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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT00699972
First received: June 17, 2008
Last updated: January 2, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Refractory Partial Seizures
Drug: E2007 (perampanel)
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Seizure frequency per 28 days was derived from the information recorded in the subject diaries.


Secondary Outcome Measures:
  • Responder Rate [ Time Frame: Baseline (Pre-randomization) through Week 19 ] [ Designated as safety issue: No ]
    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.

  • 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) [ Time Frame: Baseline (Pre-randomization) through Week 19 ] [ Designated as safety issue: No ]
    Percent Change in the Seizure frequency per 28 days was derived from the information recorded in the subject diaries.


Enrollment: 390
Study Start Date: June 2008
Study Completion Date: November 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: 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.
Other Name: Perampanel
Experimental: 2 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.
Other Name: Perampanel
Placebo Comparator: 3 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.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00699972

  Hide Study Locations
Locations
United States, Alabama
Birmingham, Alabama, United States
United States, Arizona
St.Joseph's Hospital and Medical Center
Phoenix, Arizona, United States, 85013
United States, Arkansas
Clinical Trials, Inc.
Little Rock, Arkansas, United States, 72205
United States, Colorado
Mile High Research Center
Denver, Colorado, United States, 80218
United States, District of Columbia
Washington, District of Columbia, United States
United States, Florida
Jacksonville, Florida, United States, 32209
Loxahatchee, Florida, United States
Loxahatchee, Florida, United States, 33470
Pediatric Neurology, PA
Orlando, Florida, United States, 32819
North West Florida Clinical Research Group
Pensacola, Florida, United States, 32504
Lovelace Scientific Resources
Sarasota, Florida, United States, 34233
Tallahassee Neurological Clinic
Tallahassee, Florida, United States, 32308
Pediatric Epilepsy and Neurology Specialists
Tampa, Florida, United States, 33609
United States, Georgia
Children's Healthcare of Atlanta at Scottish Rite
Atlanta, Georgia, United States, 30342
Georgia Neurology and Sleep Medicine Associates
Suwanee, Georgia, United States, 30024
United States, Iowa
McFarland Clinic, PC
Ames, Iowa, United States, 50010
United States, Kansas
Via Christi Comprehensive Epilepsy Center
Wichita, Kansas, United States, 67214
Wichita, Kansas, United States
United States, Kentucky
Lexington, Kentucky, United States
Louisville, Kentucky, United States, 40202
United States, Louisiana
Houma, Louisiana, United States
Shreveport, Louisiana, United States
United States, Maryland
Baltimore, Maryland, United States, 21287
Mid-Atlantic Epilepsy and Sleep Center
Bethesda, Maryland, United States, 20817
United States, Michigan
Clinton Twp., Michigan, United States, 48035
United States, Missouri
St. Louis, Missouri, United States, 63110
United States, New York
Albany Medical College
Albany, New York, United States
Five Towns Neurology, PC
Cedarhurst, New York, United States, 11516
Long Island Jewish Medical Center
New Hyde Park, New York, United States
United States, North Carolina
Asheville Neurology Specialists, PA
Asheville, North Carolina, United States, 28806
United States, Ohio
Children's Hospital Medical Center of Akron d/b/a Akron Children's Hospital
Akron, Ohio, United States, 44308
The Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Toledo, Ohio, United States
United States, Oklahoma
Neurological Associates of Tulsa, Inc.
Tulsa, Oklahoma, United States, 74137
United States, Oregon
Portland, Oregon, United States
United States, Pennsylvania
Altoona, Pennsylvania, United States, 16602
Philadelphia, Pennsylvania, United States, 19107
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
Memphis, Tennessee, United States
United States, Texas
Dallas Pediatric Neurology Associates
Dallas, Texas, United States, 75230
Neurological Clinic of Texas, P.A.
Dallas, Texas, United States, 75230
Texas Tech University Health Sciences Center
El Paso, Texas, United States, 79905
Houston, Texas, United States
United States, Virginia
Richmond, Virginia, United States
United States, Washington
Seattle, Washington, United States, 98104
United States, Wisconsin
Milwaukee, Wisconsin, United States, 53215
Argentina
Capital Federal- Provincia de Buenos Aires., Argentina
Cordoba- Provincia de Cordoba, Argentina
Rosario - Provincia de Santa Fe, Argentina
Salta- Provincia de Salta, Argentina
Canada, Alberta
Calgary, Alberta, Canada
Canada, Ontario
London, Ontario, Canada
Youthdale Treatment Centers
Toronto, Ontario, Canada, M5B 1T9
Canada, Quebec
Neuro Rive-Sud
Greenfield Park, Quebec, Canada, J4V 2J2
Chile
Hospital Base Valdivia
Santiago, Chile
Santiago, Chile
Mexico
MIRC
Monterrey, Nuevo Leon, Mexico, 64000
Instituto Biomedico de Investigacion AC
Aguascalientes, Mexico, 20127
Medica Sur SIF-BIOTEC
Mexico City, Mexico, 14050
Hospital Central "Dr. Ignacio Morones Prieto"
San Luis Potosi, SLP, Mexico, 78240
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: David Squillacote, M.D. Eisai Inc.
  More Information

No publications provided by Eisai Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT00699972     History of Changes
Other Study ID Numbers: E2007-G000-304
Study First Received: June 17, 2008
Results First Received: October 23, 2012
Last Updated: January 2, 2013
Health Authority: United States: Food and Drug Administration; European Union: European Medicines Agency

Keywords provided by Eisai Inc.:
E2007
perampanel
refractory partial seizures
adjunctive therapy
seizure frequency
partial onset seizures
reduction in seizure frequency
safety
concomitant AED(s)

Additional relevant MeSH terms:
Seizures
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on July 24, 2014