Trial Outcomes & Findings for A Long Term Extension Study of E2080 in Lennox-Gastaut Patients (NCT NCT01151540)
NCT ID: NCT01151540
Last Updated: 2019-03-11
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
54 participants
Primary outcome timeframe
From date of first dose up to 30 days after the last dose of study treatment, up to approximately 2 years 10 months
Results posted on
2019-03-11
Participant Flow
Participants who successfully completed Study 304 were enrolled into this study.
Participant milestones
| Measure |
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.
|
|---|---|
|
Overall Study
STARTED
|
54
|
|
Overall Study
COMPLETED
|
41
|
|
Overall Study
NOT COMPLETED
|
13
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|
|
Overall Study
Other
|
2
|
|
Overall Study
Adverse event, non-fatal
|
4
|
|
Overall Study
Withdrawal by Subject
|
7
|
Baseline Characteristics
A Long Term Extension Study of E2080 in Lennox-Gastaut Patients
Baseline characteristics by cohort
| Measure |
Rufinamide
n=54 Participants
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.
|
|---|---|
|
Age, Continuous
|
15 Years
STANDARD_DEVIATION 6.8 • n=5 Participants
|
|
Age, Customized
≥4 to <12 years
|
22 Participants
n=5 Participants
|
|
Age, Customized
≥12 to <17 years
|
11 Participants
n=5 Participants
|
|
Age, Customized
≥17 years
|
21 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
21 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
33 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From date of first dose up to 30 days after the last dose of study treatment, up to approximately 2 years 10 monthsPopulation: Safety analysis set included all treated participants.
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.
Outcome measures
| Measure |
Rufinamide
n=54 Participants
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.
|
|---|---|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Rufinamide
TEAEs
|
54 Participants
|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Rufinamide
Treatment-related TEAEs
|
38 Participants
|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Rufinamide
SAEs
|
9 Participants
|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Rufinamide
Treatment-related SAEs
|
2 Participants
|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Rufinamide
AEs leading to study drug withdrawal
|
3 Participants
|
|
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 outcome
Timeframe: Baseline (Observation period in Study 304), Week 12, Week 24, Week 32, Week 40, Week 52 and Week 52 LOCFPopulation: Efficacy Analysis Set included all participants with evaluable efficacy data.
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.
Outcome measures
| Measure |
Rufinamide
n=46 Participants
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.
|
|---|---|
|
Percent Change in Tonic-Atonic Seizure Frequency From Baseline (Per 28 Days)
Percent Change in Week 12
|
-39.3 Percent Change in Seizure Frequency
Interval -100.0 to 125.2
|
|
Percent Change in Tonic-Atonic Seizure Frequency From Baseline (Per 28 Days)
Percent Change in Week 24
|
-40.6 Percent Change in Seizure Frequency
Interval -100.0 to 85.7
|
|
Percent Change in Tonic-Atonic Seizure Frequency From Baseline (Per 28 Days)
Percent Change in Week 32
|
-46.8 Percent Change in Seizure Frequency
Interval -100.0 to 75.0
|
|
Percent Change in Tonic-Atonic Seizure Frequency From Baseline (Per 28 Days)
Percent Change in Week 40
|
-47.6 Percent Change in Seizure Frequency
Interval -100.0 to 833.2
|
|
Percent Change in Tonic-Atonic Seizure Frequency From Baseline (Per 28 Days)
Percent Change in Week 52
|
-36.05 Percent Change in Seizure Frequency
Interval -100.0 to 101.7
|
|
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
Interval -100.0 to 101.7
|
SECONDARY outcome
Timeframe: Baseline (Observation period in Study 304), Week 12, Week 24, Week 32, Week 40, Week 52 and Week 52 LOCFPopulation: Efficacy Analysis Set included all participants with evaluable efficacy data.
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: \[100 x (post-treatment value - baseline)/ baseline\].
Outcome measures
| Measure |
Rufinamide
n=46 Participants
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.
|
|---|---|
|
Percent Change in the Total Seizure Frequency From Baseline (Per 28 Days)
Percent Change in Week 12
|
-47.7 Percent Change in Seizure Frequency
Interval -100.0 to 101.5
|
|
Percent Change in the Total Seizure Frequency From Baseline (Per 28 Days)
Percent Change in Week 24
|
-48.9 Percent Change in Seizure Frequency
Interval -97.0 to 116.6
|
|
Percent Change in the Total Seizure Frequency From Baseline (Per 28 Days)
Percent Change in Week 32
|
-50.6 Percent Change in Seizure Frequency
Interval -90.8 to 209.2
|
|
Percent Change in the Total Seizure Frequency From Baseline (Per 28 Days)
Percent Change in Week 40
|
-52 Percent Change in Seizure Frequency
Interval -95.5 to 833.2
|
|
Percent Change in the Total Seizure Frequency From Baseline (Per 28 Days)
Percent Change in Week 52
|
-47.35 Percent Change in Seizure Frequency
Interval -94.3 to 340.8
|
|
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
Interval -100.0 to 340.8
|
SECONDARY outcome
Timeframe: Baseline (Observation period in Study 304), Week 12, Week 24, Week 32, Week 40, Week 52 and Week 52 LOCFPopulation: Efficacy Analysis Set included all participants with evaluable efficacy data.
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.
Outcome measures
| Measure |
Rufinamide
n=45 Participants
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.
|
|---|---|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Partial Seizure Week 12
|
-95 Percent Change in Seizure Frequency
Interval -100.0 to 255.6
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Partial Seizure Week 24
|
-80.9 Percent Change in Seizure Frequency
Interval -100.0 to 303.2
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Partial Seizure Week 32
|
-70.5 Percent Change in Seizure Frequency
Interval -100.0 to 30.2
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Partial Seizure Week 40
|
-85.7 Percent Change in Seizure Frequency
Interval -100.0 to -42.4
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Partial Seizure Week 52
|
-77.3 Percent Change in Seizure Frequency
Interval -100.0 to -61.8
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Partial Seizure Week 52 LOCF
|
-77.3 Percent Change in Seizure Frequency
Interval -100.0 to 189.2
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Absence Seizure Week 12
|
-87.7 Percent Change in Seizure Frequency
Interval -87.7 to -87.7
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Absence Seizure Week 24
|
-100 Percent Change in Seizure Frequency
Interval -100.0 to -100.0
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Absence Seizure Week 32
|
-100 Percent Change in Seizure Frequency
Interval -100.0 to -100.0
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Absence Seizure Week 40
|
-100 Percent Change in Seizure Frequency
Interval -100.0 to -100.0
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Absence Seizure Week 52
|
-100 Percent Change in Seizure Frequency
Interval -100.0 to -100.0
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Absence Seizure Week 52 LOCF
|
-100 Percent Change in Seizure Frequency
Interval -100.0 to -100.0
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Atypical Absence Seizure Week 12
|
-86.7 Percent Change in Seizure Frequency
Interval -100.0 to 54.7
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Atypical Absence Seizure Week 24
|
-92.85 Percent Change in Seizure Frequency
Interval -100.0 to 185.7
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Atypical Absence Seizure Week 32
|
-92.3 Percent Change in Seizure Frequency
Interval -100.0 to 209.2
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Atypical Absence Seizure Week 40
|
-100 Percent Change in Seizure Frequency
Interval -100.0 to 219.3
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Atypical Absence Seizure Week 52
|
-100 Percent Change in Seizure Frequency
Interval -100.0 to 737.2
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Atypical Absence Seizure Week 52 LOCF
|
-100 Percent Change in Seizure Frequency
Interval -100.0 to 737.2
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Myoclonic Seizure Week 12
|
-100 Percent Change in Seizure Frequency
Interval -100.0 to 228.8
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Myoclonic Seizure Week 24
|
-100 Percent Change in Seizure Frequency
Interval -100.0 to 64.4
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Myoclonic Seizure Week 32
|
-100 Percent Change in Seizure Frequency
Interval -100.0 to 435.6
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Myoclonic Seizure Week 40
|
-100 Percent Change in Seizure Frequency
Interval -100.0 to 117.6
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Myoclonic Seizure Week 52
|
-100 Percent Change in Seizure Frequency
Interval -100.0 to 368.2
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Myoclonic Seizure Week 52 LOCF
|
-100 Percent Change in Seizure Frequency
Interval -100.0 to 368.2
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Tonic Seizure Week 12
|
-35.4 Percent Change in Seizure Frequency
Interval -100.0 to 175.2
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Tonic Seizure Week 24
|
-37.85 Percent Change in Seizure Frequency
Interval -100.0 to 138.5
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Tonic Seizure Week 32
|
-49.4 Percent Change in Seizure Frequency
Interval -100.0 to 83.5
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Tonic Seizure Week 40
|
-47.05 Percent Change in Seizure Frequency
Interval -100.0 to 833.2
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Tonic Seizure Week 52
|
-36.4 Percent Change in Seizure Frequency
Interval -100.0 to 110.2
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Tonic Seizure Week 52 LOCF
|
-46.2 Percent Change in Seizure Frequency
Interval -100.0 to 110.2
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Tonic-clonic Seizure Week 12
|
-61.55 Percent Change in Seizure Frequency
Interval -100.0 to 300.0
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Tonic-clonic Seizure Week 24
|
-44.1 Percent Change in Seizure Frequency
Interval -100.0 to 300.0
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Tonic-clonic Seizure Week 32
|
-22.6 Percent Change in Seizure Frequency
Interval -100.0 to 700.0
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Tonic-clonic Seizure Week 40
|
-46.7 Percent Change in Seizure Frequency
Interval -100.0 to 1100.0
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Tonic-clonic Seizure Week 52
|
-35.5 Percent Change in Seizure Frequency
Interval -100.0 to 700.0
|
|
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
Interval -100.0 to 700.0
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Atonic Seizure Week 12
|
-60.35 Percent Change in Seizure Frequency
Interval -100.0 to 29.0
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Atonic Seizure Week 24
|
-84.3 Percent Change in Seizure Frequency
Interval -100.0 to 189.2
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Atonic Seizure Week 32
|
-100 Percent Change in Seizure Frequency
Interval -100.0 to 20.5
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Atonic Seizure Week 40
|
-67.2 Percent Change in Seizure Frequency
Interval -100.0 to 261.4
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Atonic Seizure Week 52
|
-67.55 Percent Change in Seizure Frequency
Interval -100.0 to 526.5
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Atonic Seizure Week 52 LOCF
|
-67.55 Percent Change in Seizure Frequency
Interval -100.0 to 526.5
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Unclassified Seizure Week 12
|
-100 Percent Change in Seizure Frequency
Interval -100.0 to -100.0
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Unclassified Seizure Week 24
|
6932.3 Percent Change in Seizure Frequency
Interval 6932.3 to 6932.3
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Unclassified Seizure Week 32
|
-100 Percent Change in Seizure Frequency
Interval -100.0 to -100.0
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Unclassified Seizure Week 40
|
-100 Percent Change in Seizure Frequency
Interval -100.0 to -100.0
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Unclassified Seizure Week 52
|
-100 Percent Change in Seizure Frequency
Interval -100.0 to -100.0
|
|
Percent Change in the Frequency of Seizures Other Than Tonic-Atonic Seizures
Unclassified Seizure Week 52 LOCF
|
-100 Percent Change in Seizure Frequency
Interval -100.0 to -100.0
|
SECONDARY outcome
Timeframe: Week 12, Week 24, Week 32, Week 40, Week 52 and Week 52 LOCFPopulation: Efficacy Analysis Set included all participants with evaluable efficacy data.
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.
Outcome measures
| Measure |
Rufinamide
n=46 Participants
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.
|
|---|---|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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 outcome
Timeframe: Week 12, Week 24, Week 32, Week 40, Week 52 and Week 52 LOCFPopulation: Efficacy Analysis Set included all participants with evaluable efficacy data.
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.
Outcome measures
| Measure |
Rufinamide
n=46 Participants
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.
|
|---|---|
|
Percentage of Participants With An Increase In Tonic-Atonic Seizure Frequency
Week 32 Increase - Yes
|
16.7 Percentage of participants
|
|
Percentage of Participants With An Increase In Tonic-Atonic Seizure Frequency
Week 12 Increase - Yes
|
21.7 Percentage of participants
|
|
Percentage of Participants With An Increase In Tonic-Atonic Seizure Frequency
Week 12 Increase - No
|
78.3 Percentage of participants
|
|
Percentage of Participants With An Increase In Tonic-Atonic Seizure Frequency
Week 24 Increase - Yes
|
23.3 Percentage of participants
|
|
Percentage of Participants With An Increase In Tonic-Atonic Seizure Frequency
Week 24 Increase - No
|
76.7 Percentage of participants
|
|
Percentage of Participants With An Increase In Tonic-Atonic Seizure Frequency
Week 32 Increase - No
|
83.3 Percentage of participants
|
|
Percentage of Participants With An Increase In Tonic-Atonic Seizure Frequency
Week 40 Increase - Yes
|
9.8 Percentage of participants
|
|
Percentage of Participants With An Increase In Tonic-Atonic Seizure Frequency
Week 40 Increase - No
|
90.2 Percentage of participants
|
|
Percentage of Participants With An Increase In Tonic-Atonic Seizure Frequency
Week 52 Increase - Yes
|
22.5 Percentage of participants
|
|
Percentage of Participants With An Increase In Tonic-Atonic Seizure Frequency
Week 52 Increase -No
|
77.5 Percentage of participants
|
|
Percentage of Participants With An Increase In Tonic-Atonic Seizure Frequency
Week 52 LOCF Increase - Yes
|
19.6 Percentage of participants
|
|
Percentage of Participants With An Increase In Tonic-Atonic Seizure Frequency
Week 52 LOCF Increase - No
|
80.4 Percentage of participants
|
Adverse Events
Rufinamide
Serious events: 9 serious events
Other events: 54 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Rufinamide
n=54 participants at risk
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.
|
|---|---|
|
Injury, poisoning and procedural complications
Contusion
|
1.9%
1/54 • Number of events 1 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Nervous system disorders
Status epilepticus
|
3.7%
2/54 • Number of events 4 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Gastrointestinal disorders
Dental caries
|
1.9%
1/54 • Number of events 1 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Infections and infestations
Pneumonia
|
7.4%
4/54 • Number of events 6 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Infections and infestations
Upper respiratory tract infection
|
1.9%
1/54 • Number of events 1 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Infections and infestations
Influenza
|
1.9%
1/54 • Number of events 1 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Infections and infestations
Gastroenteritis viral
|
1.9%
1/54 • Number of events 1 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
Other adverse events
| Measure |
Rufinamide
n=54 participants at risk
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.
|
|---|---|
|
Injury, poisoning and procedural complications
Contusion
|
22.2%
12/54 • Number of events 22 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Injury, poisoning and procedural complications
Skin laceration
|
9.3%
5/54 • Number of events 9 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Injury, poisoning and procedural complications
Eyelid injury
|
7.4%
4/54 • Number of events 5 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Injury, poisoning and procedural complications
Fall
|
7.4%
4/54 • Number of events 4 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Injury, poisoning and procedural complications
Mouth injury
|
7.4%
4/54 • Number of events 4 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Investigations
Platelet count decreased
|
5.6%
3/54 • Number of events 3 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Investigations
Weight decreased
|
5.6%
3/54 • Number of events 3 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
11.1%
6/54 • Number of events 9 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Nervous system disorders
Status epilepticus
|
40.7%
22/54 • Number of events 158 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Nervous system disorders
Somnolence
|
25.9%
14/54 • Number of events 17 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Nervous system disorders
Dizziness
|
5.6%
3/54 • Number of events 4 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Eye disorders
Conjunctivitis allergic
|
5.6%
3/54 • Number of events 4 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
General disorders
Pyrexia
|
9.3%
5/54 • Number of events 12 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Psychiatric disorders
Insomnia
|
11.1%
6/54 • Number of events 6 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Psychiatric disorders
Agitation
|
7.4%
4/54 • Number of events 4 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Gastrointestinal disorders
Vomiting
|
24.1%
13/54 • Number of events 27 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Gastrointestinal disorders
Constipation
|
16.7%
9/54 • Number of events 10 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Gastrointestinal disorders
Dental caries
|
13.0%
7/54 • Number of events 8 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Gastrointestinal disorders
Stomatitis
|
11.1%
6/54 • Number of events 6 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Gastrointestinal disorders
Nausea
|
7.4%
4/54 • Number of events 4 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Gastrointestinal disorders
Diarrhoea
|
5.6%
3/54 • Number of events 3 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
5.6%
3/54 • Number of events 4 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
5.6%
3/54 • Number of events 3 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.6%
3/54 • Number of events 3 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
13.0%
7/54 • Number of events 7 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Infections and infestations
Nasopharyngitis
|
48.1%
26/54 • Number of events 61 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Infections and infestations
Influenza
|
20.4%
11/54 • Number of events 15 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Infections and infestations
Upper respiratory tract infection
|
11.1%
6/54 • Number of events 16 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Infections and infestations
Bronchitis
|
9.3%
5/54 • Number of events 9 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Infections and infestations
Gastroenteritis
|
9.3%
5/54 • Number of events 5 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
|
Infections and infestations
Pharyngitis
|
7.4%
4/54 • Number of events 6 • From date of first dose up to 15 days after the last dose of study treatment, up to approximately 2 years and 10 months
Safety analysis set included all treated participants.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER