Lennox-Gastaut Syndrome
Conditions
Keywords
Epilepsy, Seizures
Brief summary
To investigate the safety of long term administration of E2080 in the patients with Lennox-Gastaut syndrome who completed the E2080-J081-304 Study.
Interventions
DRUGRufinamide
The target dosage is approximately 45 mg/kg/day, taken orally twice a day.
Sponsors
Eisai Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to 30 Years
Healthy volunteers
No
Inclusion criteria
1. Participants who have completed the evaluation of Week 12 of the E2080-J081-304 study. 2. Male participants with reproductive ability and female participants with child-bearing potential, or their partners, had to be able to take medically appropriate contraceptive measures. 3. Participants who have provided a written informed consent to participate in this clinical trial until the evaluation of week 12 of the E2080-J081-304 study. 4. Participants who had a family member or a caregiver capable of recording the reporting diary, providing participant information necessary for the study, assisting treatment compliance, and accompanying the participant on scheduled visit days during the study period.
Exclusion criteria
1. Participants who were judged by the investigator that they are unfit to participate in this clinical study for safety reasons based on the information up to the evaluation of week 12 of the E2080-J081-304 Study. 2. Participants who were judged by the investigator that they are likely to become non-compliant with administration during the clinical trial period. 3. Participants who were judged by the investigator that they were unfit to participate in this clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Rufinamide | From date of first dose up to 30 days after the last dose of study treatment, up to approximately 2 years 10 months | Safety was assessed by monitoring and recording all adverse events (AEs), serious adverse events (SAEs), clinical laboratory tests, blood pressure, pulse rate, physical examination, and 12-lead electrocardiogram (ECG). Treatment-emergent adverse events (TEAEs) were defined as AEs that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug and increased in National Cancer Institute Common Toxicity Criteria (NCI CTC version 3.0) grade during the study or 30 days after discontinuation from the study. AEs were considered serious if it resulted in; death, was life-threatening, hospitalization/prolonged hospitalization, persistent or significant disability/incapacity, or a congenital anomaly/birth defect. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Tonic-Atonic Seizure Frequency From Baseline (Per 28 Days) | Baseline (Observation period in Study 304), Week 12, Week 24, Week 32, Week 40, Week 52 and Week 52 LOCF | The sum of the frequencies of tonic seizures and atonic seizures was defined as the tonic-atonic seizure frequency. The percent change in tonic-atonic seizure frequency was calculated using the tonic-atonic seizure frequency per 28 days of the Observation Period in Study 304 as the baseline and the tonic-atonic seizure frequency at Weeks 12, 24, 32, 40, 52 and Week 52 Last Observation Carried Forward (LOCF) as the post-treatment value. Percentage change in tonic - atonic seizure frequency was calculated as follows: \[100 x (post-treatment value - baseline)/ baseline\]. The frequency of epileptic seizures was recorded in the seizure diary by the recorder. Seizure frequency was counted based on the classification established by the International League Against Epilepsy (ILAE). The diary recorder monitored the participant and recorded the seizure diary in a consistent manner, and continued these practices throughout the study period. |
| Percent Change in the Total Seizure Frequency From Baseline (Per 28 Days) | Baseline (Observation period in Study 304), Week 12, Week 24, Week 32, Week 40, Week 52 and Week 52 LOCF | Percent change in the total seizure frequency (per 28 days) was calculated using the total seizure frequency per 28 days of the Observation Period of Study 304 as the baseline and the total seizure frequency per 28 days at Weeks 12, 24, 32, 40, 52 and Week 52 LOCF as the post-treatment value. Percentage change in total seizure frequency was calculated as follows: \[100 x (post-treatment value - baseline)/ baseline\]. |
| Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Baseline (Observation period in Study 304), Week 12, Week 24, Week 32, Week 40, Week 52 and Week 52 LOCF | Percent change in the frequency of seizures other than tonic-atonic seizures (per 28 days) was calculated using the total seizure frequency per 28 days of the Observation Period as the baseline and the total seizure frequency per 28 days of the Weeks, 12, 24, 32, 40, 52 and 52 LOCF as the post-treatment value. Percentage change in total seizure frequency was calculated as follows: \[100 x (post-treatment value - baseline)/ baseline\]. Seizures analyzed other than tonic-atonic seizures included: Partial seizure frequency, Absence seizure, Atypical absence seizure, Myoclonic seizure, Tonic seizure, Tonic-clonic seizure, Atonic seizure, and Unclassified epileptic seizure. This data was based on the diary data collected for 7 days after each visit. Seizure frequency was counted based on the classification established by the ILAE. The diary recorder monitored the participant and recorded the seizure diary in a consistent manner. |
| Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 12, Week 24, Week 32, Week 40, Week 52 and Week 52 LOCF | Categorized percent change in Tonic-atonic seizure frequency per 28 Days by visit relative to the baseline (Observation Phase in Study 304) was determined based on the diary data collected for 7 days after each visit. The Efficacy Analysis Set was used. |
| Percentage of Participants With An Increase In Tonic-Atonic Seizure Frequency | Week 12, Week 24, Week 32, Week 40, Week 52 and Week 52 LOCF | Number of participants with an increase in Tonic-atonic seizure frequency per 28 Days by visit relative to the baseline (Observation Phase in Study 304) was determined based on the diary data collected for 7 days after each visit. The Efficacy Analysis Set was used. |
Countries
Japan
Participant flow
Pre-assignment details
Participants who successfully completed Study 304 were enrolled into this study.
Participants by arm
| Arm | Count |
|---|---|
| Rufinamide Ralfinamide was administered orally twice daily after breakfast and dinner. Participants on placebo in Study 304 were titrated over to rufinamide within 2 weeks during the Conversion Period. As a general rule, the dose of rufinamide at the end of the Conversion Period was maintained throughout the Maintenance Period. | 54 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse event, non-fatal | 4 |
| Overall Study | Other | 2 |
| Overall Study | Withdrawal by Subject | 7 |
Baseline characteristics
| Characteristic | Rufinamide |
|---|---|
| Age, Continuous | 15 Years STANDARD_DEVIATION 6.8 |
| Age, Customized ≥12 to <17 years | 11 Participants |
| Age, Customized ≥17 years | 21 Participants |
| Age, Customized ≥4 to <12 years | 22 Participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 54 |
| other Total, other adverse events | 54 / 54 |
| serious Total, serious adverse events | 9 / 54 |
Outcome results
Primary
Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Rufinamide
Safety was assessed by monitoring and recording all adverse events (AEs), serious adverse events (SAEs), clinical laboratory tests, blood pressure, pulse rate, physical examination, and 12-lead electrocardiogram (ECG). Treatment-emergent adverse events (TEAEs) were defined as AEs that started on or after the date and time of administration of first dose of test drug, but not later than 30 days after discontinuation from the study, or if the AE was present prior to the administration of the first dose of test drug and increased in National Cancer Institute Common Toxicity Criteria (NCI CTC version 3.0) grade during the study or 30 days after discontinuation from the study. AEs were considered serious if it resulted in; death, was life-threatening, hospitalization/prolonged hospitalization, persistent or significant disability/incapacity, or a congenital anomaly/birth defect.
Time frame: From date of first dose up to 30 days after the last dose of study treatment, up to approximately 2 years 10 months
Population: Safety analysis set included all treated participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rufinamide | Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Rufinamide | TEAEs | 54 Participants |
| Rufinamide | Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Rufinamide | Treatment-related TEAEs | 38 Participants |
| Rufinamide | Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Rufinamide | SAEs | 9 Participants |
| Rufinamide | Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Rufinamide | Treatment-related SAEs | 2 Participants |
| Rufinamide | Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Rufinamide | AEs leading to study drug withdrawal | 3 Participants |
| Rufinamide | Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Rufinamide | AEs leading to study drug dose reduction | 12 Participants |
Secondary
Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders)
Categorized percent change in Tonic-atonic seizure frequency per 28 Days by visit relative to the baseline (Observation Phase in Study 304) was determined based on the diary data collected for 7 days after each visit. The Efficacy Analysis Set was used.
Time frame: Week 12, Week 24, Week 32, Week 40, Week 52 and Week 52 LOCF
Population: Efficacy Analysis Set included all participants with evaluable efficacy data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 24 75% Reduction - No | 88.4 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 24 50% Reduction - Yes | 39.5 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 24 50% Reduction -No | 60.5 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 40 25% Reduction - No | 39 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 52 100% Reduction - Yes | 5 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 52 100% Reduction - No | 95 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 12 100% Reduction - Yes | 6.5 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 12 100% Reduction - No | 93.5 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 12 75% Reduction - Yes | 17.4 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 12 75% Reduction - No | 82.6 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 12 50% Reduction - Yes | 43.5 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 12 50% Reduction - No | 56.5 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 12 25% Reduction - Yes | 71.7 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 12 25% Reduction - No | 28.3 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 24 100% Reduction - Yes | 2.3 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 24 100% Reduction - No | 97.7 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 24 75% Reduction - Yes | 11.6 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 24 25% Reduction - Yes | 65.1 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 24 25% Reduction - No | 34.9 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 32 100% Reduction - Yes | 2.4 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 32 100% Reduction - No | 97.6 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 32 75% Reduction - Yes | 19 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 32 75% Reduction - No | 81 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 32 50% Reduction - Yes | 47.6 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 32 50% Reduction - No | 52.4 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 32 25% Reduction - Yes | 66.7 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 32 25% Reduction - No | 33.3 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 40 100% Reduction - Yes | 4.9 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 40 100% Reduction - No | 95.1 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 40 75% Reduction - Yes | 17.1 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 40 75% Reduction - No | 82.9 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 40 50% Reduction - Yes | 48.8 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 40 50% Reduction - No | 51.2 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 40 25% Reduction - Yes | 61 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 52 75% Reduction - Yes | 20 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 52 75% Reduction -No | 80 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 52 50% Reduction - Yes | 37.5 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 52 50% Reduction - No | 62.5 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 52 25% Reduction - Yes | 60 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 52 25% Reduction - No | 40 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 52 (LOCF) 100% Reduction - Yes | 8.7 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 52 (LOCF) 100% Reduction - No | 91.3 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 52 (LOCF) 75% Reduction - Yes | 21.7 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 52 (LOCF) 75% Reduction -No | 78.3 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 52 (LOCF) 50% Reduction - Yes | 39.1 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 52 (LOCF) 50% Reduction - No | 60.9 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 52 (LOCF) 25% Reduction - Yes | 63 Percentage of participants |
| Rufinamide | Percentage of Participants Who Achieved 100%, 75%, 50% or 25% Reduction in Tonic-Atonic Seizure Frequency (Responders) | Week 52 (LOCF) 25% Reduction - No | 37 Percentage of participants |
Secondary
Percentage of Participants With An Increase In Tonic-Atonic Seizure Frequency
Number of participants with an increase in Tonic-atonic seizure frequency per 28 Days by visit relative to the baseline (Observation Phase in Study 304) was determined based on the diary data collected for 7 days after each visit. The Efficacy Analysis Set was used.
Time frame: Week 12, Week 24, Week 32, Week 40, Week 52 and Week 52 LOCF
Population: Efficacy Analysis Set included all participants with evaluable efficacy data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rufinamide | Percentage of Participants With An Increase In Tonic-Atonic Seizure Frequency | Week 52 LOCF Increase - Yes | 19.6 Percentage of participants |
| Rufinamide | Percentage of Participants With An Increase In Tonic-Atonic Seizure Frequency | Week 52 LOCF Increase - No | 80.4 Percentage of participants |
| Rufinamide | Percentage of Participants With An Increase In Tonic-Atonic Seizure Frequency | Week 12 Increase - Yes | 21.7 Percentage of participants |
| Rufinamide | Percentage of Participants With An Increase In Tonic-Atonic Seizure Frequency | Week 12 Increase - No | 78.3 Percentage of participants |
| Rufinamide | Percentage of Participants With An Increase In Tonic-Atonic Seizure Frequency | Week 24 Increase - Yes | 23.3 Percentage of participants |
| Rufinamide | Percentage of Participants With An Increase In Tonic-Atonic Seizure Frequency | Week 24 Increase - No | 76.7 Percentage of participants |
| Rufinamide | Percentage of Participants With An Increase In Tonic-Atonic Seizure Frequency | Week 32 Increase - Yes | 16.7 Percentage of participants |
| Rufinamide | Percentage of Participants With An Increase In Tonic-Atonic Seizure Frequency | Week 32 Increase - No | 83.3 Percentage of participants |
| Rufinamide | Percentage of Participants With An Increase In Tonic-Atonic Seizure Frequency | Week 40 Increase - Yes | 9.8 Percentage of participants |
| Rufinamide | Percentage of Participants With An Increase In Tonic-Atonic Seizure Frequency | Week 40 Increase - No | 90.2 Percentage of participants |
| Rufinamide | Percentage of Participants With An Increase In Tonic-Atonic Seizure Frequency | Week 52 Increase - Yes | 22.5 Percentage of participants |
| Rufinamide | Percentage of Participants With An Increase In Tonic-Atonic Seizure Frequency | Week 52 Increase -No | 77.5 Percentage of participants |
Secondary
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Percent change in the frequency of seizures other than tonic-atonic seizures (per 28 days) was calculated using the total seizure frequency per 28 days of the Observation Period as the baseline and the total seizure frequency per 28 days of the Weeks, 12, 24, 32, 40, 52 and 52 LOCF as the post-treatment value. Percentage change in total seizure frequency was calculated as follows: \[100 x (post-treatment value - baseline)/ baseline\]. Seizures analyzed other than tonic-atonic seizures included: Partial seizure frequency, Absence seizure, Atypical absence seizure, Myoclonic seizure, Tonic seizure, Tonic-clonic seizure, Atonic seizure, and Unclassified epileptic seizure. This data was based on the diary data collected for 7 days after each visit. Seizure frequency was counted based on the classification established by the ILAE. The diary recorder monitored the participant and recorded the seizure diary in a consistent manner.
Time frame: Baseline (Observation period in Study 304), Week 12, Week 24, Week 32, Week 40, Week 52 and Week 52 LOCF
Population: Efficacy Analysis Set included all participants with evaluable efficacy data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Partial Seizure Week 24 | -80.9 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Partial Seizure Week 52 LOCF | -77.3 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Atypical Absence Seizure Week 52 | -100 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Tonic Seizure Week 32 | -49.4 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Partial Seizure Week 12 | -95 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Partial Seizure Week 32 | -70.5 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Partial Seizure Week 40 | -85.7 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Partial Seizure Week 52 | -77.3 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Absence Seizure Week 12 | -87.7 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Absence Seizure Week 24 | -100 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Absence Seizure Week 32 | -100 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Absence Seizure Week 40 | -100 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Absence Seizure Week 52 | -100 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Absence Seizure Week 52 LOCF | -100 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Atypical Absence Seizure Week 12 | -86.7 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Atypical Absence Seizure Week 24 | -92.85 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Atypical Absence Seizure Week 32 | -92.3 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Atypical Absence Seizure Week 40 | -100 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Atypical Absence Seizure Week 52 LOCF | -100 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Myoclonic Seizure Week 12 | -100 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Myoclonic Seizure Week 24 | -100 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Myoclonic Seizure Week 32 | -100 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Myoclonic Seizure Week 40 | -100 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Myoclonic Seizure Week 52 | -100 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Myoclonic Seizure Week 52 LOCF | -100 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Tonic Seizure Week 12 | -35.4 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Tonic Seizure Week 24 | -37.85 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Tonic Seizure Week 40 | -47.05 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Tonic Seizure Week 52 | -36.4 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Tonic Seizure Week 52 LOCF | -46.2 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Tonic-clonic Seizure Week 12 | -61.55 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Tonic-clonic Seizure Week 24 | -44.1 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Tonic-clonic Seizure Week 32 | -22.6 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Tonic-clonic Seizure Week 40 | -46.7 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Tonic-clonic Seizure Week 52 | -35.5 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Tonic-clonic Seizure Week 52 LOCF | -38.1 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Atonic Seizure Week 12 | -60.35 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Atonic Seizure Week 24 | -84.3 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Atonic Seizure Week 32 | -100 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Atonic Seizure Week 40 | -67.2 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Atonic Seizure Week 52 | -67.55 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Atonic Seizure Week 52 LOCF | -67.55 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Unclassified Seizure Week 12 | -100 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Unclassified Seizure Week 24 | 6932.3 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Unclassified Seizure Week 32 | -100 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Unclassified Seizure Week 40 | -100 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Unclassified Seizure Week 52 | -100 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures | Unclassified Seizure Week 52 LOCF | -100 Percent Change in Seizure Frequency |
Secondary
Percent Change in the Total Seizure Frequency From Baseline (Per 28 Days)
Percent change in the total seizure frequency (per 28 days) was calculated using the total seizure frequency per 28 days of the Observation Period of Study 304 as the baseline and the total seizure frequency per 28 days at Weeks 12, 24, 32, 40, 52 and Week 52 LOCF as the post-treatment value. Percentage change in total seizure frequency was calculated as follows: \[100 x (post-treatment value - baseline)/ baseline\].
Time frame: Baseline (Observation period in Study 304), Week 12, Week 24, Week 32, Week 40, Week 52 and Week 52 LOCF
Population: Efficacy Analysis Set included all participants with evaluable efficacy data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Rufinamide | Percent Change in the Total Seizure Frequency From Baseline (Per 28 Days) | Percent Change in Week 24 | -48.9 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Total Seizure Frequency From Baseline (Per 28 Days) | Percent Change in Week 32 | -50.6 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Total Seizure Frequency From Baseline (Per 28 Days) | Percent Change in Week 12 | -47.7 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Total Seizure Frequency From Baseline (Per 28 Days) | Percent Change in Week 40 | -52 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Total Seizure Frequency From Baseline (Per 28 Days) | Percent Change in Week 52 | -47.35 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in the Total Seizure Frequency From Baseline (Per 28 Days) | Percent Change in Week 52 LOCF | -46.3 Percent Change in Seizure Frequency |
Secondary
Percent Change in Tonic-Atonic Seizure Frequency From Baseline (Per 28 Days)
The sum of the frequencies of tonic seizures and atonic seizures was defined as the tonic-atonic seizure frequency. The percent change in tonic-atonic seizure frequency was calculated using the tonic-atonic seizure frequency per 28 days of the Observation Period in Study 304 as the baseline and the tonic-atonic seizure frequency at Weeks 12, 24, 32, 40, 52 and Week 52 Last Observation Carried Forward (LOCF) as the post-treatment value. Percentage change in tonic - atonic seizure frequency was calculated as follows: \[100 x (post-treatment value - baseline)/ baseline\]. The frequency of epileptic seizures was recorded in the seizure diary by the recorder. Seizure frequency was counted based on the classification established by the International League Against Epilepsy (ILAE). The diary recorder monitored the participant and recorded the seizure diary in a consistent manner, and continued these practices throughout the study period.
Time frame: Baseline (Observation period in Study 304), Week 12, Week 24, Week 32, Week 40, Week 52 and Week 52 LOCF
Population: Efficacy Analysis Set included all participants with evaluable efficacy data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Rufinamide | Percent Change in Tonic-Atonic Seizure Frequency From Baseline (Per 28 Days) | Percent Change in Week 52 LOCF | -39.25 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in Tonic-Atonic Seizure Frequency From Baseline (Per 28 Days) | Percent Change in Week 12 | -39.3 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in Tonic-Atonic Seizure Frequency From Baseline (Per 28 Days) | Percent Change in Week 24 | -40.6 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in Tonic-Atonic Seizure Frequency From Baseline (Per 28 Days) | Percent Change in Week 32 | -46.8 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in Tonic-Atonic Seizure Frequency From Baseline (Per 28 Days) | Percent Change in Week 40 | -47.6 Percent Change in Seizure Frequency |
| Rufinamide | Percent Change in Tonic-Atonic Seizure Frequency From Baseline (Per 28 Days) | Percent Change in Week 52 | -36.05 Percent Change in Seizure Frequency |