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

NCT01393743 | Completed Phase 3 Results

• 1 other identifier: E2007-G000-332
• Study Type: interventional
• Target: 163
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Seizure Disorder Generalized Tonic Clonic

Keywords

Central Nervous System

Outcome Measures

Primary Outcomes (3)

• Median Percent Change in Primary Generalized Tonic Clonic Seizure Frequency (PGTC) Per 28 Days During the Titration and Maintenance Periods (Combined) Relative to Baseline (Prerandomization) - (for Core Study)

  Seizure frequency per 28 days was derived from the information recorded in the participant diaries. PGTC seizure frequency per 28 days (as determined from participant diaries) was calculated as the number of PGTC seizures divided by the number of days in the interval and multiplied by 28. The percent change from baseline in PGTC seizure was analyzed over the Titration and Maintenance Periods combined, while baseline was defined as seizure frequency per 28 days based on all valid diary data during the Prerandomization Phase.

  Baseline (4 or 8 weeks), Titration (4 weeks), and Maintenance (13 weeks)

• 50% Responder Rate for Primary Generalized Tonic Clonic Seizure During Maintenance - LOCF - (for Core Study)

  A responder was a participant who experienced a 50% or greater reduction in seizure frequency per 28 days during Maintenance-last observation carried forward (LOCF) from prerandomization. The data was presented as the percentage of participants.

  Baseline (4 or 8 weeks) and Maintenance (13 weeks)

• 50% Responder Rate in Primary Generalized Tonic-Clonic Seizure Frequency Per 28 Days Relative to the Core Study Prerandomization Phase - (for Extension Phase)

  Responder rate was defined as the percentage of participants who experienced a 50% or greater reduction in PGTC and total seizure frequency during treatment per 28 days relative to baseline (responder). Week 1 began on the date of first dose of the perampanel treatment regardless of whether it occurred in the Core Study or Extension Phase and continued to and included the date of the last dose of perampanel in the Extension Phase. For any given analysis window and seizure type(s), a 50% response from Core Study Prerandomization is a participant whose seizure frequency per 28 days for that seizure type(s) during that analysis window is 50% to 100% lower than his or her Core Study Prerandomization baseline seizure frequency per 28 days for that same seizure type(s). In Part B of the Extension Phase (after Visit 15), the seizure diary is only completed for days on which a seizure occurred and missing days were imputed as non-seizure days.

  Week 1 of perampanel treatment to date of last dose of perampanel in the Extension Phase

Secondary Outcomes (7)

• Median Percent Change in All Seizure Frequency Per 28 Days During the Titration and Maintenance Periods (Combined) Relative to Baseline (Prerandomization) - (for Core Study)

  Baseline (4 or 8 weeks), Titration (4 weeks), and Maintenance (13 weeks)

• Median Percent Change in Primary Generalized Seizure Subtype Frequency Per 28 Days During the Titration and Maintenance Periods (Combined) Relative to Baseline (Prerandomization) - (for Core Study)

  Baseline (4 or 8 weeks), Titration (4 weeks), and Maintenance (13 weeks)

• 50% Responder Rate for All Seizures During Maintenance-LOCF - (for Core Study)

  Baseline (4 or 8 weeks) and Maintenance (13 weeks)

• 50% Responder Rate for Primary Generalized Seizure Subtype During Maintenance Period - LOCF - (for Core Study)

  Baseline (4 or 8 weeks) and Maintenance (13 weeks)

• Percent Change From Core Study Prerandomization Phase in Primary Generalized Tonic-Clonic (PGTC) Seizure Frequency Per 28 Days - (for Extension Phase)

  Date of first dose of study drug to date of last dose of study drug in the Extension Phase

Study Arms (2)

Perampanel

EXPERIMENTAL

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.

Drug: Perampanel

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo comparator

Interventions

Perampanel DRUG

Also known as: E2007

Perampanel

Placebo comparator DRUG

Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• 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
• 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).
• 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 participant has been on this diet for 5 weeks prior to randomization

You may not qualify if:

• 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
• Concomitant diagnosis of Partial Onset Seizures (POS)
• Progressive neurological disease
• Clinical diagnosis of Lennox-Gastaut syndrome
• 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.
• 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
• 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) two or more times within the 30 days prior to Baseline

Sponsors & Collaborators

• Eisai Inc.: lead

Related Publications (2)

• 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.

  PMID: 36106379 DERIVED

• 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.

  PMID: 26296511 DERIVED

MeSH Terms

Interventions

perampanel

Results Point of Contact

• Title: Eisai Medical Services
• Organization: Eisai, Inc.

esi_medinfo@eisai.com

1-888-422-4743

Study Officials

• Francesco Bibbiani

  Eisai Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2011
• First Posted: July 13, 2011
• Study Start: September 1, 2011
• Primary Completion: May 1, 2014
• Study Completion: November 1, 2015
• Last Updated: August 28, 2017
• Results First Posted: January 11, 2016

Record last verified: 2017-07