A Placebo-Controlled, Double-Blind Comparative Study of E2080 in Lennox-Gastaut Syndrome Patients (Study E2080-J081-304)

Study Overview
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Brief Summary
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To confirm that the combination therapy of rufinamide has superior efficacy compared to placebo in patients with Lennox-Gastaut syndrome.

Official Title
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A Placebo-Controlled, Double-Blind Comparative Study of E2080 in Lennox-Gastaut Syndrome Patients

Conditions
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Lennox-Gastaut Syndrome

Intervention / Treatment
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* Drug: Rufinamide (E2080)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Participants who are diagnosed as Lennox-Gastaut syndrome with tonic/atonic seizures and atypical absence seizures (A history of atypical absence seizures will also be incorporated). Participants who had a slow spike-and-wave pattern in an electroencephalogram within 6 months prior to the enrollment for the Observation Period. Participants who had at least a total of 90 seizures in the 28 days prior to the enrollment for the Observation Period. Participants who have been on 1 - 3 anti-epileptic drugs from 28 days prior to the enrollment for the Observation Period and have not changed the type of the anti-epileptic drugs. Participants who have not changed the type nor the dose or administration of the anti-epileptic drugs they are taking in the Observation Period. Exclusion criteria; Participants who had a history of generalized tonic-clonic status epilepticus within baseline. Participants who received drug therapy at least 4 times to be rescued from status epilepticus within baseline. Participants who had a history of hypoxia which needed emergency resuscitation within 12 months prior to the Treatment Period. Participants who were on a ketogenic diet or have received adrenocorticotropic hormone (ACTH) therapy or Vitamin B6 therapy within 6 months prior to the Treatment Period. Participants who had a history of suicide attempt within the 1 year prior to the Treatment Period. Participants who had a history of or has an allergy to triazole compound. Participants who have clinically significant electrocardiogram abnormalities at baseline. Participants who are pregnant, who may be pregnant, who are lactating or who wish to be pregnant.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rufinamide (E2080)<br> | Drug: Rufinamide (E2080)<br>* Rufinamide tablets administered orally twice daily after breakfast and dinner. Treatment was divided into a Dose Titration Period (2 weeks) and a Dose Maintenance Period (10 weeks). As a general rule, the dose was increased by 1 step every 2 days until it reached the target maintenance dose determined by body weight at the start of the Observation Period. Target maintenance dose: 15.0 - 30.0 kg: 1000 mg/day (5 tablets each in the morning and evening) 30.1 - 50.0 kg: 1800 mg/day (4 tablets in the morning and 5 in the evening) 50.1 - 70.0 kg: 2400 mg/day (6 tablets each in the morning and evening) >= 70.1 kg: 3200 mg/day (8 tablets each in the morning and evening)<br>* Other names: E2080;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Rufinamide Matching Placebo tablets administered orally twice daily after breakfast and dinner for a total of 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 and the percent change in tonic-atonic seizure frequency per 28 days was assessed. The percent change in tonic-atonic seizure frequency was calculated using the tonic-atonic seizure frequency per 28 days of the Observation Period as the baseline and the tonic-atonic seizure frequency per 28 days of the Treatment Period 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. | Baseline (28 day observational period) and End of Treatment (28 day treatment period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Achieving a 50% Reduction in Tonic-atonic Seizure Frequency | 50% Responder Rate in Tonic-Atonic Seizure Frequency was presented as the number of participants who achieved a 50% reduction in tonic-atonic seizure frequency. | 12 weeks | 
| Percent Change in Total Seizure Frequency (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 as the baseline and the total seizure frequency per 28 days of the Treatment Period as the post-treatment value. Percentage change in total seizure frequency was calculated as follows: [100 x (post-treatment value - baseline)/ baseline]. | Baseline (28 day observational period) and End of Treatment (28 day treatment period) | 
| Percentage Change in the Frequency of Seizures Other Than Tonic-atonic Seizures (Per 28 Days) | 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 Treatment Period 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 freq. (frequency), Absence seizure, Atyp. (atypical) absence seizure, Myoclonic seizure, Clonic seizure, Tonic seizure, Tonic-clonic seizure, Atonic seizure, & Uncla. (unclassified) epileptic seizure. The frequency of epileptic seizures was recorded in the 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. | Baseline (28 day observational period) and End of Treatment (28 day treatment period) | 
| Clinical Global Impression of Change (CGIC) | CGIC in participants with Lennox-Gastaut Syndrome (LGS) relative to placebo was presented as number of participants in each category at the final assessment (last observation carried forward [LOCF]) & at Week 12 of the Treatment Period. The investigator assessed the CGIC by comparing the participants' condition during the 4 weeks immediately before the completion (or discontinuation [d/c]) of the Treatment Period to his/her condition during the 4-week Observation Period (for participants who d/c'd the study during the Treatment Period, the CGIC was assessed by comparing the participant's condition from the start to discontinuation of the study treatment to his/her condition during the 4-week Observation Period). The CGIC was assessed according to the following 7-grade scale based on the frequency & severity of seizures, AEs, and overall conditions of daily life. Markedly improved, Improved, Slightly improved, Unchanged, Slightly worsened, Worsened, Markedly worsened. | Up to Week 12 of the treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epilepsy, Seizures