Back to resultsA Placebo-Controlled, Double-Blind Comparative Study of E2080 in Lennox-Gastaut Syndrome Patients (Study E2080-J081-304)
Primary Purpose
Lennox-Gastaut Syndrome
Status
Completed
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
Rufinamide (E2080)
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Lennox-Gastaut Syndrome focused on measuring Epilepsy, Seizures
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Rufinamide (E2080)
Placebo
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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].
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01146951
Brief Title
A Placebo-Controlled, Double-Blind Comparative Study of E2080 in Lennox-Gastaut Syndrome Patients (Study E2080-J081-304)
Official Title
A Placebo-Controlled, Double-Blind Comparative Study of E2080 in Lennox-Gastaut Syndrome Patients
Study Type
Interventional
2. Study Status
Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
June 2010 (undefined)
Primary Completion Date
August 2011 (Actual)
Study Completion Date
August 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eisai Limited
4. Oversight
5. Study Description
Brief Summary
To confirm that the combination therapy of rufinamide has superior efficacy compared to placebo in patients with Lennox-Gastaut syndrome.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lennox-Gastaut Syndrome
Keywords
Epilepsy, Seizures
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
66 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rufinamide (E2080)
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Rufinamide (E2080)
Other Intervention Name(s)
E2080
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Rufinamide Matching Placebo tablets administered orally twice daily after breakfast and dinner for a total of 12 weeks.
Primary Outcome Measure Information:
Title
Percent Change in Tonic-Atonic Seizure Frequency From Baseline (Per 28 Days)
Description
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.
Time Frame
Baseline (28 day observational period) and End of Treatment (28 day treatment period)
Secondary Outcome Measure Information:
Title
Number of Participants Achieving a 50% Reduction in Tonic-atonic Seizure Frequency
Description
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.
Time Frame
12 weeks
Title
Percent Change in Total Seizure Frequency (Per 28 Days)
Description
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].
Time Frame
Baseline (28 day observational period) and End of Treatment (28 day treatment period)
Title
Percentage Change in the Frequency of Seizures Other Than Tonic-atonic Seizures (Per 28 Days)
Description
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.
Time Frame
Baseline (28 day observational period) and End of Treatment (28 day treatment period)
Title
Clinical Global Impression of Change (CGIC)
Description
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.
Time Frame
Up to Week 12 of the treatment period
10. Eligibility
Sex
All
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hiroki Takano
Organizational Affiliation
Neuroscience Clinical Development Section. JAC PCU. Eisai Co., Ltd.
Official's Role
Study Director
Facility Information:
City
Nagoya-shi
State/Province
Aichi
Country
Japan
City
Matsuyama-shi
State/Province
Ehime
Country
Japan
City
Fukuoka-shi
State/Province
Fukuoka
Country
Japan
City
Hiroshima-shi
State/Province
Hiroshima
Country
Japan
City
Sapporo-shi
State/Province
Hokkaido
Country
Japan
City
Kobe-shi
State/Province
Hyogo
Country
Japan
City
Yokohama-shi
State/Province
Kanagawa
Country
Japan
City
Goshi-shi
State/Province
Kumamoto
Country
Japan
City
Iwamuma-shi
State/Province
Miyagi
Country
Japan
City
Omura-shi
State/Province
Nagasaki
Country
Japan
City
Nara-shi
State/Province
Nara
Country
Japan
City
Niigata-shi
State/Province
Niigata
Country
Japan
City
Yufu-shi
State/Province
Oita
Country
Japan
City
Okayama-shi
State/Province
Okayama
Country
Japan
City
Neyagawa-shi
State/Province
Osaka
Country
Japan
City
Osaka-shi
State/Province
Osaka
Country
Japan
City
Suita-shi
State/Province
Osaka
Country
Japan
City
Moriya-shi
State/Province
Shiga
Country
Japan
City
Shizuoka-shi
State/Province
Shizuoka
Country
Japan
City
Kodaira-shi
State/Province
Tokyo
Country
Japan
City
Kokubunji-shi
State/Province
Tokyo
Country
Japan
City
Shinjuku-ku
State/Province
Tokyo
Country
Japan
City
Toyoma-shi
State/Province
Toyama
Country
Japan
12. IPD Sharing Statement
Citations:
PubMed Identifier
33825230
Citation
Brigo F, Jones K, Eltze C, Matricardi S. Anti-seizure medications for Lennox-Gastaut syndrome. Cochrane Database Syst Rev. 2021 Apr 7;4(4):CD003277. doi: 10.1002/14651858.CD003277.pub4.
Results Reference
derived
PubMed Identifier
33179247
Citation
Panebianco M, Prabhakar H, Marson AG. Rufinamide add-on therapy for drug-resistant epilepsy. Cochrane Database Syst Rev. 2020 Nov 8;11(11):CD011772. doi: 10.1002/14651858.CD011772.pub3.
Results Reference
derived
Learn more about this trial
A Placebo-Controlled, Double-Blind Comparative Study of E2080 in Lennox-Gastaut Syndrome Patients (Study E2080-J081-304)
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