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Refractory Partial SeizuresPhase 3NCT00699582

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

A Phase 3 study testing E2007 (perampanel) in people with Refractory Partial Seizures, run by Eisai Inc. at 92 sites in 14 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Refractory Partial Seizures
What is being tested?
E2007 (perampanel)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
389 participants
Where
92 sitesin 14 countries
Study dates
May 2008to Jan 2011
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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).
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  • 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.
  • During the 6-week Pre-randomization Phase subjects must have had ≥5 partial seizures (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.
  • 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.
  • 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.
  • 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.

Who cannot join

  • 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.
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  • 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.
  • 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.
  • Presence of a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors.
  • History of drug or alcohol dependency or abuse within approximately the last 2 years.
  • 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.
  • 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.
  • 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.
  • Concomitant use of barbiturates (except for seizure control indication) within 1 month (or no less than 21 days) prior to Visit 1.
  • 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
  • Any condition(s) that will make the subject, in the opinion of the Investigator, unsuitable for the study.

Trial locations and contacts

92 sites in 14 countries.

92 sites in 14 countries

United States32 sites

  • Study site

    Boston, Massachusetts

  • Study site

    Buffalo, New York

  • Study site

    Burlington, Massachusetts

  • The Comprehensive Care Center for Children And Adults

    Chesterfield, Missouri, 63017

  • Study site

    Chesterfield, Missouri

  • Study site

    Dallas, Texas

  • Mile High Research Center

    Denver, Colorado, 80218

  • Neurology Associates of Northern Colorado

    Fort Collins, Colorado, 80524

  • Study site

    Fort Collins, Colorado

  • Study site

    Fresno, California

  • Neurological Research Center at Hattiesburg Clinic

    Hattiesburg, Mississippi, 39401

  • Study site

    Hattiesburg, Mississippi

  • North Alabama Neuroscience Research Associates

    Huntsville, Alabama, 35801

  • Study site

    Huntsville, Alabama

  • Mayo Clinic-Jacksonville

    Jacksonville, Florida, 32224

  • Study site

    Jacksonville, Florida

  • Saint Luke's Comprehensive Epilepsy Center

    Kansas City, Missouri, 64111

  • Study site

    Kansas City, Missouri

  • Dean Foundation for Health, Research and Education, Inc.

    Madison, Wisconsin, 53715

  • Study site

    Madison, Wisconsin

  • NYU Comprehensive Epilepsy Center

    New York, New York, 10016

  • Study site

    New York, New York

  • Xenoscience, Inc.

    Phoenix, Arizona, 85004

  • Study site

    Phoenix, Arizona

  • Study site

    Sacramento, California

  • Study site

    Salt Lake City, Utah

  • SUNY Upstate Medical University

    Syracuse, New York, 13210

  • Study site

    Syracuse, New York

  • University of Arizona

    Tucson, Arizona, 85724

  • Study site

    Tucson, Arizona

  • Neurosearch II, Inc.

    Ventura, California, 93003

  • Study site

    Ventura, California

Other trials in United States

Austria8 sites

  • Study site

    Graz, 8036

  • Study site

    Graz

  • Study site

    Innsbruck

  • Study site

    Linz, 4021

  • Study site

    Linz

  • Study site

    Vienna, 1130

  • Study site

    Vienna, 1220

  • Study site

    Vienna

Other trials in Austria

France7 sites

  • Study site

    Angers

  • Study site

    Béthune

  • Study site

    Bron

  • Study site

    Dijon

  • Study site

    Montpellier

  • Study site

    Rennes

  • Study site

    Toulouse

Other trials in France

Germany7 sites

  • Study site

    Bad Berka

  • Study site

    Berlin

  • Study site

    Bernau

  • Study site

    Bielefeld

  • Study site

    Bonn

  • Study site

    Erlangen

  • Study site

    Göttingen

Other trials in Germany

Israel6 sites

  • Study site

    Ashkelon

  • Study site

    Haifa

  • Study site

    Holon

  • Study site

    Petah Tikva

  • Study site

    Ramat Gan

  • Study site

    Tel Aviv

Other trials in Israel

Netherlands5 sites

  • Study site

    Haarlem

  • Study site

    Heeze

  • Study site

    Nijmegen

  • Study site

    The Hague

  • Study site

    Zwolle

Other trials in Netherlands

South Africa5 sites

  • Study site

    Cape Town, Western Cape

  • Study site

    Cape Town

  • Study site

    Johannesburg

  • Study site

    Richards Bay, KwaZulu-Natal

  • Study site

    Rosebank, Gauteng

Other trials in South Africa

United Kingdom5 sites

  • Study site

    Bristol

  • Study site

    Liverpool

  • Study site

    London

  • Study site

    Middlesbrough

  • Study site

    Stoke-on-Trent

Other trials in United Kingdom

Belgium4 sites

  • Study site

    Brussels

  • Study site

    Ghent

  • Study site

    Leuven

  • Study site

    Ottignies (lln)

Other trials in Belgium

India4 sites

  • Study site

    Mangalore, Karnataka

  • Study site

    Nagpur, Maharashtra

  • Study site

    Nashik, Maharashtra

  • Study site

    New Delhi

Other trials in India

Italy3 sites

  • Study site

    Florence

  • Study site

    Milan

  • Study site

    Naples

Other trials in Italy

Russia3 sites

  • Study site

    Kazan'

  • Study site

    Moscow

  • Study site

    Nizhny Novgorod

Other trials in Russia

Sweden2 sites

  • Study site

    Gothenburg

  • Study site

    Linköping

Other trials in Sweden

Finland1 site

  • Study site

    Vantaa

Other trials in Finland

About this study

Official title: A Double-Blind, Placebo-Controlled, Dose-Escalation, Parallel-Group Study to Evaluate the Efficacy and Safety of E2007 (Perampanel) Given as Adjunctive Therapy in Subjects With Refractory Partial Seizures

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.

Being tested
E2007 (perampanel), Placebo
Keywords
E2007 (perampanel), refractory partial seizures, adjunctive therapy, seizure frequency, reduction in seizure frequency, partial onset seizures, safety, concomitant AED(s)
Medical subject headings
Seizures

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • E2007 (perampanel)Drug

    Also called 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.

  • E2007 (perampanel)Drug

    Also called 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.

  • PlaceboDrug

    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.

Study groups in NCT00699582
Study groupRoleWhat they receive
1ExperimentalNot described
Receives: Drug: E2007 (perampanel)
2ExperimentalNot described
Receives: Drug: E2007 (perampanel)
3Placebo comparatorNot described
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline (Pre-randomization) through Week 19

Secondary outcomes (2)

  1. Responder Rate

    The responder rate for the Full ITT Analysis Set from the maintenance LOCF (Last Observation Carried Forward). A responder was a subject who had a 50 percent or greater reduction in seizure frequency per 28 days from the Pre-randomization phase.

    Measured: Baseline (Pre-randomization) through Week 19

  2. 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)

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

    Measured: Baseline (Pre-randomization) through Week 19

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jun 2008 (estimated)
  2. Study startMay 2008
  3. Primary completionDec 2010
  4. Study completionJan 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
389 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00699582
Sponsor's protocol ID
E2007-G000-305
Other IDs
2007-006168-31
Status last verified
Oct 2012
First submitted
17 Jun 2008
Last updated
11 Jul 2014

Publications

  • 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.

    PubMed 37059702

  • 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.

    PubMed 35305920

  • 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.

    PubMed 25878175

  • 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.

    PubMed 25823975

  • 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.

    PubMed 23663001

  • 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.

    PubMed 22905857

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing E2007 (perampanel) in people with Refractory Partial Seizures, run by Eisai Inc. at 92 sites in 14 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 92 sites in United States, Austria, France, Germany, Israel and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Nov 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change in the 28-day Seizure Frequency From Baseline to the End of the Double-blind Phase (Titration and Maintenance Phases) (time frame: Baseline (Pre-randomization) through Week 19). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00699582, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2014.

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