A Long Term Extension Study of E2080 in Lennox-Gastaut Patients

To investigate the safety of long term administration of E2080 in the patients with Lennox-Gastaut syndrome who completed the E2080-J081-304 Study.

Study Overview

• Status: Completed
• Conditions: Lennox-Gastaut Syndrome
• Intervention / Treatment: Drug: Rufinamide

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Okayama, Japan
  • Aichi
    • Nagoyashi, Aichi, Japan
  • Ehime
    • Matsuyama, Ehime, Japan
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan
  • Hiroshima
    • Hiroshima-shi, Hiroshima, Japan
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan
  • Hyogo
    • Kobe-shi, Hyogo, Japan
  • Kanagawa
    • Yokohama, Kanagawa, Japan
  • Kumamoto
    • Goshi^shi, Kumamoto, Japan
  • Miyagi
    • Iwanuma-shi, Miyagi, Japan
  • Nagasaki
    • Omura, Nagasaki, Japan
  • Nara
    • Nara-shi, Nara, Japan
  • Niigata
    • Niigata-shi, Niigata, Japan
  • Oita
    • Yufu-shi, Oita, Japan
  • Osaka
    • Neyagawa-shi, Osaka, Japan
    • Osaka-shi, Osaka, Japan
    • Suita-shi, Osaka, Japan
  • Shiga
    • Moriyama-shi, Shiga, Japan
  • Shizuoka
    • Shizuoka-shi, Shizuoka, Japan
  • Tokyo
    • Kodaira, Tokyo, Japan
    • Kokubunji-shi, Tokyo, Japan
    • Shinjuku, Tokyo, Japan
  • Toyama
    • Toyoma-shi, Toyama, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 30 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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.	Drug: Rufinamide; The target dosage is approximately 45 mg/kg/day, taken orally twice a day.; Other Names: E2080, BANZEL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From date of first dose up to 30 days after the last dose of study treatment, up to approximately 2 years 10 months

Secondary 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". 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.	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 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].	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	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.	Baseline (Observation period in Study 304), Week 12, Week 24, Week 32, Week 40, Week 52 and Week 52 LOCF
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.	Week 12, Week 24, Week 32, Week 40, Week 52 and Week 52 LOCF
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.	Week 12, Week 24, Week 32, Week 40, Week 52 and Week 52 LOCF

Collaborators and Investigators

• Sponsor: Eisai Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2010
• Primary Completion (ACTUAL): August 1, 2013
• Study Completion (ACTUAL): August 1, 2013

Study Registration Dates

• First Submitted: June 14, 2010
• First Submitted That Met QC Criteria: June 25, 2010
• First Posted (ESTIMATE): June 28, 2010

Study Record Updates

• Last Update Posted (ACTUAL): March 11, 2019
• Last Update Submitted That Met QC Criteria: November 15, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Epilepsy; Seizures
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes; Genetic Diseases, Inborn; Epilepsy; Lennox Gastaut Syndrome; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Rufinamide
• Other Study ID Numbers: E2080-J081-305