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

Epilepsy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00368472
• Other study ID #: E2007-A001-207
• Status: Completed
• Phase: Phase 2
• First received: August 22, 2006
• Last updated: November 5, 2015
• Start date: October 2006
• Est. completion date: July 2014

Study information

• Verified date: November 2015
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: European Union: European Medicines AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 138
• Est. completion date: July 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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 Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Epilepsy

Intervention

Drug:
• Perampanel
Perampanel 2 mg to 12 mg, once daily during the OLE study

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Czech Republic,  Estonia,  Finland,  France,  Germany,  Latvia,  Lithuania,  Netherlands,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	No
Secondary	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	No