Study of Perampanel as Adjunctive Treatment for Inadequately Controlled Seizures Associated With Lennox-Gastaut Syndrome

NCT ID: NCT02834793

Last Updated: 2022-03-09

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

101 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-12-13

Study Completion Date

2021-07-19

Brief Summary

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This study is being conducted to demonstrate that perampanel given as adjunctive anti-epileptic treatment is superior to placebo in reducing the number of drop seizures in participants with inadequately controlled seizures associated with Lennox-Gastaut Syndrome (LGS).

Detailed Description

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This is a multicenter, double-blind, randomized, placebo-controlled, parallel-group study of perampanel as adjunctive therapy in participants with inadequately controlled seizures associated with LGS. The study will consist of 3 phases: Prerandomization (4 to 8 weeks), Randomization (18 weeks), and an Extension A (52 weeks). An additional Extension B with open-label treatment will be available for optional participation to participants who reside in Japan and in countries where an expanded access program (EAP) cannot be implemented or has not yet been implemented.

Conditions

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Lennox-Gastaut Syndrome (LGS)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Matching placebo

During the Randomization Phase, participants will receive matching placebo for up to 18 weeks.

During the Extension A, participants who received placebo during the Randomization Phase will begin treatment with perampanel in a blinded manner in double-blind Conversion Period, starting at 2 mg/day and then up-titrated to a maximum target dose of 8 mg/day according to individual tolerability and efficacy. After the Conversion Period, participants can be titrated up to 12 mg/day (at 2-week intervals) per the investigator's discretion.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Participants will receive matching placebo in Randomization phase.

Perampanel

Intervention Type DRUG

Participants will receive perampanel in Randomization phase, open-label Extension A, and open-label Extension B.

Perampanel up to 8 mg/day

During the Randomization Phase, participants will receive perampanel at a starting dose of 2 milligrams per day (mg/day). Thereafter, the dose will be increased to a maximum target dose of 8 mg/day according to individual tolerability and efficacy for up to 18 weeks. Participants who enter into Extension A will continue to receive perampanel at the dose last received during randomization phase. Participants can be titrated up to 12 mg/day (at 2-week intervals) per the investigator's discretion.

Participants who continue in Extension B will continue to receive perampanel at the dose last received at the end of Extension A.

Group Type EXPERIMENTAL

Perampanel

Intervention Type DRUG

Participants will receive perampanel in Randomization phase, open-label Extension A, and open-label Extension B.

Interventions

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Placebo

Participants will receive matching placebo in Randomization phase.

Intervention Type DRUG

Perampanel

Participants will receive perampanel in Randomization phase, open-label Extension A, and open-label Extension B.

Intervention Type DRUG

Other Intervention Names

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E2007

Eligibility Criteria

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Inclusion Criteria

* Participants must have a diagnosis of LGS as evidenced by:

1. more than one type of generalized seizure, including drop seizures (atonic, tonic, or myoclonic) for at least 6 months before Visit 1;
2. an electroencephalogram (EEG) reporting diagnostic criteria for LGS at some point in their history (abnormal background activity accompanied by slow, spike, and wave pattern \<2.5 hertz \[Hz\]).
* Participants must be at least 2 years old at the time of consent/assent
* Participants must have been \<11 years old at the onset of LGS
* Participants must have experienced an average of at least 2 drop seizures per week in the 4-week Baseline Period preceding randomization
* Participants must have been receiving 1 to 4 concomitant antiepileptic drugs (AEDs) at a stable dose for at least 30 days before Visit 1 (vagal nerve stimulation (VNS) and ketogenic diet do not count as AEDs). Use of cannabidiol (CBD) products is allowed and is counted as one of the 4 maximum allowed concomitant AEDs. CBD dose and product must have remained stable for at least 30 days before Visit 1 and is to remain the same throughout the course of the Core Study
* In the investigator's opinion, parents or caregivers must be able to keep accurate seizure diaries
* Body weight at least 8 kilogram (kg)

Exclusion Criteria

* Presence of progressive neurological disease
* Presence of drop seizure clusters where individual seizures cannot be reliably counted (seizure clusters are defined as ≥2 drop seizures with \<5 minutes between any 2 consecutive seizures)
* Prior treatment with perampanel with discontinuation due to safety issues (related to perampanel)
* Prior treatment with perampanel within 30 days before Visit 1
* 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
* Scheduled for epilepsy-related surgery or any other form of surgery during the projected course of the study
* Ketogenic diet and VNS, unless stable and ongoing for at least 30 days before Visit 1
* Treatment with an investigational drug or device within 30 days before Visit 1
* Status epilepticus within 12 weeks of Visit 1
* If felbamate is used as a concomitant AED, participants must be on felbamate for at least 1 year, with a stable dose for 60 days before Visit 1. They must not have a history of white blood cell (WBC) count below ≤2500/microliters (μL), platelets \<100,000/μL, liver function tests (LFTs) \>3 times the upper limit of normal (ULN), or other indication of hepatic or bone marrow dysfunction while receiving felbamate
* Concomitant use of vigabatrin: participants who took vigabatrin in the past must be discontinued for at least 5 months before Visit 1, and must have documentation showing no evidence of a vigabatrin-associated clinically significant abnormality in an automated visual perimetry test
* Have had multiple drug allergies or a severe drug reaction to an AED(s), including dermatological (eg, Stevens-Johnson syndrome), hematological, or organ toxicity reactions
* Evidence of significant active hepatic disease. Stable elevations of liver enzymes, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) due to concomitant medication(s) will be allowed if they are \< 3 times the ULN
* Adrenocorticotropic hormone within the 6 months before Visit 1
* Had history of anoxic episodes requiring resuscitation within 6 months before Visit 1
* Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta human chorionic gonadotropin \[ß-hCG\] with a minimum sensitivity of 25 International Units per Liter (IU/L) or equivalent units of ß-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: a. had unprotected sexual intercourse within 30 days before study entry and who do not agree to use a highly effective method of contraception (eg, total abstinence, an intrauterine device, a double-barrier method \[such as condom plus diaphragm with spermicide\], a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period or for 28 days after study drug discontinuation. Females using hormonal contraceptives containing levogesterol must be on another form of contraception as well. b. Are currently abstinent, and do not agree to use a double-barrier method (as described above) or refrain from sexual activity during the study period or for 28 days after study drug discontinuation. c. Are using hormonal contraceptives but are not on a stable dose of the same hormonal contraceptive product for at least 4 weeks before dosing and who do not agree to use the same contraceptive during the study or for 28 days after study drug discontinuation. (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 \[i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing\])
* Had intermittent use of benzodiazepine of more than 4 single administrations in the month before Visit 1
* A prolonged QT/QTc interval (QTc \>450 milliseconds \[ms\]) as demonstrated by a repeated electrocardiogram (ECG)
* Hypersensitivity to the study drug or any of the excipients
* Any history of a medical condition or a concomitant medical condition that in the opinion of the investigator(s) would compromise the participant's ability to safely complete the study
* Known to be human immunodeficiency virus (HIV) positive
* Active viral hepatitis (B or C) as demonstrated by positive serology at Screening
* Psychotic disorder(s) or unstable recurrent affective disorder(s) evident by use of antipsychotics or prior suicide attempt(s) within approximately the last 2 years
* History of drug or alcohol dependency or abuse within approximately the last 2 years; use of illegal recreational drugs
* Concomitant use of medications known to be inducers of cytochrome P450 (CYP3A) including, but not limited to: rifampin, troglitazone, St. John's Wort, efavirenz, nevirapine, glucocorticoids (other than topical usage), modafinil, pioglitazone, and rifabutin
* Use of AEDs not recommended by Epilepsy Treatment Guidelines for use in LGS including, but not limited to carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine, and vigabatrin
* Any suicidal ideation with intent with or without a plan within 6 months before Visit 2 (that is, answering "Yes" to questions 4 or 5 on the Suicidal Ideation section of the Columbia Suicide Severity Rating Scale (C -SSRS) in participants aged 8 and above.
* Participants with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
Minimum Eligible Age

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eisai Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Stanford University

Palo Alto, California, United States

Site Status

Northwest Florida Clinical Research Group, LLC

Gulf Breeze, Florida, United States

Site Status

University of Florida Jacksonville

Jacksonville, Florida, United States

Site Status

Pediatric Neurologists of Palm Beach

Loxahatchee Groves, Florida, United States

Site Status

Axcess Medical Research

Loxahatchee Groves, Florida, United States

Site Status

Nicklaus Children's Hospital

Miami, Florida, United States

Site Status

Pediatric Neurology PA

Orlando, Florida, United States

Site Status

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Site Status

Consultants In Epilepsy and Neurology PLLC

Boise, Idaho, United States

Site Status

Carle Foundation Hospital

Urbana, Illinois, United States

Site Status

Midatlantic Epilepsy and Sleep Center

Bethesda, Maryland, United States

Site Status

Children's Hospital of Michigan

Detroit, Michigan, United States

Site Status

Wayne State University

Detroit, Michigan, United States

Site Status

Mercy Health Saint Mary's Campus

Grand Rapids, Michigan, United States

Site Status

Minnesota Epilepsy Group PA

Saint Paul, Minnesota, United States

Site Status

Children's Mercy Hospital

Kansas City, Missouri, United States

Site Status

Children's Hospital at Saint Peter's University Hospital

New Brunswick, New Jersey, United States

Site Status

Cincinnati Children's Hospital Medical Center - PIN

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status

The University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Austin Epilepsy Care Center

Austin, Texas, United States

Site Status

Road Runner Research Ltd

San Antonio, Texas, United States

Site Status

Baylor Scott and White Research Institute

Temple, Texas, United States

Site Status

Clinical Neurosciences Center

Salt Lake City, Utah, United States

Site Status

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

MultiCare Institute for Research and Innovation

Tacoma, Washington, United States

Site Status

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Site Status

Columbia Saint Mary's

Milwaukee, Wisconsin, United States

Site Status

Medical College of Wisconsin

Wauwatosa, Wisconsin, United States

Site Status

Queensland Children's Hospital

South Brisbane, Queensland, Australia

Site Status

Austin Health

Heidelberg, Victoria, Australia

Site Status

Royal Brisbane & Women's Hospital

Brisbane, , Australia

Site Status

Royal Melbourne Hospital

Melbourne, , Australia

Site Status

St Vincent's Hospital Melbourne

Melbourne, , Australia

Site Status

The Alfred Hospital

Melbourne, , Australia

Site Status

Cliniques Universitaires Saint-Luc

Brussels, Brussels Capital, Belgium

Site Status

Hôpital Universitaire des Enfants Reine Fabiola

La Louvière, Hainaut, Belgium

Site Status

Hôpital Erasme

Brussels, , Belgium

Site Status

UZ Brussel

Jette, , Belgium

Site Status

Centre Neurologique William Lennox

Ottignies-Louvain-la-Neuve, , Belgium

Site Status

Fakultni nemocnice Ostrava

Poruba, , Czechia

Site Status

Thomayerova nemocnice

Prague, , Czechia

Site Status

Synexus Affiliate - Panchshil Hospital

Ahmedabad, Gujarat, India

Site Status

Synexus Affiliate - Nirmal Hospitals Pvt. Ltd

Surat, Gujarat, India

Site Status

Synexus Affiliate - Mallikatta Neuro Center

Mangalore, Karnataka, India

Site Status

Synexus Affiliate - Amrita Institute of Medical Sciences and Research Centre

Kochi, Kerala, India

Site Status

Synexus Affiliate - Jaslok Hospital and Research Centre

Mumbai, Maharashtra, India

Site Status

Synexus Affiliate - Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute

Mumbai, Maharashtra, India

Site Status

Synexus Affiliate - Bharati Hospital

Pune, Maharashtra, India

Site Status

Nizams Institute of Medical Sciences

Hyderabad, , India

Site Status

Synexus Affiliate - Sir Ganga Ram Hospital

New Delhi, , India

Site Status

Eisai Trial Site #1

Fukuoka, , Japan

Site Status

Eisai Trial Site #3

Fukuoka, , Japan

Site Status

Eisai Trial Site #7

Hakodate, , Japan

Site Status

EIsai Trial Site #9

Kagoshima, , Japan

Site Status

Eisai Trial Site #4

Niigata, , Japan

Site Status

EIsai Trial Site #8

Osaka, , Japan

Site Status

Eisai Trial Site #6

Sapporo, , Japan

Site Status

Eisai Trial Site #2

Shizuoka, , Japan

Site Status

Kyungpook National University Chilgok hospital

Daegu, , South Korea

Site Status

Severance Hospital Yonsei University Health System - PPDS

Seoul, , South Korea

Site Status

Samsung Medical Center - PPDS

Seoul, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Countries

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United States Australia Belgium Czechia India Japan South Korea

References

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Brigo F, Jones K, Eltze C, Matricardi S. Anti-seizure medications for Lennox-Gastaut syndrome. Cochrane Database Syst Rev. 2021 Apr 7;4(4):CD003277. doi: 10.1002/14651858.CD003277.pub4.

Reference Type DERIVED
PMID: 33825230 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2014-002321-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

E2007-G000-338

Identifier Type: -

Identifier Source: org_study_id

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