E2007 Given as Adjunctive Therapy in Patients With Refractory Partial Seizures

• Register: ClinicalTrials.gov
• Last refreshed on: 20 May 2013
• Main ID: NCT00144690
• Date of registration: 01/09/2005
• Primary sponsor: Eisai Inc.
• Public title: E2007 Given as Adjunctive Therapy in Patients With Refractory Partial Seizures
• Scientific title: A Double-Blind, Placebo-Controlled, Dose-Escalation, Parallel-Group Study of E2007 Given as Adjunctive Therapy in Patients With Refractory Partial Seizures
• Date of first enrolment: March 2005
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00144690
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Santiago Arroyo, M.D., Ph.D.
• Affiliation: Eisai Inc.

Key inclusion & exclusion 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).



Age minimum: 18 Years
Age maximum: 70 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Epilepsy

Intervention(s)

Drug: E2007 (perampanel)

Drug: Placebo

Primary Outcome(s)

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(s)

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

Secondary ID(s)

E2007-A001-206

Source(s) of Monetary Support

Please refer to primary and secondary sponsors