A research study to find out if people with Primary Generalized Tonic-Clonic Seizures, by taking perampanel in addition to their normal epilepsy medicine(s), have fewer seizures and feel better. Either perampanel (real medicine) or placebo (pretend medicine that looks the same as the real medicine) will be given in addition to ordinary epilepsy medicines. Who gets which is decided randomly. There is an option to continue into the Follow-on (Extension) Phase of the study.

• Register: EUCTR
• Last refreshed on: 11 April 2016
• Main ID: EUCTR2011-000265-12-DE
• Date of registration: 05/07/2011
• Prospective Registration: Yes
• Primary sponsor: Eisai Limited
• Public title: A research study to find out if people with Primary Generalized Tonic-Clonic Seizures, by taking perampanel in addition to their normal epilepsy medicine(s), have fewer seizures and feel better. Either perampanel (real medicine) or placebo (pretend medicine that looks the same as the real medicine) will be given in addition to ordinary epilepsy medicines. Who gets which is decided randomly. There is an option to continue into the Follow-on (Extension) Phase of the study.
• Scientific title: A Double-blind, Randomized, Placebo-controlled, Multicenter, Parallel-group Study with an Open-label Extension Phase to Evaluate the Efficacy and Safety of Adjunctive Perampanel in Primary Generalized Tonic-Clonic Seizures
• Date of first enrolment: 01/12/2011
• Target sample size: 164
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-000265-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Australia, Austria, China, Czech Republic, Estonia, France, Germany, Greece, Hungary, India, Israel, Japan, Korea, Republic of, Latvia, Lithuania, Netherlands, Poland, Serbia, Thailand, United States

Contacts

• Name: Medical Information
• Affiliation: Eisai Ltd.

• Name: Medical Information
• Affiliation: Eisai Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
• Ages 12 years and older (in Germany, greater than or equal to 18 years of age [within the course of the study] at the time of the informed
consent; in India, less than 65 years)

• Clinical diagnosis of PGTC seizures in the setting of idiopathic generalized epilepsy (with or without other subtypes of primary generalized seizures) and experiencing = 3 PGTC seizures during the 8-week period prior to randomization

• Have had a routine electroencephalogram (EEG) up to 5 years prior to or during the Baseline Period with electroencephalographic features consistent with primary generalized epilepsy (also called idiopathic generalized epilepsy); other concomitant anomaly should be explained by adequate past medical history. In the case of a normal historical EEG,
EEG should be repeated. In the case of another normal EEG upon repeat, the presence or history of myoclonus or typical absence seizure, or first degree relative with PGTC seizures, is required. If the repeat EEG presents abnormalities compatible with PGTC seizures, no further action is required and the subject is eligible for enrollment.

• On a fixed dose of one to a maximun of three concomitant AEDs for a minimum of 30 days prior to Baseline; only one inducer AED (i.e., carbamazepine, oxcarbazepine, or phenytoin) out of the maximum of three AEDs will be allowed

• A vagal nerve stimulator (VNS) will be allowed, but it must have been implanted = 5 months prior to Baseline (stimulator parameters can not be changed for 30 days prior to Baseline and for the duration of the study)

• Have had a computed tomography (CT) or magnetic resonance imaging (MRI) within the last 10 years (for adults) and 5 years (for adolescents) that ruled out a progressive cause of epilepsy

• A ketogenic diet will be allowed as long as the subject has been on this diet for 5 weeks prior to randomization
Are the trial subjects under 18? yes
Number of subjects for this age range: 66
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 82
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 16

Exclusion criteria:
• Participated in a study involving administration of an investigational compound or device within the 30 days prior to Baseline, or within approximately 5 half-lives of the previous investigational compound, whichever is longer

• Pregnant and/or nursing

• Participated in previous perampanel studies

• A history of status epilepticus that required hospitalization within 12 months prior to Baseline

• Seizure clusters where individual seizures cannot be counted

• A history of psychogenic seizures

• Any suicidal ideation with intent with or without a plan at or within 6 months prior to Visit 2 (i.e., answering “Yes” to questions 4 or 5 on the Suicidal Ideation section of the Columbia-Suicide Severity Rating Scale (C-SSRS)

• Evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator(s) could affect the subject’s safety or study conduct

• Concomitant diagnosis of Partial Onset Seizures (POS)

• Progressive neurological disease

• Clinical diagnosis of Lennox-Gastaut syndrome

• History of drug or alcohol dependency or abuse within 2 years prior to Screening

• Have had multiple drug allergies or a severe drug reaction to an AED(s), including dermatological (e.g., 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 60 days prior to Baseline. They must not have a history of white blood cell (WBC) count below = 2500/µL (2.50 1E+09/L), platelets < 100,000/µL, liver function tests (LFTs) > 3 times the upper limit of normal (ULN), or other indication of hepatic or bone marrow dysfunction while receiving felbamate.

• Concomitant use of vigabatrin: Subjects who took vigabatrin in the past must be discontinued for approximately 5 months prior to Baseline, and must have documentation showing no evidence of a vigabatrin-associated clinically significant abnormality in an automated visual perimetry test

• Concomitant use of medications known to be inducers of CYP3A (with the exception of carbamazepine, oxcarbazepine, and phenytoin) including, but not limited to: rifampin, troglitazone, St John's Wort, efavirenz, nevirapine, glucocorticoids (other than topical usage), modafinil, pioglitazone, and rifabutin within 30 days prior to Baseline.
Concomitant use of barbiturates (except for seizure control indication) within 30 days prior to Baseline. Concomitant use of barbiturates (except for seizure control indication) within 30 days prior to Baseline.

• Use of intermittent rescue benzodiazepines (i.e., one to two doses over a 24-hour period considered one-time rescue) more than two times within the 30 days prior to Baseline

• Subjects with active viral hepatitis (A, B, or C) as demonstrated by pre-existing positive serology

• 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)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Primary Generalized Tonic-Clonic Seizures
MedDRA version: 16.1 Level: HLT Classification code 10018101 Term: Generalised tonic-clonic seizures System Organ Class: 100000004852

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: perampanel
Product Code: E2007
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Perampanel
Current Sponsor code: E2007
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: perampanel
Product Code: E2007
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Perampanel
Current Sponsor code: E2007
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-

Primary Outcome(s)

Primary end point(s): • Percent Change in PGTC Seizure Frequency
(Except for the purpose of registration in the European Union (EU), where this endpoint will be the key secondary endpoint)

• Responder Rate: (For the purpose of EU registration, this endpoint will be the key secondary endpoint or other purposes)
A responder is defined as a subject who experiences a = 50% reduction in PGTC seizure frequency.

Secondary Objective: - To evaluate the safety and tolerability of perampanel in subjects with inadequately controlled PGTC seizures
- To evaluate the efficacy of adjunctive perampanel therapy, compared
to placebo on other subtypes of primary generalized seizure (myoclonic,
absence, and all seizures)

Timepoint(s) of evaluation of this end point: • PGTC seizure frequency per 28 days during treatment: The percent change from baseline will be analyzed over the Titration and Maintenance Periods combined in the Full Analysis Set(FAS). The baseline is defined as seizure frequency per 28 days based on all valid diary data during the Prerandomization Phase.

• Responder Rate: In the Maintenance Period relative to baseline in the FAS.

Main Objective: To demonstrate the efficacy of adjunctive perampanel therapy, compared to placebo, on primary generalized tonic-clonic (PGTC) seizures

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: • Percent change in all subtypes of primary generalized seizure frequency:
Per 28 days in the Titration and Maintenance Periods combined relative to baseline will be analyzed using rank ANCOVA in the FAS

• Responder Rate for all subtypes of primary generalized seizure frequency:
Per 28 days in the Maintenance Period relative to baseline will be analyzed based on a CMH test in the FAS.

Secondary end point(s): Other secondary efficacy endpoints will be analyzed as follows:

• Percent change in all subtypes of primary generalized seizure frequency

• Responder Rate for all subtypes of primary generalized seizure frequency

Secondary ID(s)

2011-000265-12-HU

E2007-G000-332

Source(s) of Monetary Support

Eisai Inc.