To Evaluate The Efficacy and Safety of E2007 (Perampanel) Given as Adjunctive Therapy in Subjects With Refractory Partial Seizures

NCT00699582 | Completed Phase 3 Results

• 2 other identifiers: E2007-G000-3052007-006168-31
• Study Type: interventional
• Target: 389
• Locations: 14 countries
• Sites: 92

Brief Summary

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

Conditions

Refractory Partial Seizures

Keywords

E2007 (perampanel); refractory partial seizures; adjunctive therapy; seizure frequency; reduction in seizure frequency; partial onset seizures; safety; concomitant AED(s)

Outcome Measures

Primary Outcomes (1)

• Percent Change in the 28-day Seizure Frequency From Baseline to the End of the Double-blind Phase (Titration and Maintenance Phases)

  Seizure frequency per 28 days was derived from the information recorded in the subject diaries.

  Baseline (Pre-randomization) through Week 19

Secondary Outcomes (2)

• Responder Rate

  Baseline (Pre-randomization) through Week 19

• Percent Change in the 28-day Complex Partial Plus Secondarily Generalized Seizure Frequency From Baseline to the End of the Double-blind Phase (Titration and Maintenance Phases)

  Baseline (Pre-randomization) through Week 19

Study Arms (3)

1

EXPERIMENTAL

Drug: E2007 (perampanel)

2

EXPERIMENTAL

Drug: E2007 (perampanel)

3

PLACEBO COMPARATOR

Drug: Placebo

Interventions

E2007 (perampanel) 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.

Also known as: perampanel

1

Placebo 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.

3

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Each subject must meet all of the following criteria to be enrolled in this study:
• 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).
• 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.
• Male or female and greater than or equal to 12 years of age (within the course of the study), or greater than or equal to 18 years of age (depending on location) at the time of signing the informed consent.
• 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).
• 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).
• Have had a computed tomography (CT) or magnetic resonance imaging (MRI) within the last 10 years that ruled out a progressive cause of epilepsy.
• Have uncontrolled partial seizures despite having been treated with at least 2 different anti-epileptic drugs (AEDs) within approximately the last 2 years.
• 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.
• 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.
• 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.

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from the study:
• 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.
• Pregnant and/or lactating.
• Participated in previous perampanel studies.
• Presence of nonmotor simple partial seizures only.
• Presence of primary generalized epilepsies or seizures, such as absences and or myoclonic epilepsies.
• Presence or previous history of Lennox-Gastaut syndrome.
• A history of status epilepticus within approximately 12 months prior to Visit 1.
• Seizure clusters where individual seizures cannot be counted.
• A history of psychogenic seizures.
• 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.
• 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.
• 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).
• 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).
• A clinically significant ECG abnormality, including prolonged QTc defined as \>450 msec.

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (92)

North Alabama Neuroscience Research Associates

Huntsville, Alabama, 35801, United States

Location

Unknown Facility

Huntsville, Alabama, United States

Location

Xenoscience, Inc.

Phoenix, Arizona, 85004, United States

Location

Unknown Facility

Phoenix, Arizona, United States

Location

University of Arizona

Tucson, Arizona, 85724, United States

Location

Unknown Facility

Tucson, Arizona, United States

Location

Unknown Facility

Fresno, California, United States

Location

Unknown Facility

Sacramento, California, United States

Location

Neurosearch II, Inc.

Ventura, California, 93003, United States

Location

Unknown Facility

Ventura, California, United States

Location

Mile High Research Center

Denver, Colorado, 80218, United States

Location

Neurology Associates of Northern Colorado

Fort Collins, Colorado, 80524, United States

Location

Unknown Facility

Fort Collins, Colorado, United States

Location

Mayo Clinic-Jacksonville

Jacksonville, Florida, 32224, United States

Location

Unknown Facility

Jacksonville, Florida, United States

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Unknown Facility

Boston, Massachusetts, United States

Location

Unknown Facility

Burlington, Massachusetts, United States

Location

Neurological Research Center at Hattiesburg Clinic

Hattiesburg, Mississippi, 39401, United States

Location

Unknown Facility

Hattiesburg, Mississippi, United States

Location

The Comprehensive Care Center for Children And Adults

Chesterfield, Missouri, 63017, United States

Location

Unknown Facility

Chesterfield, Missouri, United States

Location

Saint Luke's Comprehensive Epilepsy Center

Kansas City, Missouri, 64111, United States

Location

Unknown Facility

Kansas City, Missouri, United States

Location

Unknown Facility

Buffalo, New York, United States

Location

NYU Comprehensive Epilepsy Center

New York, New York, 10016, United States

Location

Unknown Facility

New York, New York, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Unknown Facility

Syracuse, New York, United States

Location

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Dallas, Texas, United States

Location

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Salt Lake City, Utah, United States

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Dean Foundation for Health, Research and Education, Inc.

Madison, Wisconsin, 53715, United States

Location

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Madison, Wisconsin, United States

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Graz, 8036, Austria

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Graz, Austria

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Innsbruck, Austria

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Linz, 4021, Austria

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Linz, Austria

Location

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Vienna, 1130, Austria

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Vienna, 1220, Austria

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Vienna, Austria

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Brussels, Belgium

Location

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Ghent, Belgium

Location

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Leuven, Belgium

Location

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Ottignies (lln), Belgium

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Vantaa, Finland

Location

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Angers, France

Location

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Béthune, France

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Bron, France

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Dijon, France

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Montpellier, France

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Rennes, France

Location

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Toulouse, France

Location

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Bad Berka, Germany

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Berlin, Germany

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Bernau, Germany

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Bielefeld, Germany

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Bonn, Germany

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Erlangen, Germany

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Göttingen, Germany

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Mangalore, Karnataka, India

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Nagpur, Maharashtra, India

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Nashik, Maharashtra, India

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New Delhi, India

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Ashkelon, Israel

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Haifa, Israel

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Holon, Israel

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Petah Tikva, Israel

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Ramat Gan, Israel

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Tel Aviv, Israel

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Florence, Italy

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Milan, Italy

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Napoli, Italy

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Haarlem, Netherlands

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Heeze, Netherlands

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Nijmegen, Netherlands

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The Hague, Netherlands

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Zwolle, Netherlands

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Kazan', Russia

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Moscow, Russia

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Nizhny Novgorod, Russia

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Rosebank, Gauteng, South Africa

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Richards Bay, KwaZulu-Natal, South Africa

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Cape Town, Western Cape, South Africa

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Cape Town, South Africa

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Johannesburg, South Africa

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Gothenburg, Sweden

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Linköping, Sweden

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Bristol, United Kingdom

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Liverpool, United Kingdom

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London, United Kingdom

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Middlesbrough, United Kingdom

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Stoke-on-Trent, United Kingdom

Location

Related Publications (6)

• 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.

  PMID: 37059702 DERIVED

• 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.

  PMID: 35305920 DERIVED

• 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.

  PMID: 25878175 DERIVED

• 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.

  PMID: 25823975 DERIVED

• 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.

  PMID: 23663001 DERIVED

• French JA, Krauss GL, Steinhoff BJ, Squillacote D, Yang H, Kumar D, Laurenza A. Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: results of randomized global phase III study 305. Epilepsia. 2013 Jan;54(1):117-25. doi: 10.1111/j.1528-1167.2012.03638.x. Epub 2012 Aug 20.

  PMID: 22905857 DERIVED

MeSH Terms

Conditions

Seizures

Interventions

perampanel

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Eisai Inc.
• Organization: Eisai Call Center

888-422-4743

Study Officials

• David Squillacote, M.D.

  Eisai Inc.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: June 17, 2008
• First Posted: June 18, 2008
• Study Start: May 1, 2008
• Primary Completion: December 1, 2010
• Study Completion: January 1, 2011
• Last Updated: July 11, 2014
• Results First Posted: November 22, 2012

Record last verified: 2012-10

Locations

FR (7); FI (1); NL (5); RU (3); GB (5); IN (4); US (32); AU (8); BE (4); ZA (5); SE (2); IT (3); IL (6); DE (7)