4-Year Open-Label Extension Phase of the Parallel-Group Study of E2007 in Patients With Refractory Partial Seizures

An Open-Label Extension Phase of the Double-Blind, Placebo-Controlled, Dose-Escalation, Parallel-Group Study of E2007 (Perampanel) as an Adjunctive Therapy in Patients With Refractory Partial Seizures

The purpose of this study is to determine the safety of perampanel given as adjunctive, long-term treatment in patients with refractory partial onset seizures.

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: Perampanel

Detailed Description

This is an Open-Label Extension (OLE) study for patients who completed the E2007-A001-206 (NCT00144690) or the E2007-G000-208 (NCT00416195) double-blind, placebo-controlled, dose-escalation, parallel-group studies.

This study consisted of 3 periods: OLE Titration (12 weeks), OLE Maintenance (424 weeks), and OLE Follow-up (4 weeks). During the OLE Titration Period, participants were titrated to their maximum tolerated dose (MTD) of perampanel, up to a maximum of 12 mg/day. The OLE Maintenance Period began at completion of the OLE Titration Period; participants remained on the dose achieved at the end of the OLE Titration Period unless dose adjustment for tolerability reasons was necessary. Participants who either withdrew from the study prematurely or completed the OLE Maintenance Period returned for a final visit at the end of the 4-week OLE Follow-up Period.

• Study Type: Interventional
• Enrollment (Actual): 138
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Chatswood, New South Wales, Australia, 2067
  • Queensland
    • Maroochydore, Queensland, Australia, 4558
  • South Australia
    • Woodville, South Australia, Australia, 5011
• Belgium
  • Edegem, Belgium, 2650
  • Gent, Belgium, 9000
  • Leuven, Belgium, B-3000
  • Tielt, Belgium, B-8700
• Czech Republic
  • Brno, Czech Republic, 656 91
  • Hradec Kralove, Czech Republic, 500 05
  • Olomouc, Czech Republic, 775 20
  • Ostrava, Czech Republic, 708 52
  • Praha 5, Czech Republic, 150 06
  • Rychnov nad Kneznou, Czech Republic, 516 01
• Estonia
  • Tallinn, Estonia, 10617
  • Tartu, Estonia, EE-51014
• Finland
  • Kuopio, Finland, FI-70210
  • Tampere, Finland, FI-33520
• France
  • Lille, France, 59037
  • Montpellier, France, 34295
  • Ramonville Saint-Agne, France, 31520
• Germany
  • Berlin, Germany, D-10365
  • Gottingen, Germany, 37075
  • Munchen, Germany, 80333
  • Ulm, Germany, 89081
• Latvia
  • Riga, Latvia, LV-1002
• Lithuania
  • Kaunas, Lithuania, LT-50009
  • Kaunas, Lithuania, LT-50185
  • Klaipeda, Lithuania, LT-92288
  • Siauliai, Lithuania, LT-76231
  • Vilnius, Lithuania, LT-08661
  • Vilnius, Lithuania, LT-03215
• Netherlands
  • Rotterdam, Netherlands, 3012 KM
• Spain
  • Valencia, Spain, 46009
• Sweden
  • Stockholm, Sweden, 112 45
• United Kingdom
  • Dundee, United Kingdom, DD1 9SY
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
  • Arizona
    • Phoenix, Arizona, United States, 85013
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
  • Colorado
    • Denver, Colorado, United States, 80218
  • Florida
    • Bradenton, Florida, United States, 34205
    • Melbourne, Florida, United States, 32901
  • Georgia
    • Atlanta, Georgia, United States, 30322
  • Maryland
    • Baltimore, Maryland, United States, 21287
  • New York
    • New Hyde Park, New York, United States, 11040
  • Ohio
    • Columbus, Ohio, United States, 43210
  • Utah
    • West Jordan, Utah, United States, 84088
  • Vermont
    • Burlington, Vermont, United States, 05401

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

KEY INCLUSION CRITERIA:

1. Have completed all scheduled visits up to and including Visit 8 in the E2007-A001-206 (NCT00144690) study or Visit 9 of the E2007-G000-208 (NCT00416195) study.
2. 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.
3. Females of childbearing potential must continue practicing a medically acceptable method of contraception (e.g., abstinence, a barrier method plus spermicide, or Intrauterine device (IUD)) and for 8 weeks after the end of the OLE study. Those women using hormonal contraceptives must also continue using an additional approved method of contraception (e.g., a barrier method plus spermicide, or IUD).
4. Are between the ages of 18 and 70 years of age, inclusive.
5. Are at least 40 kg (88 lb) of weight.
6. Are currently being treated with a stable dose of one, or a maximum of three licensed Anti-epileptic drugs (AEDs) and are known to take their medication(s) as directed.

KEY EXCLUSION CRITERIA:

1. Show evidence of clinically significant disease (cardiac, respiratory, gastrointestinal, renal disease, etc.,) that, in the opinion of the Investigator(s), could affect the participant's safety or trial conduct.
2. Show evidence of significant active hepatic disease and/or bilirubin greater than 1.5 mg/dL. 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 two times the upper limit of normal (ULN).
3. Show evidence of significant active hematological disease. White blood cell (WBC) count cannot be less than or equal to 2500/microL or an absolute neutrophil count less than or equal to 1000/microL.
4. Clinically significant ECG abnormality, including prolonged QTc (defined as greater than or equal to 450 msec).
5. Presence of major active psychiatric disease. Participants taking a stable dose of selective serotonin reuptake inhibitor (SSRI) antidepressant will be allowed.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Perampanel; Participants previously receiving placebo/perampanel in the double blind study, were titrated to receive perampanel 2 mg to 12 mg, once daily during the OLE study	Drug: Perampanel; Perampanel 2 mg to 12 mg, once daily during the OLE study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Non-serious Adverse Events (AEs) and Treatment-emergent Serious Adverse Events (SAEs)	An AE was defined as any untoward medical occurrence in a clinical investigation participant administered an investigational product. A SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening (ie, the participant was at immediate risk of death from the AE as it occurred; this did not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was as a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug). In this study, treatment emergent AEs (defined as an AE (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) were assessed. The data is presented in the safety section of the results.	From date of first dose of perampanel up to 30 days after the last dose of perampanel or up to approximately 8 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Seizure Frequency Per 28 Days Relative to Pre-Perampanel Baseline	Seizure frequency was derived from information (seizure count and type) recorded in participant diary. The seizure frequency per 28 days was calculated as the number of seizures divided by the number of days in the interval and multiplied by 28. The percent change in 28-day seizure frequency from baseline was assessed for all partial-onset seizures types. For participants who had been assigned to treatment with perampanel (previous treatment), pre-perampanel Baseline referred to the Prerandomization Phase of the Core Double Blind study. For participants who had been assigned to treatment with placebo (previous treatment), pre-perampanel Baseline was computed from all data during the Core Double Blind study (including Prerandomization Phase) prior to treatment with perampanel.	Baseline up to Week 221
Percentage of Participants Who Experienced a 50% or Greater Reduction in Seizure Frequency Per 28 Days Relative to the Pre-perampanel Baseline	Seizure frequency was derived from information (seizure count and type) recorded in participant diary. The percentage of participants who experienced a 50% or greater reduction in seizure frequency per 28 days relative to the pre-perampanel Baseline (responders) was assessed. For participants who had been assigned to treatment with perampanel (previous treatment), pre-perampanel Baseline referred to the Prerandomization Phase of the Core Double Blind study. For participants who had been assigned to treatment with placebo (previous treatment), pre-perampanel Baseline was computed from all data during the Core Double Blind study (including Prerandomization Phase) prior to treatment with perampanel. The data is presented as percent responders.	Baseline up to week 221

Collaborators and Investigators

• Sponsor: Eisai Inc.

Publications and helpful links

General Publications

• 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.
• Rektor I, Krauss GL, Bar M, Biton V, Klapper JA, Vaiciene-Magistris N, Kuba R, Squillacote D, Gee M, Kumar D. Perampanel Study 207: long-term open-label evaluation in patients with epilepsy. Acta Neurol Scand. 2012 Oct;126(4):263-9. doi: 10.1111/ane.12001. Epub 2012 Aug 23.

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: August 22, 2006
• First Submitted That Met QC Criteria: August 22, 2006
• First Posted (Estimate): August 24, 2006

Study Record Updates

• Last Update Posted (Estimate): December 10, 2015
• Last Update Submitted That Met QC Criteria: November 5, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Refractory; Seizures; Partial
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Seizures
• Other Study ID Numbers: E2007-A001-207