Refractory Partial Seizures
Conditions
Keywords
Seizures, epilepsy
Brief summary
The purpose of this study is to explore the maximum tolerated dose of E2007 in Japanese patients with refractory partial seizures which are uncontrolled with other anti-epileptic drugs (AEDs). Thirty patients will receive E2007 (dose escalating to the maximum of 12 mg per day). The dose of E2007 will be adjusted during 6 weeks. Subsequently, the dose will be fixed and maintained during 4 weeks.
Interventions
DRUGE2007
The dose of E2007 will start from 2 mg and will be increased by 2 mg every week up to 12 mg (the maximum dose). The dose will be adjusted during 6 weeks (i.e., titration period). Subsequently, the dose will be fixed and maintained during 4 weeks (Maintenance period). Patients must visit study site at Weeks -4, 1, 2, 3, 4, 5, 6, 8, 10 and 14 to confirm.
Sponsors
Eisai Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female aged between 20 and 64 years old. 2. Patients diagnosed with partial seizure (including secondarily generalized seizure). 3. Patients who have at least 3 counts of partial seizures during the previous 4 weeks prior to observation start and no seizure-free for 21 days during 8 weeks before the treatment start based on medical records. Simple partial seizure without motor signs will not be counted. 4. Patients who have been treated for at least 12 weeks but confirmed to be uncontrolled with more than one standard AED for 2 years. 5. Patients treated with stable doses of up to three AEDs. Only one cytochrome P450 (CYP) 3A4 inducer shown below will be allowed for concomitant use: * Carbamazepine * Phenytoin * Phenobarbital * Primidone 6. Patients on stable dose of anti-depressants, anti-anxiety drugs, or mood stabilizers from before 8 weeks.
Exclusion criteria
1. Patients with present or a history of Lennox-Gastaut syndrome. 2. Patients with present generalized seizures (e.g., absence, myoclonic). 3. Patients with a history of status epilepticus within 1 year. 4. Patients with seizure clusters where individual seizure cannot be counted within 8 weeks. 5. Patients with a history of psychogenic seizure. 6. Patients who underwent surgical operation for epilepsy within 2 years. 7. Patients using rescue benzodiazepines at least twice in a 4-week duration within 8 weeks (if 1 or 2 doses over 24-hour period considered one-time rescue). 8. Patients whose alanine aminotransferase (ALT) or aspartate aminotransferase (AST) at enrollment in observation period exceeds 1.5-fold the upper limit of normal (ULN), but those whose ALT or AST are constantly higher than ULN, they can enroll if ALT or AST remain in 3-fold the ULN. 9. Patients with significant active hematological disease; white blood cell (WBC) count \</=2500/uL or neutrophil count \</=1000 uL. 10. Patients on anti-psychotics or who have psychotic disorder and/or psychotic disorder(s) or unstable recurrent affective disorder(s) with a history of suicidal attempt within 2 years. 11. Patients who operate heavy equipment or drive should not be recruited into the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) | 10 weeks (Titration and Maintenance Periods) | MTD was defined by participants. For participants who completed treatment, MTD was dose at last administration. For subjects who discontinued due to adverse event (AE), the MTD depended on the number of days within down-titration. If these criteria were not applied, the MTD was determined based on suggestions from the Tolerability and Safety Evaluation Committee. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Total Seizure Frequency Per 28 Days From Baseline (Maintenance Period) ; LOCF | Baseline (Day -28 to Day 0), Week 1 to Week 10 | The percent change in seizure frequency per 28 days during the maintenance period was collected via patient diary cards. This was calculated using the last observation carried forward (LOCF) method. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Perampanel Orally administered E2007 (2, 4, 6, 8, 10, and 12 mg) once daily before bedtime (in fed administration insofar as possible). The dose started from 2 mg and up-titrated weekly in 2 mg increments up to the maximum 12 mg unless subjects met the following judgment on dose titration: 1.) If meeting titration limiting criteria, 2.) If subjects refused up-titration due to AEs, 3.) If the investigator judged it difficult to up-titrate due to AEs, or 4.) If treatment duration was less than 5 days. Total duration of treatment was 10 weeks from the initial dose. | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Miscellaneous | 1 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Perampanel |
|---|---|
| Age Continuous | 35.4 Years STANDARD_DEVIATION 10.6 |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 27 / 30 |
| serious Total, serious adverse events | 0 / 30 |
Outcome results
Primary
Maximum Tolerated Dose (MTD)
MTD was defined by participants. For participants who completed treatment, MTD was dose at last administration. For subjects who discontinued due to adverse event (AE), the MTD depended on the number of days within down-titration. If these criteria were not applied, the MTD was determined based on suggestions from the Tolerability and Safety Evaluation Committee.
Time frame: 10 weeks (Titration and Maintenance Periods)
Population: Safety analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Perampanel | Maximum Tolerated Dose (MTD) | 0 mg | 0 Participants |
| Perampanel | Maximum Tolerated Dose (MTD) | 2 mg | 2 Participants |
| Perampanel | Maximum Tolerated Dose (MTD) | 4 mg | 1 Participants |
| Perampanel | Maximum Tolerated Dose (MTD) | 6 mg | 6 Participants |
| Perampanel | Maximum Tolerated Dose (MTD) | 8 mg | 6 Participants |
| Perampanel | Maximum Tolerated Dose (MTD) | 10 mg | 5 Participants |
| Perampanel | Maximum Tolerated Dose (MTD) | 12 mg | 10 Participants |
Secondary
Percent Change in Total Seizure Frequency Per 28 Days From Baseline (Maintenance Period) ; LOCF
The percent change in seizure frequency per 28 days during the maintenance period was collected via patient diary cards. This was calculated using the last observation carried forward (LOCF) method.
Time frame: Baseline (Day -28 to Day 0), Week 1 to Week 10
Population: Efficacy analysis set:~Population after excluding : (a) Patients who do not meet the inclusion criteria, (b) Patients who meet the exclusion criteria which affect efficacy evaluation of E2007, (c) Patients untreated,(d) Patients with no evaluable data on efficacy,(e) Patients with \<80% treatment compliance
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Perampanel | Percent Change in Total Seizure Frequency Per 28 Days From Baseline (Maintenance Period) ; LOCF | -35 Percent change |