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E2007 Given as Adjunctive Therapy in Patients With Refractory Partial Seizures

Primary Purpose

Epilepsy

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
E2007 (perampanel)
Placebo
Sponsored by
Eisai Inc.
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Epilepsy focused on measuring Epilepsy refractory partial seizures

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All Sexes

Inclusion Criteria: Provide written informed consent signed by patient or legal guardian prior to entering the study or undergoing any study procedures. Are reliable and willing to make themselves available for the study period and are able to record seizures and report adverse events themselves or have a caregiver who can record and report the events. Male and female patients will be eligible for enrollment. Females should be either of non-childbearing potential as a result of surgery, radiational therapy, menopause (one year post onset), or of childbearing potential and practicing a medically acceptable method of contraception (eg, abstinence, a barrier method plus spermicide, or intrauterine device [IUD]) for at least three months before Visit 1 (Screening) and for two months after the end of the study. They must also have a negative serum beta-human chorionic gonadotropin (beta-hCG) at Screening. Pregnant and/or lactating females are excluded. Those women using an oral contraceptive must also be using an additional approved method of contraception (eg, a barrier method plus spermicide, or IUD) starting with the Baseline Phase and continuing throughout the entire study period. Are between the ages of 18 and 70 years of age, inclusive. Are of 40 kg (88 lb) of weight or more. Have the diagnosis of epilepsy with partial-onset 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, electroencephalogram (EEG) and computed tomography/magnetic resonance imaging (CT/MRI) of the brain performed within the last 10 years and consistent with localization-related epilepsy. Have uncontrolled partial seizures despite having been treated with at least three different anti-epileptic drugs (AEDs) (given concurrently or sequentially) for at least 2 years. To be enrolled, patient must have averaged at least 4 partial seizures per month, with no 21-day seizure-free period during the 2 months preceding randomization. To be randomized, the patient must have had at least 3 seizures during the prospective Baseline Phase (28 days), with no 21-day seizure-free period. This should be documented in the form of medical history, medical records, or photocopied records of the patient diary/patient chart. Simple partial seizures without motor signs will not be counted towards this inclusion criterion. Are currently being treated with one or a maximum of two licensed AEDs and are known to take their medication(s) as directed. Are on a stable dose(s) of the same AED(s) for the 2 months prior to Visit 1. If using a vagal nerve stimulator, it must have been implanted for at least 5 months prior to Visit 1. Stimulator parameters may not be changed for at least 1 month prior to Visit 1 or thereafter during the study. Magnet use will be allowed and documented throughout the study. Exclusion Criteria: Have participated in a study involving administration of an investigational compound within one month of Visit 1 (Screening), or within 5 half-lives of the previous investigational compound, whichever is longer. Presence of non-motor simple partial seizures only. Presence of primary generalized epilepsies or seizures, such as absences, myoclonic epilepsies, Lennox-Gastaut syndrome. History of status epilepticus in the past year or seizure clusters where individual seizures cannot be counted. Show evidence of clinically significant disease (cardiac, respiratory, gastrointestinal, renal disease, etc) that in the opinion of the Investigator(s) could affect the patient's safety or trial conduct. Show 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 2 times the upper limit of normal (ULN). Show evidence of significant active hematological disease. White blood cell (WBC) count cannot be <= 2500/µL or an absolute neutrophil count <= 1000/µL. Clinically significant electrocardiogram (ECG) abnormality, including prolonged QTc defined as >= 450 msec for males and >= 470 msec for females. Presence of major active psychiatric disease. Patients taking a stable dose of selective serotonin reuptake inhibitor (SSRI) antidepressant will be allowed (except fluvoxamine). Presence of a progressive central nervous system (CNS) disease, including degenerative CNS diseases and tumors. Have a history of psychogenic seizures. Have a history of drug abuse and/or positive finding on urinary drug screening, other than prescribed medication. Have a history of alcohol abuse in the past 2 years, and/or positive finding on urinary drug screen. Have had multiple drug allergies (dermatological, hematological or organ toxicity) or one or more severe drug reactions. Allergy to lactose. Concomitant use of felbamate or use of felbamate within 2 months prior to Visit 1. Concomitant use of vigabatrin. Patients that took vigabatrin in the past must be off vigabatrin for at least 5 months prior to Visit 1 and must not have evidence of a clinically significant abnormality in a visual perimetry test. Concomitant use or use within the previous 4 weeks prior to Visit 1 of neuroleptics, monoamine oxidase (MAO) inhibitors, barbiturates (except for seizure control indication), benzodiazepines (other than occasional intermittent use), and narcotic analgesics. Frequent need of rescue benzodiazepines (one or more times a month).

Sites / Locations

  • Dept. of Neuro Surgery
  • USF Physicians Group
  • Clinical Trials
  • Medical College of Ohio Comprehensive Epilepsy Ctr.
  • Vanderbilt University Medical Ctr.

Outcomes

Primary Outcome Measures

To determine the maximum tolerated dose (MTD) of E2007 given bid or qd in patients with refractory partial-onset seizures (including secondarily generalized seizures)

Secondary Outcome Measures

To evaluate the safety, efficacy, and concentration-efficacy relationship

Full Information

First Posted
September 1, 2005
Last Updated
November 2, 2015
Sponsor
Eisai Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00144690
Brief Title
E2007 Given as Adjunctive Therapy in Patients With Refractory Partial Seizures
Official Title
A Double-Blind, Placebo-Controlled, Dose-Escalation, Parallel-Group Study of E2007 Given as Adjunctive Therapy in Patients With Refractory Partial Seizures
Study Type
Interventional

2. Study Status

Record Verification Date
November 2015
Overall Recruitment Status
Completed
Study Start Date
March 2005 (undefined)
Primary Completion Date
February 2007 (Actual)
Study Completion Date
February 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eisai Inc.

4. Oversight

5. Study Description

Brief Summary
The primary objective of this study is to determine the maximal tolerated dose (MTD) of E2007 given twice daily (bid) or once a day (qd) in patients with refractory partial-onset seizures (including secondarily generalized seizures). The secondary objectives are to evaluate the safety, efficacy, concentration-efficacy relationship, and pharmacokinetics of E2007 and the effects of E2007 on the Profile of Mood States (POMS) test.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epilepsy
Keywords
Epilepsy refractory partial seizures

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
E2007 (perampanel)
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
To determine the maximum tolerated dose (MTD) of E2007 given bid or qd in patients with refractory partial-onset seizures (including secondarily generalized seizures)
Secondary Outcome Measure Information:
Title
To evaluate the safety, efficacy, and concentration-efficacy relationship

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Eligibility Criteria
Inclusion Criteria: Provide written informed consent signed by patient or legal guardian prior to entering the study or undergoing any study procedures. Are reliable and willing to make themselves available for the study period and are able to record seizures and report adverse events themselves or have a caregiver who can record and report the events. Male and female patients will be eligible for enrollment. Females should be either of non-childbearing potential as a result of surgery, radiational therapy, menopause (one year post onset), or of childbearing potential and practicing a medically acceptable method of contraception (eg, abstinence, a barrier method plus spermicide, or intrauterine device [IUD]) for at least three months before Visit 1 (Screening) and for two months after the end of the study. They must also have a negative serum beta-human chorionic gonadotropin (beta-hCG) at Screening. Pregnant and/or lactating females are excluded. Those women using an oral contraceptive must also be using an additional approved method of contraception (eg, a barrier method plus spermicide, or IUD) starting with the Baseline Phase and continuing throughout the entire study period. Are between the ages of 18 and 70 years of age, inclusive. Are of 40 kg (88 lb) of weight or more. Have the diagnosis of epilepsy with partial-onset 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, electroencephalogram (EEG) and computed tomography/magnetic resonance imaging (CT/MRI) of the brain performed within the last 10 years and consistent with localization-related epilepsy. Have uncontrolled partial seizures despite having been treated with at least three different anti-epileptic drugs (AEDs) (given concurrently or sequentially) for at least 2 years. To be enrolled, patient must have averaged at least 4 partial seizures per month, with no 21-day seizure-free period during the 2 months preceding randomization. To be randomized, the patient must have had at least 3 seizures during the prospective Baseline Phase (28 days), with no 21-day seizure-free period. This should be documented in the form of medical history, medical records, or photocopied records of the patient diary/patient chart. Simple partial seizures without motor signs will not be counted towards this inclusion criterion. Are currently being treated with one or a maximum of two licensed AEDs and are known to take their medication(s) as directed. Are on a stable dose(s) of the same AED(s) for the 2 months prior to Visit 1. If using a vagal nerve stimulator, it must have been implanted for at least 5 months prior to Visit 1. Stimulator parameters may not be changed for at least 1 month prior to Visit 1 or thereafter during the study. Magnet use will be allowed and documented throughout the study. Exclusion Criteria: Have participated in a study involving administration of an investigational compound within one month of Visit 1 (Screening), or within 5 half-lives of the previous investigational compound, whichever is longer. Presence of non-motor simple partial seizures only. Presence of primary generalized epilepsies or seizures, such as absences, myoclonic epilepsies, Lennox-Gastaut syndrome. History of status epilepticus in the past year or seizure clusters where individual seizures cannot be counted. Show evidence of clinically significant disease (cardiac, respiratory, gastrointestinal, renal disease, etc) that in the opinion of the Investigator(s) could affect the patient's safety or trial conduct. Show 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 2 times the upper limit of normal (ULN). Show evidence of significant active hematological disease. White blood cell (WBC) count cannot be <= 2500/µL or an absolute neutrophil count <= 1000/µL. Clinically significant electrocardiogram (ECG) abnormality, including prolonged QTc defined as >= 450 msec for males and >= 470 msec for females. Presence of major active psychiatric disease. Patients taking a stable dose of selective serotonin reuptake inhibitor (SSRI) antidepressant will be allowed (except fluvoxamine). Presence of a progressive central nervous system (CNS) disease, including degenerative CNS diseases and tumors. Have a history of psychogenic seizures. Have a history of drug abuse and/or positive finding on urinary drug screening, other than prescribed medication. Have a history of alcohol abuse in the past 2 years, and/or positive finding on urinary drug screen. Have had multiple drug allergies (dermatological, hematological or organ toxicity) or one or more severe drug reactions. Allergy to lactose. Concomitant use of felbamate or use of felbamate within 2 months prior to Visit 1. Concomitant use of vigabatrin. Patients that took vigabatrin in the past must be off vigabatrin for at least 5 months prior to Visit 1 and must not have evidence of a clinically significant abnormality in a visual perimetry test. Concomitant use or use within the previous 4 weeks prior to Visit 1 of neuroleptics, monoamine oxidase (MAO) inhibitors, barbiturates (except for seizure control indication), benzodiazepines (other than occasional intermittent use), and narcotic analgesics. Frequent need of rescue benzodiazepines (one or more times a month).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Santiago Arroyo, M.D., Ph.D.
Organizational Affiliation
Eisai Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Dept. of Neuro Surgery
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
USF Physicians Group
City
Tampa
State/Province
Florida
ZIP/Postal Code
33606
Country
United States
Facility Name
Clinical Trials
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Medical College of Ohio Comprehensive Epilepsy Ctr.
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43614
Country
United States
Facility Name
Vanderbilt University Medical Ctr.
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21883097
Citation
Krauss GL, Bar M, Biton V, Klapper JA, Rektor I, Vaiciene-Magistris N, Squillacote D, Kumar D. Tolerability and safety of perampanel: two randomized dose-escalation studies. Acta Neurol Scand. 2012 Jan;125(1):8-15. doi: 10.1111/j.1600-0404.2011.01588.x. Epub 2011 Aug 29.
Results Reference
result
PubMed Identifier
35305920
Citation
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.
Results Reference
derived

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E2007 Given as Adjunctive Therapy in Patients With Refractory Partial Seizures

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