Refractory Partial Onset Seizures
Conditions
Keywords
Refractory Partial Onset Seizures, epilepsy
Brief summary
This was an open-label extension study in adolescent and adult (between 12 and 80 years old) participants who had completed their participation in Study E2080-A001-301. The main objective of this study was to evaluate the safety and efficacy of long-term administration of rufinamide for the control of epileptic seizures in participants who had refractory partial seizures despite treatment with a maximum of three approved antiepileptic drugs (AEDs).
Interventions
DRUGRufinamide
Dose will be maintained within the range of 2400 to 4800 mg/day (i.e., 1200 to 2400 mg twice daily).
Sponsors
Eisai Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Completion of Study E2080-A001-301 and full compliance with the inclusion and
Exclusion criteria
for that study (excluding criteria that are related to seizure occurrences). 2. Patient willing to participate and written consent signed by patient or legal guardian provided prior to entering this study or undergoing any study procedures. In addition, if the patient is unable to provide written informed consent and it is provided by a legal guardian, assent of the patient (if the patient is able) must also be obtained. 3. Female patients of non-childbearing potential by reason of surgery, radiation, or menopause (at least one year post onset); female patients of childbearing potential who are using at least two approved methods of contraception (such as an intrauterine device \[IUD\], implant, oral contraceptive, or barrier method plus spermicide). Use of a low-dose estrogen oral contraceptive alone will not be permitted. Female patients of childbearing potential must agree to continue to use two approved methods of contraception through the follow-up visit or for 30 days after their final dose of study medication, whichever is longer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in Total Partial Seizure Frequency Per 28 Days Relative to the Baseline Phase | Baseline, Titration Phase (Days 1 to 18), Maintenance Phase | Seizure data was collected via patient diaries. OL refers to open-label. |
Countries
United States
Participant flow
Recruitment details
Participants who completed double-blind study E2080-A001-301 were allowed to enter in open-label extension Study 302. Participants completed a 12-day Transition Phase in Study 301 and received the same rufinamide maintenance dose that they achieved in Study 301 (Arm1), or transitioned from placebo to 3200 mg/day, beginning at 800 mg/day (Arm2).
Pre-assignment details
Four participants who intended to enroll from Study 301 to 302 did not enroll and were considered screening failures.
Participants by arm
| Arm | Count |
|---|---|
| Rufinamide (Rufinamide During Core Study) Participants entered this open-label extension study from E2080-A001-301 double-blind core study, where they received rufinamide in the core study. Prior to starting the extension study, participants completed a 12-day Transition Phase. For participants who immediately entered study 302 after study 301, rufinamide was maintained at dose of 2400 or 3200 mg/day achieved at the end of study 301. Participants with delay between the end of Study 301 and the beginning of Study 302 started rufinamide at a dose of 800 mg/day, and had the dose titrated to the maximum tolerated dose (2400 or 3200 mg/day) over the next 12 to 18 days. During the open-ended open-label Maintenance Phase, changes in the rufinamide dose were permitted for all participants; however, the dose was maintained within the range of 2400 to 4800 mg/day (i.e., 1200 to 2400 mg twice daily). | 134 |
| Rufinamide (Placebo During Core Study) Participants entered this open-label extension study from E2080-A001-301 double-blind core study, where they received placebo in the core study. Prior to starting the extension study, participants completed a 12-day Transition Phase where they transitioned from placebo to rufinamide at 800 mg/day at the start of transition phase, with subsequent dose increased to 3200 mg/day. During the open-ended open-label Maintenance Phase, changes in the rufinamide dose were permitted for all participants; however, the dose was maintained within the range of 2400 to 4800 mg/day (i.e., 1200 to 2400 mg twice daily). | 152 |
| Total | 286 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 9 | 26 |
| Overall Study | Change of meds | 2 | 3 |
| Overall Study | Diary non-compliance | 1 | 0 |
| Overall Study | Lack of Efficacy | 27 | 40 |
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Medication non-compliance | 4 | 1 |
| Overall Study | Miscellaneous | 2 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Request of the investigator or sponsor | 67 | 54 |
| Overall Study | Withdrawal by Subject | 20 | 24 |
Baseline characteristics
| Characteristic | Rufinamide (Rufinamide During Core Study) | Rufinamide (Placebo During Core Study) | Total |
|---|---|---|---|
| Age, Customized 12 to <18 years | 6 participants | 18 participants | 24 participants |
| Age, Customized 18 to <65 years | 123 participants | 129 participants | 252 participants |
| Age, Customized >=65 years | 5 participants | 5 participants | 10 participants |
| Race/Ethnicity, Customized Asian/Pacific Islander | 2 participants | 2 participants | 4 participants |
| Race/Ethnicity, Customized Black | 7 participants | 13 participants | 20 participants |
| Race/Ethnicity, Customized Hispanic | 10 participants | 11 participants | 21 participants |
| Race/Ethnicity, Customized Native American | 0 participants | 2 participants | 2 participants |
| Race/Ethnicity, Customized Other | 0 participants | 3 participants | 3 participants |
| Race/Ethnicity, Customized White | 115 participants | 121 participants | 236 participants |
| Sex: Female, Male Female | 63 Participants | 80 Participants | 143 Participants |
| Sex: Female, Male Male | 71 Participants | 72 Participants | 143 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 134 | 0 / 152 |
| other Total, other adverse events | 88 / 134 | 114 / 152 |
| serious Total, serious adverse events | 29 / 134 | 23 / 152 |
Outcome results
Primary
Percentage Change in Total Partial Seizure Frequency Per 28 Days Relative to the Baseline Phase
Seizure data was collected via patient diaries. OL refers to open-label.
Time frame: Baseline, Titration Phase (Days 1 to 18), Maintenance Phase
Population: Intent-to-treat (ITT) population: All subjects who completed titration to open-label medication
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Rufinamide (Rufinamide During Core Study) | Percentage Change in Total Partial Seizure Frequency Per 28 Days Relative to the Baseline Phase | OL Titration Phase | -35.65 Percentage change |
| Rufinamide (Rufinamide During Core Study) | Percentage Change in Total Partial Seizure Frequency Per 28 Days Relative to the Baseline Phase | OL Maintenance Phase | -30.95 Percentage change |
| Rufinamide (Placebo During Core Study) | Percentage Change in Total Partial Seizure Frequency Per 28 Days Relative to the Baseline Phase | OL Titration Phase | -45.10 Percentage change |
| Rufinamide (Placebo During Core Study) | Percentage Change in Total Partial Seizure Frequency Per 28 Days Relative to the Baseline Phase | OL Maintenance Phase | -31.10 Percentage change |