A Efficacy and Safety Study of Adjunctive Perampanel in Primary Generalized Tonic Clonic Seizures

NCT ID: NCT01393743

Last Updated: 2017-08-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 163 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2015-11-30

Brief Summary

This study is designed to evaluate the efficacy, safety, and pharmacokinetics (PK) of perampanel on Primary Generalized Tonic Clonic (PGTC) seizure frequency in adolescents and adults maintained on one to two stable antiepileptic drugs (AED).

Detailed Description

This study is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, adjunctive-therapy study with an open-label Extension Phase. The Core Study consists of 2 phases: Prerandomization and Randomization. The Prerandomization Phase consisted of 2 periods: Screening (up to 4 weeks) and Baseline (4 or 8 weeks, depending on the accuracy of diary-documented seizures during Screening), during which participants will be assessed for eligibility to participate in the study. The Randomization Phase consisted of 3 periods: Titration (4 weeks), Maintenance (13 weeks), and Follow-up (4 weeks; only for those participants not entering into the Extension Phase). At the start of the Randomization Phase, eligible participants will be randomized to the perampanel or placebo treatment groups in a 1:1 ratio. The extension phase consists of 142 weeks.

Conditions

Seizure Disorder Generalized Tonic Clonic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Perampanel

Participants received 6 tablets (initially 1 tablet of 2-mg perampanel plus 5 tablets of perampanel matched placebo) and up-titrated weekly in 2-mg increments to a target dose range of 8 mg per day maintaining the blind with administration of 6 tablets per day of either perampanel/placebo.

Group Type: EXPERIMENTAL

Perampanel

Intervention Type: DRUG

Placebo

Participants received 6 tablets of perampanel matched placebo, once a day.

Group Type: PLACEBO_COMPARATOR

Placebo comparator

Intervention Type: DRUG

Interventions

Perampanel

Intervention Type: DRUG

Placebo comparator

Intervention Type: DRUG

Other Intervention Names

E2007

Eligibility Criteria

Inclusion Criteria

1. Clinical diagnosis of PGTC seizures (with or without other subtypes of primary generalized seizures) and experiencing greater than or equal to 3 PGTC seizures during the 8-week period prior to randomization

2. Have had a routine electroencephalogram (EEG) prior to or during the Baseline Period with electroencephalographic features consistent with primary generalized epilepsy; other concomitant anomaly should be explained by adequate past medical history

3. On a fixed dose of one to a maximum of three concomitant antiepileptic drugs (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 two AEDs will be allowed

4. A vagal nerve stimulator (VNS) will be allowed, but it must have been implanted greater than or equal to 5 months prior to Baseline (stimulator parameters cannot be changed for 30 days prior to Baseline and for the duration of the study).

5. 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

6. A ketogenic diet will be allowed as long as the participant has been on this diet for 5 weeks prior to randomization

Exclusion:

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

2. Seizure clusters where individual seizures cannot be counted

3. A history of psychogenic seizures

4. Concomitant diagnosis of Partial Onset Seizures (POS)

5. Progressive neurological disease

6. Clinical diagnosis of Lennox-Gastaut syndrome

7. If felbamate is used as a concomitant AED, participants 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 less than or equal to 2500/microL (2.50 1E+09/L), platelets less than 100,000/microL, liver function tests (LFTs) greater than 3 times the upper limit of normal (ULN), or other indication of hepatic or bone marrow dysfunction while receiving felbamate.

8. Concomitant use of vigabatrin: Participants 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

9. Concomitant use of barbiturates (except for seizure control indication) within 30 days prior to Baseline

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

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eisai Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francesco Bibbiani

Role: STUDY_DIRECTOR

Eisai Inc.

References

Kerr WT, Brandt C, Ngo LY, Patten A, Cheng JY, Kramer L, French JA. Time to exceed pre-randomization monthly seizure count for perampanel in participants with primary generalized tonic-clonic seizures: A potential clinical end point. Epilepsia. 2022 Nov;63(11):2994-3004. doi: 10.1111/epi.17411. Epub 2022 Sep 30.

Reference Type: DERIVED

PMID: 36106379 (View on PubMed)

French JA, Krauss GL, Wechsler RT, Wang XF, DiVentura B, Brandt C, Trinka E, O'Brien TJ, Laurenza A, Patten A, Bibbiani F. Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy A randomized trial. Neurology. 2015 Sep 15;85(11):950-7. doi: 10.1212/WNL.0000000000001930.

Reference Type: DERIVED

PMID: 26296511 (View on PubMed)

Other Identifiers

E2007-G000-332

Identifier Type: -

Identifier Source: org_study_id