect. A TEAE was defined as an event that emerges during treatment having been absent pre-treatment, or worsens relative to the pre-treatment state.

Time frame:
From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks)
Reported as:
Count of participants · Participants
Number of Participants With Treatment-emergent Serious Adverse Events (SAE)
ParticipantsPerampanel 12 mg
Number of Participants With Treatment-emergent Serious Adverse Events (SAE)4

Adverse events

Collected over From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Perampanel 12 mg1/54 (1.9%)4/54 (7.4%)47/54 (87%)
Most frequent serious events
Most frequent serious events
EventPerampanel 12 mg
Sudden unexplained death in epilepsyGeneral disorders1/54
Transient ischaemic attackNervous system disorders1/54
DepressionPsychiatric disorders1/54
Mental status changesPsychiatric disorders1/54
Suicidal ideationPsychiatric disorders1/54
Most frequent other events
Showing 10 of 15
Most frequent other events
EventPerampanel 12 mg
DizzinessNervous system disorders15/54
FatigueGeneral disorders9/54
SomnolenceNervous system disorders8/54
VomitingGastrointestinal disorders6/54
NasopharyngitisInfections and infestations5/54
HeadacheNervous system disorders5/54
IrritabilityPsychiatric disorders5/54
NauseaGastrointestinal disorders4/54
Ear infectionInfections and infestations4/54
Upper respiratory tract infectionInfections and infestations3/54

Baseline characteristics

The Safety Analysis Set included participants who received at least 1 dose of study drug and had at least 1 post-dose safety assessment.

Age, Continuous
Age, Continuous(years)Perampanel 12 mg
Mean38.5 ± 17.32
Sex: Female, Male
Sex: Female, Male(Participants)Perampanel 12 mg
Female27
Male27
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Perampanel 12 mg
Hispanic or Latino7
Not Hispanic or Latino47
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Perampanel 12 mg
American Indian or Alaska Native0
Asian1
Native Hawaiian or Other Pacific Islander0
Black or African American9
White42
More than one race0
Unknown or Not Reported2
07

Study locations

24 sites
  • The Board of Trustees of the University of Alabama for the University of Alabama at Birmingham
    Birmingham, Alabama 35294, United States
  • Barrow Neurological Institute
    Phoenix, Arizona 85013, United States
  • Arkansas Epilepsy Program
    Little Rock, Arkansas 72205, United States
  • UCSD Epilepsy Center
    La Jolla, California 92393, United States
  • Stanford Medical Center
    Palo Alto, California 94304, United States
  • UC Davis Medical Center
    Sacramento, California 95817, United States
  • Baptist Health, Nemours Children's Specialty Care
    Jacksonville, Florida 32207, United States
  • RUSH University Medical Center
    Chicago, Illinois 60612, United States
  • University of Kentucky
    Lexington, Kentucky 40536, United States
  • Johns Hopkins Medicine
    Baltimore, Maryland 21287, United States
  • Mid-Atlantic Epilepsy and Sleep Center
    Bethesda, Maryland 20817, United States
  • Tufts Medical Center
    Boston, Massachusetts 02111, United States
  • The Regents of The University of Michigan
    Ann Arbor, Michigan 48109, United States
  • Michigan State University
    East Lansing, Michigan 48824, United States
  • Minneapolis Clinic of Neurology
    Golden Valley, Minnesota 55442, United States
  • JFK Medical Center
    Edison, New Jersey 08820, United States
  • Northeast Regional Epilepsy Group
    Hackensack, New Jersey 07601, United States
  • UNM Health Providers
    Albuquerque, New Mexico 87106, United States
  • Mount Sinai Medical Center
    New York, New York 10016, United States
  • Duke Neurology
    Durham, North Carolina 27710, United States
  • University Hospitals Cleveland Medical Center
    Cleveland, Ohio 44106, United States
  • Cleveland Clinic
    Cleveland, Ohio 44195, United States
  • UT Southwestern Medical Center
    Dallas, Texas 75390, United States
  • Children's Hospital of San Antonio
    San Antonio, Texas 78207, United States
08

References and documents

Study documents

  • Study protocol · Apr 12, 2019
  • Statistical analysis plan · May 17, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

09

Registry details

Key details

Study ID
NCT03288129
Lead sponsor
Eisai Inc.
Responsible party
Sponsor
First posted
Sep 19, 2017
Start date
Aug 23, 2017
Primary completion
Apr 27, 2021
Completion
Apr 27, 2021
Results posted
May 16, 2022
Last update
May 16, 2022

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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