Evaluation of the Efficacy and Safety of E2007 (Perampanel) Given as Adjunctive Therapy in Subjects With Refractory Partial Seizures

Epilepsy Clinical Trial

Official title:

An Open-Label Extension Phase of the Double-Blind, Placebo-Controlled, Dose-Escalation, Parallel-Group Studies to Evaluate the Efficacy and Safety of E2007 (Perampanel) Given as Adjunctive Therapy in Subjects With Refractory Partial Seizures

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00735397
• Other study ID #: E2007-G000-307
• Status: Completed
• Phase: Phase 3
• First received: August 13, 2008
• Last updated: February 11, 2016
• Start date: October 2008
• Est. completion date: September 2014

Study information

• Verified date: February 2016
• 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 was to evaluate the safety and tolerability of perampanel (up to 12 mg/day) given as adjunctive treatment in subjects with refractory partial seizures and to evaluate the maintenance of effect of perampanel for the control of refractory partial seizures.

Description:

This was an open-label extension (OLE) study for subjects who completed one of the following double-blind, placebo-controlled, Phase 3 studies: E2007-G000-304 (NCT00699972), E2007-G000-305 (NCT00699582), and E2007-G000-306 (NCT00700310). This OLE study consisted of 2 phases: an Open-label Treatment Phase (comprised of a 16-week blinded Conversion Period and a 256-week Maintenance Period) and a Follow-up Phase (4 weeks). During the Conversion Period, subjects and investigators remained blinded to the treatment received in the previous DB study. To achieve this, all subjects continued to take 6 tablets of study medication (2 mg perampanel or matching placebo) or fewer as they were instructed during the core Double-Blind (DB) study. During the open-label Maintenance Period, subjects were treated with the perampanel dose that provided the best combination of individual efficacy and tolerability.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1218
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

Each participant who met the following criteria were enrolled in this study:

1. Who completed Visit 8 of study E2007-G000-304, E2007-G000-305, or E2007-G000-306 and complied with the inclusion and exclusion criteria for that study (excluding criteria that are related to seizure occurrences).

2. Provided written informed consent signed by participant or legal guardian prior to entering the study or undergoing any study procedures (If the written informed consent was provided by the legal guardian because the participant was unable to do so, a written or verbal assent from the participant was obtained).

3. Who was considered reliable and willing to be available for the study period and record seizures and report adverse events them self or have a caregiver who can record and report the events for them.

4. Females who were either of non-childbearing potential (defined as having undergone surgical sterilization, or postmenopausal [>age 50 and amenorrheic for 12 months]) or of childbearing potential. Females of childbearing potential were enrolled only if they agreed to be abstinent or continue using at least 1 medically acceptable method of contraception (eg, a double-barrier method [eg, condom + spermicide, condom + diaphragm with spermicide], IUD, or have a vasectomised partner) throughout the study period and for 2 months after the last dose of study drug. Women using hormonal contraceptives were required to use an additional approved method of contraception (as described previously) continuously throughout the entire study period and for 2 months after the last dose of study drug. (It was not required for male subjects to use contraceptive measures based on preclinical toxicology data).

5. Continued to be treated with a stable dose of 1 or a maximum of 3 approved anti-epileptic drugs.

Exclusion Criteria:

Participants who met the following criteria were excluded from the study:

1. Those who, for any reason, discontinued early from the preceding double-blind study.

Study Design

Endpoint Classification: Safety 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 in the Open-Label Extension (OLE) study up to approximately 5 years

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Bulgaria,  Canada,  Chile,  China,  Czech Republic,  Estonia,  Finland,  France,  Germany,  Greece,  Hong Kong,  Hungary,  India,  Israel,  Italy,  Korea, Republic of,  Latvia,  Lithuania,  Malaysia,  Mexico,  Netherlands,  Philippines,  Poland,  Portugal,  Romania,  Russian Federation,  Serbia,  South Africa,  Spain,  Sweden,  Taiwan,  Thailand,  Ukraine,  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 with 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.	From date of first dose of perampanel up to 30 days after the last dose of perampanel or up to approximately 5 years.	Yes
Secondary	Median 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 pre-perampanel baseline was assessed for all partial-onset seizure types. The pre-perampanel baseline was defined as: (1) for participants who had been assigned to placebo treatment in the core DB study, the pre-perampanel baseline was computed from all data during the core DB study, and (2) for participants who had been assigned to perampanel in the core DB study, the pre-perampanel baseline was computed from the pre-randomization phase of the core DB study.	Pre-perampanel Baseline and Weeks (1-13, 14-26, 27-39, 40-52, 53-65, 66-78, 79-91, 92-104, 105-117, 118-130, 131-143, 144-156, 157-169, 170-182, 183-195, 196-208, 209-221, 222-234, 235-247, and 248-260)	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. The pre-perampanel baseline was defined as: (1) for participants who had been assigned to placebo treatment in the core DB study, the Pre-perampanel baseline was computed from all data during the core Double-Blind (DB) study, and (2) for participants who had been assigned to perampanel in the core DB study, the pre-perampanel baseline was computed from the pre-randomization phase of the core DB study. The data is presented as percent responders.	Pre-perampanel Baseline and Weeks (1-13, 14-26, 27-39, 40-52, 53-65, 66-78, 79-91, 92-104, 105-117, 118-130, 131-143, 144-156, 157-169, 170-182, 183-195, 196-208, 209-221, 222-234, 235-247, 248-260)	No