Epilepsy
Conditions
Keywords
Refractory, Partial, Seizures
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.
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.
Interventions
DRUGPerampanel
Perampanel 2 mg to 12 mg, once daily during the OLE study
Sponsors
Eisai Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Non-serious Adverse Events (AEs) and Treatment-emergent Serious Adverse Events (SAEs) | 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
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Seizure Frequency Per 28 Days Relative to Pre-Perampanel Baseline | 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. |
| Percentage of Participants Who Experienced a 50% or Greater Reduction in Seizure Frequency Per 28 Days Relative to the Pre-perampanel Baseline | 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. |
Countries
Australia, Belgium, Czechia, Estonia, Finland, France, Germany, Latvia, Lithuania, Netherlands, Spain, Sweden, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Perampanel Participants previously receiving perampanel/placebo in the double-blind study, were titrated to receive perampanel 2 mg to 12 mg, once daily in the Open-Label Extension (OLE) study. | 138 |
| Total | 138 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 22 |
| Overall Study | Diary non-compliance | 1 |
| Overall Study | Medication non-compliance | 4 |
| Overall Study | Missing Final Disposition Date | 1 |
| Overall Study | Other | 32 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Request of Investigator or Sponsor | 3 |
| Overall Study | Withdrawal by Subject | 40 |
Baseline characteristics
| Characteristic | Perampanel |
|---|---|
| Age, Continuous | 40.7 Years STANDARD_DEVIATION 11.87 |
| Sex: Female, Male Female | 80 Participants |
| Sex: Female, Male Male | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 112 / 138 |
| serious Total, serious adverse events | 33 / 138 |
Outcome results
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.
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
Population: Safety Analysis Set was defined as participants who received at least 1 dose of open-label perampanel and had at least 1 safety assessment after the first dose of perampanel in the OLE study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Perampanel | Number of Participants With Treatment-emergent Non-serious Adverse Events (AEs) and Treatment-emergent Serious Adverse Events (SAEs) | Treatment-emergent non-serious AEs | 112 Participants |
| Perampanel | Number of Participants With Treatment-emergent Non-serious Adverse Events (AEs) and Treatment-emergent Serious Adverse Events (SAEs) | Treatment-emergent SAEs | 33 Participants |
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.
Time frame: Baseline up to week 221
Population: The analysis was based on the Full Intent to Treat (ITT) Analysis Set, defined as participants who received at least 1 dose of open-label perampanel and had valid seizure data during the OLE study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Perampanel | Percentage of Participants Who Experienced a 50% or Greater Reduction in Seizure Frequency Per 28 Days Relative to the Pre-perampanel Baseline | 36.2 Percent responders |
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.
Time frame: Baseline up to Week 221
Population: The analysis was based on the Full Intent to Treat (ITT) Analysis Set, defined as participants who received at least 1 dose of open-label perampanel and had valid seizure data during the OLE study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Perampanel | Percent Change in Seizure Frequency Per 28 Days Relative to Pre-Perampanel Baseline | -31.5 Percent Change |