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

NCT02834793 | Terminated Phase 3 Results FDA Drug

• 2 other identifiers: E2007-G000-3382014-002321-35
• Study Type: interventional
• Target: 101
• Locations: 7 countries
• Sites: 65

Brief Summary

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).

Conditions

Lennox-Gastaut Syndrome (LGS)

Keywords

Lennox-Gastaut Syndrome (LGS); Inadequately controlled seizures

Outcome Measures

Primary Outcomes (1)

• Core Study Phase: Median Percent Change in Drop Seizure Frequency Per 28 Days During Double-blind Treatment Relative to the Prerandomization Phase (Baseline)

  Drop seizure was defined as a drop attack or spell involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the participant's head hitting a surface or that could have led to a fall or injury, depending on the participant's position at the time of the attack or spell. Seizure frequency was based on the number of drop seizures per 28 days, calculated as the number of drop seizures over the entire time interval divided by the number of days in the interval and multiplied by 28.

  Baseline up to 18 weeks

Secondary Outcomes (12)

• Core Study Phase: Median Percent Change in Total Seizure Frequency Per 28 Days During Double-blind Treatment Relative to the Prerandomization Phase (Baseline)

  Baseline up to 18 weeks

• Core Study Phase: Percentage of Participants With 50% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Drop Seizures

  Baseline up to 18 weeks

• Core Study Phase: Percentage of Participants With 50% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Total Seizures

  Baseline up to 18 weeks

• Core Study Phase: Median Percent Change in Non-drop Seizure Frequency Per 28 Days During Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline)

  Baseline up to 18 weeks

• Core Study Phase: Percentage of Participants With 75% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Drop Seizures, Non-drop Seizures and Total Seizures

  Baseline up to 18 weeks

Study Arms (2)

Perampanel up to 8 mg/day

EXPERIMENTAL

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.

Drug: Perampanel

Matching placebo

PLACEBO COMPARATOR

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.

Drug: Placebo; Drug: Perampanel

Interventions

Placebo DRUG

Participants will receive matching placebo in Randomization phase.

Matching placebo

Perampanel DRUG

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

Also known as: E2007

Matching placebo; Perampanel up to 8 mg/day

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have a diagnosis of LGS as evidenced by:
• more than one type of generalized seizure, including drop seizures (atonic, tonic, or myoclonic) for at least 6 months before Visit 1;
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (65)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72202-3500, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Northwest Florida Clinical Research Group, LLC

Gulf Breeze, Florida, 32561, United States

Location

University of Florida Jacksonville

Jacksonville, Florida, 32209, United States

Location

Pediatric Neurologists of Palm Beach

Loxahatchee Groves, Florida, 33470, United States

Location

Axcess Medical Research

Loxahatchee Groves, Florida, United States

Location

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

Location

Pediatric Neurology PA

Orlando, Florida, 32819, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30342, United States

Location

Consultants In Epilepsy and Neurology PLLC

Boise, Idaho, 83702, United States

Location

Carle Foundation Hospital

Urbana, Illinois, 61801, United States

Location

Midatlantic Epilepsy and Sleep Center

Bethesda, Maryland, 20817, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

Mercy Health Saint Mary's Campus

Grand Rapids, Michigan, 49301, United States

Location

Minnesota Epilepsy Group PA

Saint Paul, Minnesota, 55102, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Children's Hospital at Saint Peter's University Hospital

New Brunswick, New Jersey, 08901, United States

Location

Cincinnati Children's Hospital Medical Center - PIN

Cincinnati, Ohio, 45229, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

The University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Austin Epilepsy Care Center

Austin, Texas, 78758, United States

Location

Road Runner Research Ltd

San Antonio, Texas, 78249, United States

Location

Baylor Scott and White Research Institute

Temple, Texas, 76508, United States

Location

Clinical Neurosciences Center

Salt Lake City, Utah, 84132, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

MultiCare Institute for Research and Innovation

Tacoma, Washington, 98405, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Columbia Saint Mary's

Milwaukee, Wisconsin, 53211, United States

Location

Medical College of Wisconsin

Wauwatosa, Wisconsin, 53226, United States

Location

Queensland Children's Hospital

South Brisbane, Queensland, 4101, Australia

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

Royal Brisbane & Women's Hospital

Brisbane, Australia

Location

Royal Melbourne Hospital

Melbourne, Australia

Location

St Vincent's Hospital Melbourne

Melbourne, Australia

Location

The Alfred Hospital

Melbourne, Australia

Location

Cliniques Universitaires Saint-Luc

Brussels, Brussels Capital, 1200, Belgium

Location

Hôpital Universitaire des Enfants Reine Fabiola

La Louvière, Hainaut, Belgium

Location

Hôpital Erasme

Brussels, Belgium

Location

UZ Brussel

Jette, Belgium

Location

Centre Neurologique William Lennox

Ottignies-Louvain-la-Neuve, Belgium

Location

Fakultni nemocnice Ostrava

Poruba, Czechia

Location

Thomayerova nemocnice

Prague, Czechia

Location

Synexus Affiliate - Panchshil Hospital

Ahmedabad, Gujarat, India

Location

Synexus Affiliate - Nirmal Hospitals Pvt. Ltd

Surat, Gujarat, India

Location

Synexus Affiliate - Mallikatta Neuro Center

Mangalore, Karnataka, India

Location

Synexus Affiliate - Amrita Institute of Medical Sciences and Research Centre

Kochi, Kerala, India

Location

Synexus Affiliate - Jaslok Hospital and Research Centre

Mumbai, Maharashtra, India

Location

Synexus Affiliate - Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute

Mumbai, Maharashtra, India

Location

Synexus Affiliate - Bharati Hospital

Pune, Maharashtra, India

Location

Nizams Institute of Medical Sciences

Hyderabad, 500082, India

Location

Synexus Affiliate - Sir Ganga Ram Hospital

New Delhi, India

Location

Eisai Trial Site #1

Fukuoka, Japan

Location

Eisai Trial Site #3

Fukuoka, Japan

Location

Eisai Trial Site #7

Hakodate, Japan

Location

EIsai Trial Site #9

Kagoshima, Japan

Location

Eisai Trial Site #4

Niigata, Japan

Location

EIsai Trial Site #8

Osaka, 534-0021, Japan

Location

Eisai Trial Site #6

Sapporo, Japan

Location

Eisai Trial Site #2

Shizuoka, Japan

Location

Kyungpook National University Chilgok hospital

Daegu, South Korea

Location

Severance Hospital Yonsei University Health System - PPDS

Seoul, 03722, South Korea

Location

Samsung Medical Center - PPDS

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Related Publications (1)

• 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.

  PMID: 33825230 DERIVED

MeSH Terms

Conditions

Lennox Gastaut Syndrome

Interventions

perampanel

Condition Hierarchy (Ancestors)

Epileptic Syndromes; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Limitations and Caveats

Study was terminated early by sponsor due to recruitment challenge, further impacted by COVID19, resulting in reduced sample size and variability in treatment response. Population PK analysis and PK/PD modeling planned for this study were not conducted and hence data was not collected and analyzed.

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_medinfo@eisai.com

+1-888-274-2378

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2016
• First Posted: July 15, 2016
• Study Start: December 13, 2016
• Primary Completion: May 26, 2021
• Study Completion: July 19, 2021
• Last Updated: March 9, 2022
• Results First Posted: March 9, 2022

Record last verified: 2021-03

Locations

JP (8); US (31); CZ (2); BE (5); IN (9); AU (6); KR (4)