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

• ClinicalTrials.gov Identifier: NCT00368472
• Recruitment Status: Completed
• First Posted: August 24, 2006
• Results First Posted: December 10, 2015
• Last Update Posted: December 10, 2015
• Sponsor: Eisai Inc.
• Information provided by (Responsible Party): Eisai Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Epilepsy	Drug: Perampanel	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 138 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: October 2006
• Actual Primary Completion Date: June 2014
• Actual Study Completion Date: July 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Treatment-emergent Non-serious Adverse Events (AEs) and Treatment-emergent Serious Adverse Events (SAEs) [ Time Frame: From date of first dose of perampanel up to 30 days after the last dose of perampanel or up to approximately 8 years ]
   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.

Secondary Outcome Measures :

1. Percent Change in Seizure Frequency Per 28 Days Relative to Pre-Perampanel Baseline [ Time Frame: Baseline up to Week 221 ]
   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.
2. Percentage of Participants Who Experienced a 50% or Greater Reduction in Seizure Frequency Per 28 Days Relative to the Pre-perampanel Baseline [ Time Frame: Baseline up to week 221 ]
   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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Alabama

Birmingham, Alabama, United States, 35294

United States, Arizona

Phoenix, Arizona, United States, 85013

United States, Arkansas

Little Rock, Arkansas, United States, 72205

United States, Colorado

Denver, Colorado, United States, 80218

United States, Florida

Bradenton, Florida, United States, 34205

Melbourne, Florida, United States, 32901

United States, Georgia

Atlanta, Georgia, United States, 30322

United States, Maryland

Baltimore, Maryland, United States, 21287

United States, New York

New Hyde Park, New York, United States, 11040

United States, Ohio

Columbus, Ohio, United States, 43210

United States, Utah

West Jordan, Utah, United States, 84088

United States, Vermont

Burlington, Vermont, United States, 05401

Australia, New South Wales

Chatswood, New South Wales, Australia, 2067

Australia, Queensland

Maroochydore, Queensland, Australia, 4558

Australia, 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-03215

Vilnius, Lithuania, LT-08661

Netherlands

Rotterdam, Netherlands, 3012 KM

Spain

Valencia, Spain, 46009

Sweden

Stockholm, Sweden, 112 45

United Kingdom

Dundee, United Kingdom, DD1 9SY

Sponsors and Collaborators

Eisai Inc.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Eisai Inc.
• ClinicalTrials.gov Identifier: NCT00368472
• Other Study ID Numbers: E2007-A001-207
• First Posted: August 24, 2006
• Results First Posted: December 10, 2015
• Last Update Posted: December 10, 2015
• Last Verified: November 2015

Keywords provided by Eisai Inc.:

Refractory; Partial; Seizures

Additional relevant MeSH terms:

Seizures; Nervous System Diseases; Neurologic Manifestations