Evaluating the Efficacy and Safety of E2007 (Perampanel) Given as Adjunctive Therapy in Subjects With Refractory Partial Seizures

NCT ID: NCT00699972

Last Updated: 2020-01-10

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

390 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-04-30

Study Completion Date

2010-10-19

Brief Summary

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The purpose of this study is to evaluate the safety, efficacy and tolerability of perampanel when given as an adjunctive therapy in subjects with refractory partial seizures.

Detailed Description

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Conditions

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Refractory Partial Seizures

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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1

Group Type EXPERIMENTAL

E2007 (perampanel)

Intervention Type DRUG

8 mg perampanel in a 1:1:1 ratio, 125 subjects/arm. All subjects will take a maximum of 6 tablets daily for the duration of the study and will be up-titrated weekly in 2-mg increments to their randomized dose.

2

Group Type EXPERIMENTAL

E2007 (perampanel)

Intervention Type DRUG

12 mg perampanel in a 1:1:1 ratio, 125 subjects/arm. All subjects will take a maximum of 6 tablets daily for the duration of the study and will be up-titrated weekly in 2-mg increments to their randomized dose.

3

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo in a 1:1:1 ratio, 125 subjects/arm. All subjects will take a maximum of 6 tablets daily for the duration of the study.

Interventions

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E2007 (perampanel)

8 mg perampanel in a 1:1:1 ratio, 125 subjects/arm. All subjects will take a maximum of 6 tablets daily for the duration of the study and will be up-titrated weekly in 2-mg increments to their randomized dose.

Intervention Type DRUG

E2007 (perampanel)

12 mg perampanel in a 1:1:1 ratio, 125 subjects/arm. All subjects will take a maximum of 6 tablets daily for the duration of the study and will be up-titrated weekly in 2-mg increments to their randomized dose.

Intervention Type DRUG

Placebo

Placebo in a 1:1:1 ratio, 125 subjects/arm. All subjects will take a maximum of 6 tablets daily for the duration of the study.

Intervention Type DRUG

Other Intervention Names

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Perampanel Perampanel

Eligibility Criteria

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Inclusion Criteria

Each subject must meet all of the following criteria to be enrolled in this study:

1. Provide written informed consent signed by the subject or legal guardian prior to entering the study or undergoing any study procedures (If the written informed consent is provided by the legal guardian because the subject is unable to do so, a written or verbal assent from the subject must also be obtained).
2. Be considered reliable and willing to be available for the study period and able to record seizures and report Adverse Events (AEs) them self or have a caregiver who can record seizures and report AEs for them.
3. Male or female and greater than or equal to 12 years of age (within the course of the study).
4. Females should be either of non-childbearing potential (defined as having undergone surgical sterilization, or postmenopausal \[age 50 and amenorrheic for 12 months\]) or of childbearing potential. Females of childbearing potential must have a negative serum Beta Human Chorionic Gonadotropin (ß-hCG) at Visit 1 and a negative urine pregnancy test prior to randomization at Visit 2. Female subjects of childbearing potential must agree to be abstinent or to use at least 1 medically acceptable method of contraception (eg, a double-barrier method \[eg, condom + spermicide, condom + diaphragm with spermicide\], IUD, or have a vasectomised partner) starting at Visit 1 and throughout the entire study period and for 2 months after the last dose of study drug. Those women using hormonal contraceptives must also be using an additional approved method of contraception (as described previously) starting at Visit 1 and continuing throughout the entire study period and for 2 months after the last dose of study drug. (It is not required for male subjects to use contraceptive measures based on preclinical toxicology data).
5. Have a diagnosis of epilepsy with partial seizures with or without secondarily generalized seizures according to the International League Against Epilepsy's Classification of Epileptic Seizures (1981). Diagnosis should have been established by clinical history and an electroencephalogram (EEG) that is consistent with localization-related epilepsy; normal interictal EEGs will be allowed provided that the subject meets the other diagnosis criterion (ie, clinical history).
6. Have had a computed tomography (CT) or magnetic resonance imaging (MRI) within the last 10 years that ruled out a progressive cause of epilepsy.
7. Have uncontrolled partial seizures despite having been treated with at least 2 different anti-epileptic drugs (AEDs) within approximately the last 2 years.
8. During the 6-week Pre-randomization Phase subjects must have had ≥5 partial seizures per 6-week (with ≥2 partial seizures per each of 3-week period) and with no 25-day seizure-free period in the 6-week period, as documented via a valid seizure diary. Only simple partial seizures with motor signs, complex partial seizures, and complex partial seizures with secondary generalization are counted toward this inclusion.
9. Are currently being treated with stable doses of 1, 2 or a maximum of 3 approved AEDs. Only 1 inducer AED (defined as; carbamazepine, phenytoin, phenobarbital, or primidone only) out of the maximum of 3 AEDs is allowed.
10. Are on a stable dose of the same concomitant AED(s) for 1 month (or no less than 21 days) prior to Visit 1; in the case where a new AED regime has been initiated for a subject, the dose must be stable for 2 months (or no less than 49 days) prior to Visit 1.
11. If on a stable dose (other than intermittent rescue use) of benzodiazepines for epilepsy (or for anxiety or sleep disorders) the prescribed dose must be stable for 1 month (or no less than 21 days) prior to Visit 1. (Note: the use of intermittent rescue benzodiazepines is defined in the exclusion criterion #22 below.) When used in these cases (epilepsy, anxiety or sleep disorders), benzodiazepines will be counted as 1 AED; therefore, only 1 or a maximum of 2 additional approved AEDs will be allowed.
12. A vagal nerve stimulator (VNS) is allowed but it must have been implanted ≥5 months prior to Visit 1. Stimulator parameters can not be changed for 1 month (or no less than 21 days) prior to Visit 1 or thereafter during the study.

Exclusion Criteria

Subjects who meet any of the following criteria will be excluded from the study:

1. Participated in a study involving administration of an investigational compound or device within 1 month (or no less than 21 days) prior to Visit 1, or within approximately 5 half-lives of the previous investigational compound, whichever is longer.
2. Pregnant and/or lactating.
3. Participated in previous perampanel studies.
4. Presence of nonmotor simple partial seizures only.
5. Presence of primary generalized epilepsies or seizures, such as absences and or myoclonic epilepsies.
6. Presence or previous history of Lennox-Gastaut syndrome.
7. A history of status epilepticus within approximately 12 months prior to Visit 1.
8. Seizure clusters where individual seizures cannot be counted.
9. A history of psychogenic seizures.
10. Evidence of clinically significant disease (eg, cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the Investigator(s) could affect the subject's safety or the study conduct.
11. Scheduled and/or confirmed to have epilepsy surgery within 6 months after Visit 1; however those who have previously documented "failed" epilepsy surgery will be allowed.
12. 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 less than 3 times the upper limit of normal (ULN).
13. Evidence of significant active hematological disease; white blood cell (WBC) count \<= 2500/µL (2.50 1E+09/L) or an absolute neutrophil count \<= 1000/µL (1.00 1E+09/L).
14. A clinically significant electrocardiogram (ECG) abnormality, including prolonged QTc defined as \>450 msec.
15. Suffering from psychotic disorder(s) and/or unstable recurrent affective disorder(s) evident by use of antipsychotics or have had a suicide attempt(s) within approximately the last 2 years.
16. Presence of a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors.
17. History of drug or alcohol dependency or abuse within approximately the last 2 years.
18. 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.
19. If felbamate is used as a concomitant AED, subjects must be on felbamate for at least 2 years, with a stable dose for 2 months (or no less than 49 days) prior to Visit 1. They must not have a history of white blood cell (WBC) count below 2500/µL (2.50 1E+09/L), platelets below 100,000, liver function tests (LFTs) above 3 times the upper limit of normal (ULN), or other indication of hepatic or bone marrow dysfunction while receiving felbamate. If subjects received felbamate in the past, it must have been discontinued 2 months (or no less than 49 days) prior to Visit 1.
20. Concomitant use of vigabatrin. Subjects who took vigabatrin in the past must be off vigabatrin for approximately 5 months prior to Visit 1 and must have documentation showing no evidence of a vigabatrin associated clinically significant abnormality in a visual perimetry test.
21. Concomitant use of barbiturates (except for seizure control indication) within 1 month (or no less than 21 days) prior to Visit 1.
22. Use of intermittent rescue benzodiazepines (ie, 1-2 doses over a 24-hr period considered one-time rescue) 2 or more times in a 1-month period prior to Visit 1; or
23. Any condition(s) that will make the subject, in the opinion of the Investigator, unsuitable for the study.
Minimum Eligible Age

12 Years

Maximum Eligible Age

99 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

Principal Investigators

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David Squillacote, M.D.

Role: STUDY_DIRECTOR

Eisai Inc.

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

St. Joseph's Hospital And Medical Center

Phoenix, Arizona, United States

Site Status

Clinical Trials, Inc.

Little Rock, Arkansas, United States

Site Status

Childrens Hospital Los Angeles

Los Angeles, California, United States

Site Status

Bright Minds Institute

San Francisco, California, United States

Site Status

California Pacific Medical Center

San Francisco, California, United States

Site Status

Mile High Research Center

Denver, Colorado, United States

Site Status

Children's Research Institute

Washington D.C., District of Columbia, United States

Site Status

University of Florida Health Sciences, Jacksonville

Jacksonville, Florida, United States

Site Status

Pediatric Neurology and Epilepsy Center

Loxahatchee Groves, Florida, United States

Site Status

Loxahatchee Groves, Florida, United States

Site Status

Pediatric Neurology PA

Orlando, Florida, United States

Site Status

North West Florida Clinical Research Group

Pensacola, Florida, United States

Site Status

Child Neurology Center Of Nw Florida

Pensacola, Florida, United States

Site Status

Lovelace Scientific Resources

Sarasota, Florida, United States

Site Status

Ronald Aung-Din, MD, PC

Sarasota, Florida, United States

Site Status

Tallahassee Neurological Clinic

Tallahassee, Florida, United States

Site Status

Pediatric Epilepsy and Neurology Specialists

Tampa, Florida, United States

Site Status

PANDA

Atlanta, Georgia, United States

Site Status

Children's Healthcare of Atlanta at Scottish Rite

Atlanta, Georgia, United States

Site Status

Georgia Neurology and Sleep Medicine Associates

Suwanee, Georgia, United States

Site Status

Josephson Wallack Munshower Neurology

Indianapolis, Indiana, United States

Site Status

McFarland Clinic, PC

Ames, Iowa, United States

Site Status

Via Christi Comprehensive Epilepsy Center

Wichita, Kansas, United States

Site Status

Wichita, Kansas, United States

Site Status

University of Kentucky Research Foundation

Lexington, Kentucky, United States

Site Status

Kentucky Neuroscience Research

Louisville, Kentucky, United States

Site Status

Leonard J. Chabert Medical Center

Houma, Louisiana, United States

Site Status

Louisiana State University Health Sciences Center

Shreveport, Louisiana, United States

Site Status

Neurology/Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, United States

Site Status

Boston University Medical Center

Boston, Massachusetts, United States

Site Status

Michigan Neurology Associates, P.C.

Clinton Township, Michigan, United States

Site Status

Washington University

St Louis, Missouri, United States

Site Status

Albany Medical College

Albany, New York, United States

Site Status

Five Towns Neurology, PC

Cedarhurst, New York, United States

Site Status

Long Island Jewish Medical Center

New Hyde Park, New York, United States

Site Status

Univeristy of Rochester Strong Epilepsy Center

Rochester, New York, United States

Site Status

Asheville Neurology Specialists, PA

Asheville, North Carolina, United States

Site Status

Children's Hospital Medical Center Of Akron D/B/A Akron Children's Hospital

Akron, Ohio, United States

Site Status

University Neurology, Inc.

Cincinnati, Ohio, United States

Site Status

The Ohio State University Medical Center

Columbus, Ohio, United States

Site Status

University Of Toledo Medical Center

Toledo, Ohio, United States

Site Status

Neurological Associates of Tulsa, Inc.

Tulsa, Oklahoma, United States

Site Status

Providence St. Vincent's Epilepsy Center

Portland, Oregon, United States

Site Status

Blair Medical Assiciates, Inc.

Altoona, Pennsylvania, United States

Site Status

Children's Hospital Of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

UT Le Bonheur Pediatric Specialists

Memphis, Tennessee, United States

Site Status

Dallas Pediatric Neurology Associates

Dallas, Texas, United States

Site Status

Neurological Clinic of Texas, P.A.

Dallas, Texas, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

Texas Tech University Health Sciences Center

El Paso, Texas, United States

Site Status

Texas Children's Hospital

Houston, Texas, United States

Site Status

Virginia Commonwealth University Medical Center

Richmond, Virginia, United States

Site Status

Harborview Medical Center

Seattle, Washington, United States

Site Status

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Regional Epilepsy Center

Milwaukee, Wisconsin, United States

Site Status

Sanatorio Allende

Córdoba, Córdoba Province, Argentina

Site Status

Hospital San Roque

Córdoba, Córdoba- Provincia de Córdoba, Argentina

Site Status

Hospital Santa Clara de Asis

Salta, Salta Province, Argentina

Site Status

FLENI (Fundación para la Lucha Contra Las Enfermedades Neurológicas de La Infancia)

Capital Federal- Provincia de Buenos Aires, , Argentina

Site Status

Hospital Británico

Capital Federal- Provincia de Buenos Aires, , Argentina

Site Status

Hospital de Niños Ricardo Gutiérrez

Capital Federal- Provincia de Buenos Aires, , Argentina

Site Status

Hospital General de Agudos José María Ramos Mejia

Capital Federal- Provincia de Buenos Aires, , Argentina

Site Status

Hospital General de Agudos Teodoro Álvarez

Capital Federal- Provincia de Buenos Aires, , Argentina

Site Status

Hospital Italiano de Buenos Aires

Capital Federal- Provincia de Buenos Aires, , Argentina

Site Status

Policlínica Bancaria 9 de Julio

Capital Federal- Provincia de Buenos Aires, , Argentina

Site Status

Centro de Estudio y Tratamiento de la Epilepsia y Sueño- CETES S.A.

Córdoba, , Argentina

Site Status

Sanatorio Parque

Rosario, , Argentina

Site Status

Faculdade de Ciências Médicas - UNICAMP

Campinas, , Brazil

Site Status

Hospital de Clinicas da UFPR

Curitiba, , Brazil

Site Status

Santa Casa de Porto Alegre

Porto Alegre, , Brazil

Site Status

HC Ribeirão Preto

Ribeirão Preto, , Brazil

Site Status

Hospital Pedro Ernesto - UERJ

Rio de Janeiro, , Brazil

Site Status

Hospital Universitário Professor Edgar Santos

Salvador, , Brazil

Site Status

Faculdade de Medicinade São José do Rio preto

São José do Rio Preto, , Brazil

Site Status

HC-FMUSP

São Paulo, , Brazil

Site Status

Hospital Brigadeiro

São Paulo, , Brazil

Site Status

Hospital Santa Marcelina

São Paulo, , Brazil

Site Status

UNIFESP

São Paulo, , Brazil

Site Status

Foothills Medical Center

Calgary, Alberta, Canada

Site Status

London Health Sciences Center

London, Ontario, Canada

Site Status

Youthdale Treatment Centers

Toronto, Ontario, Canada

Site Status

Neuro Rive-Sud

Greenfield Park, Quebec, Canada

Site Status

CHU Sainte-Justine

Montreal, Quebec, Canada

Site Status

Hospital Barros Luco Trudeau

Santiago, , Chile

Site Status

Hospital Base Valdivia Servicio de Neurología

Santiago, , Chile

Site Status

Hospital Dr. Sótero del Río

Santiago, , Chile

Site Status

Neuropsicología Ltda.

Santiago, , Chile

Site Status

MIRC

Monterrey, Nuevo Leon CP, Mexico

Site Status

Instituto Biomedico de Investigacion AC

Aguascalientes, , Mexico

Site Status

Sarug Reyes

Aguascalientes, , Mexico

Site Status

Medica Sur SIF-BIOTEC

Mexico City, , Mexico

Site Status

Hospital Central "Dr. Ignacio Morones Prieto"

San Luis Potosí City, , Mexico

Site Status

Countries

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United States Argentina Brazil Canada Chile Mexico

References

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French JA, Krauss GL, Biton V, Squillacote D, Yang H, Laurenza A, Kumar D, Rogawski MA. Adjunctive perampanel for refractory partial-onset seizures: randomized phase III study 304. Neurology. 2012 Aug 7;79(6):589-96. doi: 10.1212/WNL.0b013e3182635735. Epub 2012 Jul 25.

Reference Type RESULT
PMID: 22843280 (View on PubMed)

Bresnahan R, Hill RA, Wang J. Perampanel add-on for drug-resistant focal epilepsy. Cochrane Database Syst Rev. 2023 Apr 14;4(4):CD010961. doi: 10.1002/14651858.CD010961.pub2.

Reference Type DERIVED
PMID: 37059702 (View on PubMed)

Maguire M. Response to "Perampanel and pregnancy: Could experience be a gloomy lantern that does not even illuminate its bearer?". Epilepsy Behav. 2022 Apr;129:108654. doi: 10.1016/j.yebeh.2022.108654. Epub 2022 Mar 16. No abstract available.

Reference Type DERIVED
PMID: 35305920 (View on PubMed)

French JA, Gil-Nagel A, Malerba S, Kramer L, Kumar D, Bagiella E. Time to prerandomization monthly seizure count in perampanel trials: A novel epilepsy endpoint. Neurology. 2015 May 19;84(20):2014-20. doi: 10.1212/WNL.0000000000001585. Epub 2015 Apr 15.

Reference Type DERIVED
PMID: 25878175 (View on PubMed)

Rosenfeld W, Conry J, Lagae L, Rozentals G, Yang H, Fain R, Williams B, Kumar D, Zhu J, Laurenza A. Efficacy and safety of perampanel in adolescent patients with drug-resistant partial seizures in three double-blind, placebo-controlled, phase III randomized clinical studies and a combined extension study. Eur J Paediatr Neurol. 2015 Jul;19(4):435-45. doi: 10.1016/j.ejpn.2015.02.008. Epub 2015 Mar 5.

Reference Type DERIVED
PMID: 25823975 (View on PubMed)

Steinhoff BJ, Ben-Menachem E, Ryvlin P, Shorvon S, Kramer L, Satlin A, Squillacote D, Yang H, Zhu J, Laurenza A. Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures: a pooled analysis of three phase III studies. Epilepsia. 2013 Aug;54(8):1481-9. doi: 10.1111/epi.12212. Epub 2013 May 10.

Reference Type DERIVED
PMID: 23663001 (View on PubMed)

Other Identifiers

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E2007-G000-304

Identifier Type: -

Identifier Source: org_study_id

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