Back to resultsA Long-term Extension Study of E2007 in Patients With Refractory Partial Seizures Uncontrolled With Other Anti-Epileptic Drugs (AEDs)
Primary Purpose
Refractory Partial Seizures
Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
perampanel
Sponsored by
About this trial
This is an interventional treatment trial for Refractory Partial Seizures focused on measuring Seizure, epilepsy
Eligibility Criteria
Inclusion criteria:
- Patients who consent to the study entry on their free will before starting any trial-related activities.
- Patients who participated in Study 231 and completed the required evaluation period (10 weeks).
- Patients who are certainly and voluntarily able to participate in this study and record their seizures by themselves or have family members or caregivers (or nurses, if hospitalized) record the seizures. Patients who wish to continue perampanel treatment and necessitate receiving the long- term administration judged by the investigator or sub-investigator.
Exclusion criteria:
- Pregnant or lactating women, women of child-bearing potential, women willing to become pregnant.
- Patients who are ineligible judged by the investigator or sub investigator in light of medical history or complication at enrollment in treatment period.
- Patients who operate heavy equipment or drive should not be recruited into the study.
- Patients who are ineligible for study entry judged by the investigator or sub-investigator.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Perampanel
Arm Description
Participants were treated with the perampanel dose that was administered in maintenance period of Study E2007-J081-231 (Study 231) [NCT00849212]. In some instances, a 1-step down-titration from the viewpoint of safety and up-titration to the maintenance dose of Study 231 was allowed. In general, 1 to 6 tablets of perampanel was administered orally as a 2-milligram (mg) tablet (2 mg to 12 mg) once daily before bedtime (under fed conditions as much as possible). The investigator, or subinvestigator, was allowed to complete the treatment by tapering the study drug after end of treatment or discontinuation (Follow-up Period), as appropriate. The taper period was 4 weeks at the longest.
Outcomes
Primary Outcome Measures
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Perampanel
Safety was assessed by monitoring adverse events (AEs), adverse drug reactions, clinical laboratory parameters, vital signs, 12-lead electrocardiogram, and dependency questionnaire. AEs were graded on a 3-point scale; 1) mild: (Grade 1) discomfort noticed, but no disruption of normal daily activity, 2) moderate: (Grade 2) discomfort reduced or affected normal daily activity, and 3) severe: (Grade 3) incapacitating, with inability to work or to perform normal daily activity. AE severity associated with abnormal changes in laboratory parameters was assessed using the Ministry of Health and Welfare Notification Number 80 "Classification of Severity of Adverse Drug Reactions of Medicinal Products". TEAEs were defined as AEs that emerged during treatment (absent at pretreatment [Baseline]), reemerged during treatment (were present at pretreatment but stopped before treatment), or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous.
Secondary Outcome Measures
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316
Seizure frequency was derived from information (seizure count and type) recorded in the participant diary. The seizure frequency per 28 days was calculated as the number of seizures over the time interval multiplied by 28 and divided by the number of days in the interval. The percent change in 28-day seizure frequency from baseline was assessed for overall seizures, overall partial seizures, overall generalized seizures, and unclassified seizures. Of the 21 participants, 20 participants concomitantly used at least 1 inducer anti-epileptic drug (AED) (carbamazepine, phenytoin, phenobarbital, or primidone), and 1 participant used only non-inducer AEDs. The data is presented as median percent change with full range.
Responder Rate During the Treatment Period-LOCF
Responder rate (percentage of participants with greater than or equal to 50% reduction in seizure frequency for 28 days in the Treatment Period relative to that for 28 days in the observation period of Study 231 [responder]. If the reduction in seizure frequency is less than 50%, then the participants are considered as non-responders.
LOCF = Last Observation Carried Forward.
The Patient Global Impression of Change (PGIC) at Week 52 and End of Treatment
Each participant evaluated him/herself for PGIC at Week 52 of the Treatment Period and at the end of treatment (or discontinuation) by comparing seizure conditions during 4 weeks before Week 52 of the Treatment Period and those during 4 weeks before end of treatment (or discontinuation) of the open label extension study with those during 4 weeks before start of the Treatment Period of Study 231. Assessment was implemented based on frequency of seizure, severity of seizures, AEs, and overall conditions using the 7-grade scores. The evaluation used a 7-point scale with the scores 1: Very much improved, 2: Much improved, 3: Minimally improved, 4: No change, 5: Minimally worse, 6: Much worse, 7: Very much worse.
The Clinical Global Impression of Change (CGIC) at Week 52 and End of Treatment
The investigator evaluated each participant for CGIC at Week 52 of the Treatment Period and at the end of treatment (or discontinuation) by comparing medical conditions during 4 weeks before Week 52 of the Treatment Period and those during 4 weeks before end of treatment (or discontinuation) of the open label extension study with those during 4 weeks before start of the Treatment Period of Study 231. Assessment was implemented based on frequency of seizure, severity of seizures, AEs, and overall conditions using the 7-grade scores. The evaluation used a 7-point scale with the scores 1: Very much improved, 2: Much improved, 3: Minimally improved, 4: No change, 5: Minimally worse, 6: Much worse, 7: Very much worse.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00903786
Brief Title
A Long-term Extension Study of E2007 in Patients With Refractory Partial Seizures Uncontrolled With Other Anti-Epileptic Drugs (AEDs)
Official Title
A Long-term Extension Study of E2007 in Patients With Refractory Partial Seizures Uncontrolled With Other Anti-Epileptic Drugs (AEDs)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
June 17, 2009 (Actual)
Primary Completion Date
August 8, 2016 (Actual)
Study Completion Date
October 31, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eisai Co., Ltd.
4. Oversight
5. Study Description
Brief Summary
The purpose of this trial is to investigate the safety and tolerability of perampanel in long- term treatment in the patients with refractory partial epilepsy (uncontrolled with other anti-epileptic drugs) who completed Week 10 of Phase II Study E2007-J081-231 study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory Partial Seizures
Keywords
Seizure, epilepsy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Perampanel
Arm Type
Experimental
Arm Description
Participants were treated with the perampanel dose that was administered in maintenance period of Study E2007-J081-231 (Study 231) [NCT00849212]. In some instances, a 1-step down-titration from the viewpoint of safety and up-titration to the maintenance dose of Study 231 was allowed. In general, 1 to 6 tablets of perampanel was administered orally as a 2-milligram (mg) tablet (2 mg to 12 mg) once daily before bedtime (under fed conditions as much as possible).
The investigator, or subinvestigator, was allowed to complete the treatment by tapering the study drug after end of treatment or discontinuation (Follow-up Period), as appropriate. The taper period was 4 weeks at the longest.
Intervention Type
Drug
Intervention Name(s)
perampanel
Other Intervention Name(s)
E2007, Fycompa
Intervention Description
Patients will receive the same oral dosage (2 mg up to 12 mg once daily before bedtime) as used in the maintenance period of Study 231.
Primary Outcome Measure Information:
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Perampanel
Description
Safety was assessed by monitoring adverse events (AEs), adverse drug reactions, clinical laboratory parameters, vital signs, 12-lead electrocardiogram, and dependency questionnaire. AEs were graded on a 3-point scale; 1) mild: (Grade 1) discomfort noticed, but no disruption of normal daily activity, 2) moderate: (Grade 2) discomfort reduced or affected normal daily activity, and 3) severe: (Grade 3) incapacitating, with inability to work or to perform normal daily activity. AE severity associated with abnormal changes in laboratory parameters was assessed using the Ministry of Health and Welfare Notification Number 80 "Classification of Severity of Adverse Drug Reactions of Medicinal Products". TEAEs were defined as AEs that emerged during treatment (absent at pretreatment [Baseline]), reemerged during treatment (were present at pretreatment but stopped before treatment), or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous.
Time Frame
From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months
Secondary Outcome Measure Information:
Title
Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316
Description
Seizure frequency was derived from information (seizure count and type) recorded in the participant diary. The seizure frequency per 28 days was calculated as the number of seizures over the time interval multiplied by 28 and divided by the number of days in the interval. The percent change in 28-day seizure frequency from baseline was assessed for overall seizures, overall partial seizures, overall generalized seizures, and unclassified seizures. Of the 21 participants, 20 participants concomitantly used at least 1 inducer anti-epileptic drug (AED) (carbamazepine, phenytoin, phenobarbital, or primidone), and 1 participant used only non-inducer AEDs. The data is presented as median percent change with full range.
Time Frame
From Week 1 through Week 316 and Follow-up Period of the Extension Study, up to approximately 7 years 2 months
Title
Responder Rate During the Treatment Period-LOCF
Description
Responder rate (percentage of participants with greater than or equal to 50% reduction in seizure frequency for 28 days in the Treatment Period relative to that for 28 days in the observation period of Study 231 [responder]. If the reduction in seizure frequency is less than 50%, then the participants are considered as non-responders.
LOCF = Last Observation Carried Forward.
Time Frame
Week 1 through Week 316 and Follow-up period of the Extension study, up to approximately 7 years 2 months
Title
The Patient Global Impression of Change (PGIC) at Week 52 and End of Treatment
Description
Each participant evaluated him/herself for PGIC at Week 52 of the Treatment Period and at the end of treatment (or discontinuation) by comparing seizure conditions during 4 weeks before Week 52 of the Treatment Period and those during 4 weeks before end of treatment (or discontinuation) of the open label extension study with those during 4 weeks before start of the Treatment Period of Study 231. Assessment was implemented based on frequency of seizure, severity of seizures, AEs, and overall conditions using the 7-grade scores. The evaluation used a 7-point scale with the scores 1: Very much improved, 2: Much improved, 3: Minimally improved, 4: No change, 5: Minimally worse, 6: Much worse, 7: Very much worse.
Time Frame
Week 52 and End of Treatment; up to approximately 7 years 2 months
Title
The Clinical Global Impression of Change (CGIC) at Week 52 and End of Treatment
Description
The investigator evaluated each participant for CGIC at Week 52 of the Treatment Period and at the end of treatment (or discontinuation) by comparing medical conditions during 4 weeks before Week 52 of the Treatment Period and those during 4 weeks before end of treatment (or discontinuation) of the open label extension study with those during 4 weeks before start of the Treatment Period of Study 231. Assessment was implemented based on frequency of seizure, severity of seizures, AEs, and overall conditions using the 7-grade scores. The evaluation used a 7-point scale with the scores 1: Very much improved, 2: Much improved, 3: Minimally improved, 4: No change, 5: Minimally worse, 6: Much worse, 7: Very much worse.
Time Frame
Week 52 and End of Treatment, up to approximately 7 years 2 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Patients who consent to the study entry on their free will before starting any trial-related activities.
Patients who participated in Study 231 and completed the required evaluation period (10 weeks).
Patients who are certainly and voluntarily able to participate in this study and record their seizures by themselves or have family members or caregivers (or nurses, if hospitalized) record the seizures. Patients who wish to continue perampanel treatment and necessitate receiving the long- term administration judged by the investigator or sub-investigator.
Exclusion criteria:
Pregnant or lactating women, women of child-bearing potential, women willing to become pregnant.
Patients who are ineligible judged by the investigator or sub investigator in light of medical history or complication at enrollment in treatment period.
Patients who operate heavy equipment or drive should not be recruited into the study.
Patients who are ineligible for study entry judged by the investigator or sub-investigator.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kazunori Saeki
Organizational Affiliation
Neuroscience Clinical Development Section. JAC PCU. Eisai Co., Ltd.
Official's Role
Study Director
Facility Information:
City
Kitakyusyu
State/Province
Fukuoka
Country
Japan
City
Kobe
State/Province
Hyogo
Country
Japan
City
Sendai
State/Province
Miyagi
Country
Japan
City
Komatsushima
State/Province
Tokushima
Country
Japan
City
Kodaira
State/Province
Tokyo
Country
Japan
City
Kyoto
Country
Japan
City
Nagasaki
Country
Japan
City
Niigata
Country
Japan
City
Shizuoka
Country
Japan
12. IPD Sharing Statement
Learn more about this trial
A Long-term Extension Study of E2007 in Patients With Refractory Partial Seizures Uncontrolled With Other Anti-Epileptic Drugs (AEDs)
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