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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc. ( Eisai Limited )
ClinicalTrials.gov Identifier:
NCT01146951
First received: June 14, 2010
Last updated: January 29, 2014
Last verified: January 2014
  Purpose

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


Condition Intervention Phase
Lennox-Gastaut Syndrome
Drug: Rufinamide (E2080)
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Placebo-Controlled, Double-Blind Comparative Study of E2080 in Lennox-Gastaut Syndrome Patients

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Percent Change in Tonic-Atonic Seizure Frequency From Baseline (Per 28 Days) [ Time Frame: Baseline (28 day observational period) and End of Treatment (28 day treatment period) ] [ Designated as safety issue: No ]

    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 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline (28 day observational period) and End of Treatment (28 day treatment period) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline (28 day observational period) and End of Treatment (28 day treatment period) ] [ Designated as safety issue: No ]

    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) [ Time Frame: Up to Week 12 of the treatment period ] [ Designated as safety issue: No ]

    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.



Enrollment: 66
Study Start Date: June 2010
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rufinamide (E2080) Drug: Rufinamide (E2080)

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)

Other Name: E2080
Placebo Comparator: Placebo Drug: Placebo
Rufinamide Matching Placebo tablets administered orally twice daily after breakfast and dinner for a total of 12 weeks.

  Eligibility

Ages Eligible for Study:   4 Years to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  1. 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).
  2. Participants who had a slow spike-and-wave pattern in an electroencephalogram within 6 months prior to the enrollment for the Observation Period.
  3. Participants who had at least a total of 90 seizures in the 28 days prior to the enrollment for the Observation Period.
  4. 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.
  5. 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;

  1. Participants who had a history of generalized tonic-clonic status epilepticus within baseline.
  2. Participants who received drug therapy at least 4 times to be rescued from status epilepticus within baseline.
  3. Participants who had a history of hypoxia which needed emergency resuscitation within 12 months prior to the Treatment Period.
  4. 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.
  5. Participants who had a history of suicide attempt within the 1 year prior to the Treatment Period.
  6. Participants who had a history of or has an allergy to triazole compound.
  7. Participants who have clinically significant electrocardiogram abnormalities at baseline.
  8. Participants who are pregnant, who may be pregnant, who are lactating or who wish to be pregnant.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01146951

Locations
Japan
Nagoya-shi, Aichi, Japan
Matsuyama-shi, Ehime, Japan
Fukuoka-shi, Fukuoka, Japan
Hiroshima-shi, Hiroshima, Japan
Sapporo-shi, Hokkaido, Japan
Kobe-shi, Hyogo, Japan
Yokohama-shi, Kanagawa, Japan
Goshi-shi, Kumamoto, Japan
Iwamuma-shi, Miyagi, Japan
Omura-shi, Nagasaki, Japan
Nara-shi, Nara, Japan
Niigata-shi, Niigata, Japan
Yufu-shi, Oita, Japan
Okayama-shi, Okayama, Japan
Neyagawa-shi, Osaka, Japan
Osaka-shi, Osaka, Japan
Suita-shi, Osaka, Japan
Moriya-shi, Shiga, Japan
Shizuoka-shi, Shizuoka, Japan
Kodaira-shi, Tokyo, Japan
Kokubunji-shi, Tokyo, Japan
Shinjuku-ku, Tokyo, Japan
Toyoma-shi, Toyama, Japan
Sponsors and Collaborators
Eisai Limited
Investigators
Study Director: Hiroki Takano Neuroscience Clinical Development Section. JAC PCU. Eisai Co., Ltd.
  More Information

No publications provided

Responsible Party: Eisai Inc. ( Eisai Limited )
ClinicalTrials.gov Identifier: NCT01146951     History of Changes
Other Study ID Numbers: E2080-J081-304
Study First Received: June 14, 2010
Results First Received: May 13, 2013
Last Updated: January 29, 2014
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Eisai Inc.:
Epilepsy
Seizures

Additional relevant MeSH terms:
Spasms, Infantile
Syndrome
Intellectual Disability
Disease
Pathologic Processes
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Mental Disorders Diagnosed in Childhood
Mental Disorders
Epilepsy, Generalized
Epilepsy
Brain Diseases
Central Nervous System Diseases

ClinicalTrials.gov processed this record on September 16, 2014