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

NCT ID: NCT03288129

Last Updated: 2022-05-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-23
• Study Completion Date: 2021-04-27

Brief 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).

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Perampanel

Intervention Type: DRUG

film-coated tablets

Interventions

Perampanel

film-coated tablets

Intervention Type: DRUG

Other Intervention Names

Fycompa; E2007

Eligibility Criteria

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

• 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

• Minimum Eligible Age: 4 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eisai Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The Board of Trustees of the University of Alabama for the University of Alabama at Birmingham

Birmingham, Alabama, United States

Barrow Neurological Institute

Phoenix, Arizona, United States

Arkansas Epilepsy Program

Little Rock, Arkansas, United States

UCSD Epilepsy Center

La Jolla, California, United States

Stanford Medical Center

Palo Alto, California, United States

UC Davis Medical Center

Sacramento, California, United States

Baptist Health, Nemours Children's Specialty Care

Jacksonville, Florida, United States

RUSH University Medical Center

Chicago, Illinois, United States

University of Kentucky

Lexington, Kentucky, United States

Johns Hopkins Medicine

Baltimore, Maryland, United States

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, United States

Tufts Medical Center

Boston, Massachusetts, United States

The Regents of The University of Michigan

Ann Arbor, Michigan, United States

Michigan State University

East Lansing, Michigan, United States

Minneapolis Clinic of Neurology

Golden Valley, Minnesota, United States

JFK Medical Center

Edison, New Jersey, United States

Northeast Regional Epilepsy Group

Hackensack, New Jersey, United States

UNM Health Providers

Albuquerque, New Mexico, United States

Mount Sinai Medical Center

New York, New York, United States

Duke Neurology

Durham, North Carolina, United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

UT Southwestern Medical Center

Dallas, Texas, United States

Children's Hospital of San Antonio

San Antonio, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-001180-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

E2007-G000-410

Identifier Type: -

Identifier Source: org_study_id