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Study of Rufinamide in Pediatric Subjects 1 to Less Than 4 Years of Age With Lennox-Gastaut Syndrome Inadequately Controlled With Other Anti-epileptic Drugs

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ClinicalTrials.gov Identifier: NCT01405053
Recruitment Status : Completed
First Posted : July 29, 2011
Results First Posted : August 6, 2019
Last Update Posted : August 6, 2019
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.

Brief Summary:
This study was designed to evaluate the cognitive effect, safety, and pharmacokinetics (PK) of rufinamide on Lennox-Gastaut Syndrome (LGS) inadequately controlled in pediatric participants already taking other anti-epileptic drugs.

Condition or disease Intervention/treatment Phase
Lennox-Gastaut Syndrome Drug: Rufinamide Drug: Any other approved Antiepileptic Drug Phase 3

Expanded Access : Eisai Inc. has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.  

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Controlled, Open-label Study to Evaluate the Cognitive Development Effects and Safety, and Pharmacokinetics of Adjunctive Rufinamide Treatment in Pediatric Subjects 1 to Less Than 4 Years of Age With Inadequately Controlled Lennox-Gastaut Syndrome
Actual Study Start Date : June 16, 2011
Actual Primary Completion Date : November 2, 2015
Actual Study Completion Date : November 2, 2015


Arm Intervention/treatment
Active Comparator: Rufinamide Drug: Rufinamide
Rufinamide up to 45 mg/kg/day, in 2 divided doses, administered as oral suspension (40 mg/mL) as an add-on to the subject's existing regimen of 1-3 antiepileptic drugs (AEDs)

Active Comparator: Any other approved AED Drug: Any other approved Antiepileptic Drug
Any other approved AED: any other approved AED of the investigator's choice as an add-on to the subject's existing regimen of 1-3 anti-epileptic drugs (AEDs)




Primary Outcome Measures :
  1. Child Behavior Checklist (CBCL) Total Problem T-scores at the End of 2-year Treatment Period [ Time Frame: End of Treatment Period (up to approximately Week 106) ]
    CBCL: 99-item questionnaire measures specific behavioral problems or developmental delays, answered by a parent/legal guardian or suitable caregiver. Each item were rated using 3-point scale (0=Not True, 1=Somewhat/Sometimes True, 2=Very True/ Often True) to indicate how often or typical the behavior was. The 99 items were combined to yield scores for 8 problem area scales (emotionally reactive, anxious/depressed, somatic complaints, withdrawn, sleep problems, attention problems, aggressive behavior, and other problems) and 3 summary scores (internalizing, externalizing, and total problems). Total Problem score was sum of all the problem areas plus 1 additional item, ranging from 0 to 198. Total raw scores are converted to t-scores with mean of 50 and standard deviation (SD) of 10. T-scores were standardized test scores that indicate same degree of elevation in problems relative to the normative sample of peers. Higher scores were indicative of more problems.

  2. Change From Baseline in CBCL Total Problem T-Scores at End of 2-year Treatment Period [ Time Frame: Baseline and End of Treatment Period (up to approximately Week 106) ]
    CBCL: 99-item questionnaire measures specific behavioral problems or developmental delays, answered by a parent/legal guardian or suitable caregiver. Each item were rated using 3-point scale (0=Not True, 1=Somewhat/Sometimes True, 2=Very True/ Often True) to indicate how often or typical the behavior was. The 99 items were combined to yield scores for 8 problem area scales (emotionally reactive, anxious/depressed, somatic complaints, withdrawn, sleep problems, attention problems, aggressive behavior, and other problems) and 3 summary scores (internalizing, externalizing, and total problems). Total Problem score was sum of all the problem areas plus 1 additional item, ranging from 0 to 198. Total raw scores are converted to t-scores with mean of 50 and standard deviation (SD) of 10. T-scores were standardized test scores that indicate same degree of elevation in problems relative to the normative sample of peers. Higher scores were indicative of more problems.


Other Outcome Measures:
  1. Time to Withdrawal From Treatment Due to an Adverse Event or Lack of Efficacy [ Time Frame: Baseline up to the End of the Treatment Period (up to approximately Week 106) ]
    Withdrawal from either rufinamide or other AED was due to the occurrence of an adverse event or for lack of efficacy. Data was obtained till Week 106 and was extrapolated using Kaplan-Meier method to determine the overall survival time (in weeks) to withdrawal from treatment (excluding taper) due to an adverse event or lack efficacy.

  2. Percent Change in Total Seizure Frequency Per 28 Days [ Time Frame: Baseline up to End of the Treatment Period (up to approximately Week 106) ]
    The frequency per 28 days was defined as (S/D)*28 where, S was equal to the sum of the seizures reported in the participant seizure diary during the specified time interval and D was equal to the number of days with non-missing data in the participant seizure diary for the specified study phase. The number of seizures was assessed and recorded by the participant's parent(s)/caregiver(s) in the participant seizure diary.

  3. Percent Change in Seizure Frequency by Individual Seizure Type Per 28 Days [ Time Frame: Baseline up to End of Treatment Period (up to approximately Week 106) ]
    The frequency per 28 days was defined as (S/D)*28 where, S was equal to the sum of the seizures reported in the participant seizure diary during the specified time interval and D was equal to the number of days with non-missing data in the participant seizure diary for the specified study phase. The number of seizures was assessed and recorded by the participant's parent(s)/caregiver(s) in the participant seizure diary.

  4. Incidence of Worsening of Seizures [ Time Frame: Baseline up to End of Treatment Period (up to approximately Week 106) ]
    Worsening of seizures was summarized by the incidence of participants with doubling in total seizure frequency, doubling in frequency of major seizures (generalized tonic-clonic, drop attacks), or occurrence of new seizure type during each successive 3 to 4 month visit interval of the Maintenance Period relative to baseline.

  5. Change From Baseline in CBCL Sub Scores at Week 106 [ Time Frame: Baseline and Week 106 ]
    CBCL: 99-item questionnaire, measures behavioral problems/developmental delays, answered by parent/guardian/caregiver. Each item rated on 3-point scale (0=Not True,1=Somewhat/Sometimes True, 2=Very/Often True). 99 items were combined to give scores for 8 problem area scales, where 1 for each 8 syndrome (emotionally reactive, anxious/depressed, somatic, withdrawn, sleep, attention, aggressive behavior, and other problems) were calculated, range: 0 (normal) to 16 (clinical behavior) and 3 summary scores (internalizing, externalizing, and total problems). All 3 summary scores reported scaled to T-scores. Total Problem score was sum of all the problem areas plus 1 additional item, ranging from 0 to 198. Total raw score were converted to t-scores with mean of 50 and SD of 10. T-scores were standardized test scores that indicate same degree of elevation in problems relative to normative sample of peers. Higher scores were indicative of more problems.

  6. Change From Baseline in Language Development Survey (LDS) Scores During Maintenance Period [ Time Frame: Baseline, Weeks 24, 56, 88, and 106 ]
    LDS, a caregiver-administered survey consisted of 8-item questionnaire and vocabulary list of 310 words organized within 14 semantic categories. List contained high frequency words (e.g. more), less common words (e.g. hamburger), and lexical chunks (e.g. Sesame Street). Average LDS score, calculated by dividing total number of words across all valid phrases by number of phrases with greater than (>) 0words; for participants with no words, average was 0. This value was compared to standardized chart to obtain percentile rating. LDS provided 2 scores: average phrase length (number of words/phrase) and number of endorsed vocabulary words. LDS phrase length was categorized into delay (less than or equal to [<=] 20th percentile) and no delay (>20th percentile). LDS vocabulary was categorized into delay(<=15th percentile)and no delay(>15th percentile). Both raw scores were used to provide 2 normative scores based on child's age in months. Higher scores indicated better language development.

  7. Change From Baseline in Total Score of Quality of Life in Childhood Epilepsy (QoLCE) Scale [ Time Frame: Baseline and Week 106 ]
    The QoLCE was a 76-item questionnaire designed specifically to measure quality of life in children with epilepsy. QOLCE consists of 16 quality of life subscales (14 multi-item and 2 single item). Each subscales had number of items or questions with responses as excellent, very good, good, fair, and poor. They were changed to 1, 2, 3, 4, and 5 as per instructions. Then changed on a scale of 100, where 1 is equal to (=) 0, 2=25, 3=50, 4=75, and 5=100. Items corresponding to each subscale were marked and there mean score was score of that subscale. The form was completed by a parent or caregiver who interacted with the child on a consistent, daily basis and took about 20 to 30 minutes to complete. The higher the score, the better the child's quality of life.

  8. Change From Baseline in Sub-scores in QoLCE [ Time Frame: Baseline and Week 106 ]
    The QoLCE was a 76-item questionnaire designed specifically to measure quality of life in children with epilepsy. QOLCE consists of 16 quality of life subscales (14 multi-item and 2 single item). Each subscales had number of items or questions with responses as excellent, very good, good, fair, and poor. They were changed to 1, 2, 3, 4, and 5 as per instructions. Then changed on a scale of 100, where 1=0, 2=25, 3=50, 4=75, and 5=100. Items corresponding to each subscale were marked and there mean score was score of that subscale. The form was completed by a parent or caregiver who interacted with the child on a consistent, daily basis and took about 20 to 30 minutes to complete. The higher the score, the better the child's quality of life.



Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 3 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion:

  1. Clinical diagnosis of LGS, which might include the presence of a slow background electroencephalogram (EEG) rhythm, slow spikes-waves pattern (less than 3 Hz), the presence of polyspikes; care should be taken not to include benign myoclonic epilepsy of infancy, atypical benign partial epilepsy (pseudo-Lennox syndrome), or continuous spike-waves of slow sleep (CSWS).
  2. On a fixed and documented dose of one to three concomitant regionally approved antiepileptic drugs (AEDs) for a minimum of 4 weeks prior to randomization with an inadequate response to treatment.
  3. Consistent seizure documentation (i.e., no uncertainty of the presence of seizures) during the pre-randomization phase.

Key Exclusion:

  1. Familial short QT syndrome
  2. Prior treatment with rufinamide within 30 days of baseline visit or discontinuation of rufinamide treatment due to safety issues related to rufinamide

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01405053


Locations
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United States, California
San Diego, California, United States, 92123
United States, Colorado
Aurora, Colorado, United States, 80045
United States, District of Columbia
Washington, District of Columbia, United States, 20010
United States, Florida
Gulf Breeze, Florida, United States, 32561
Miami, Florida, United States
Tampa, Florida, United States, 33609
Wellington, Florida, United States, 33414
United States, Georgia
Augusta, Georgia, United States, 30912
United States, Illinois
Chicago, Illinois, United States, 60637
United States, Kentucky
Lexington, Kentucky, United States, 40536
United States, Louisiana
Shreveport, Louisiana, United States, 71103
United States, New Hampshire
Lebanon, New Hampshire, United States, 03756
United States, New Jersey
Gibbsboro, New Jersey, United States, 08026
United States, New York
Rochester, New York, United States, 14642
United States, Ohio
Akron, Ohio, United States
Akson, Ohio, United States, 44308
Columbus, Ohio, United States, 43205
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Pittsburgh, Pennsylvania, United States, 15224
United States, Texas
Austin, Texas, United States, 78723
San Antonio, Texas, United States, 78258
United States, Virginia
Norfolk, Virginia, United States, 23510
Canada, Alberta
Calgary, Alberta, Canada, T2T 5C7
Edmonton, Alberta, Canada, T6G 2B7
Canada, Ontario
Toronto, Ontario, Canada, M2K 2W2
Canada
Saskatoon, Canada, S7N 0W8
France
Bron, France
Marseille, France
Paris, France
Greece
Ambelokipi Athens, Greece
Patra, Greece
Pendeli Athens, Greece
Thessaloniki, Greece
Italy
Mantua, MN, Italy
Calambrone, PI, Italy
Pisa, PI, Italy
Pavia, PV, Italy
Mantova, Italy, 46100
Roma, Italy, '00165
Salerno, Italy, 84131
Poland
Elblag, Poland
Gdansk, Poland
Kielce, Poland
Poznan, Poland
Rzeszow, Poland, 35-301
Warszawa, Poland
South Africa
Cape Town, South Africa
Sponsors and Collaborators
Eisai Inc.
Investigators
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Principal Investigator: Alexis Arzimanoglou Arzimanoglou Hopital Femme-Mere-Enfant Service D'Epilepsie -5eme etage 59 Boulevard Pinel Bron, France
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT01405053    
Other Study ID Numbers: E2080-G000-303
First Posted: July 29, 2011    Key Record Dates
Results First Posted: August 6, 2019
Last Update Posted: August 6, 2019
Last Verified: February 2016
Keywords provided by Eisai Inc.:
Central Nervous System
Additional relevant MeSH terms:
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Lennox Gastaut Syndrome
Syndrome
Disease
Pathologic Processes
Epileptic Syndromes
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Rufinamide
Anticonvulsants
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action