Back to resultsStudy of Rufinamide in Pediatric Subjects 1 to Less Than 4 Years of Age With Lennox-Gastaut Syndrome Inadequately Controlled With Other Anti-epileptic Drugs
Primary Purpose
Lennox-Gastaut Syndrome
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Rufinamide
Any other approved Antiepileptic Drug
Sponsored by
About this trial
This is an interventional treatment trial for Lennox-Gastaut Syndrome focused on measuring Central Nervous System
Eligibility Criteria
Key Inclusion:
- 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).
- 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.
- Consistent seizure documentation (i.e., no uncertainty of the presence of seizures) during the pre-randomization phase.
Key Exclusion:
- Familial short QT syndrome
- Prior treatment with rufinamide within 30 days of baseline visit or discontinuation of rufinamide treatment due to safety issues related to rufinamide
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Rufinamide
Any other approved AED
Arm Description
Outcomes
Primary Outcome Measures
Child Behavior Checklist (CBCL) Total Problem T-scores at the End of 2-year Treatment Period
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were combined to yield scores for 8 problem area scales (emotionally reactive, anxious/depressed, somatic complaints, withdrawn, sleep problems, attention problems, aggressive behavior, and other problems) and 3 summary scores (internalizing, externalizing, and total problems).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.
Change From Baseline in CBCL Total Problem T-Scores at End of 2-year Treatment Period
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.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01405053
Brief Title
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
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
June 16, 2011 (Actual)
Primary Completion Date
November 2, 2015 (Actual)
Study Completion Date
November 2, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eisai Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lennox-Gastaut Syndrome
Keywords
Central Nervous System
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
37 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rufinamide
Arm Type
Active Comparator
Arm Title
Any other approved AED
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Rufinamide
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Any other approved Antiepileptic Drug
Intervention Description
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 Measure Information:
Title
Child Behavior Checklist (CBCL) Total Problem T-scores at the End of 2-year Treatment Period
Description
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.
Time Frame
End of Treatment Period (up to approximately Week 106)
Title
Change From Baseline in CBCL Total Problem T-Scores at End of 2-year Treatment Period
Description
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.
Time Frame
Baseline and End of Treatment Period (up to approximately Week 106)
Other Pre-specified Outcome Measures:
Title
Time to Withdrawal From Treatment Due to an Adverse Event or Lack of Efficacy
Description
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.
Time Frame
Baseline up to the End of the Treatment Period (up to approximately Week 106)
Title
Percent Change in Total Seizure Frequency Per 28 Days
Description
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.
Time Frame
Baseline up to End of the Treatment Period (up to approximately Week 106)
Title
Percent Change in Seizure Frequency by Individual Seizure Type Per 28 Days
Description
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.
Time Frame
Baseline up to End of Treatment Period (up to approximately Week 106)
Title
Incidence of Worsening of Seizures
Description
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.
Time Frame
Baseline up to End of Treatment Period (up to approximately Week 106)
Title
Change From Baseline in CBCL Sub Scores at Week 106
Description
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.
Time Frame
Baseline and Week 106
Title
Change From Baseline in Language Development Survey (LDS) Scores During Maintenance Period
Description
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.
Time Frame
Baseline, Weeks 24, 56, 88, and 106
Title
Change From Baseline in Total Score of Quality of Life in Childhood Epilepsy (QoLCE) Scale
Description
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.
Time Frame
Baseline and Week 106
Title
Change From Baseline in Sub-scores in QoLCE
Description
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.
Time Frame
Baseline and Week 106
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
3 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion:
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).
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.
Consistent seizure documentation (i.e., no uncertainty of the presence of seizures) during the pre-randomization phase.
Key Exclusion:
Familial short QT syndrome
Prior treatment with rufinamide within 30 days of baseline visit or discontinuation of rufinamide treatment due to safety issues related to rufinamide
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alexis Arzimanoglou Arzimanoglou
Organizational Affiliation
Hopital Femme-Mere-Enfant Service D'Epilepsie -5eme etage 59 Boulevard Pinel Bron, France
Official's Role
Principal Investigator
Facility Information:
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
City
Gulf Breeze
State/Province
Florida
ZIP/Postal Code
32561
Country
United States
City
Miami
State/Province
Florida
Country
United States
City
Tampa
State/Province
Florida
ZIP/Postal Code
33609
Country
United States
City
Wellington
State/Province
Florida
ZIP/Postal Code
33414
Country
United States
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71103
Country
United States
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
City
Gibbsboro
State/Province
New Jersey
ZIP/Postal Code
08026
Country
United States
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
City
Akron
State/Province
Ohio
Country
United States
City
Akson
State/Province
Ohio
ZIP/Postal Code
44308
Country
United States
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
City
Austin
State/Province
Texas
ZIP/Postal Code
78723
Country
United States
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78258
Country
United States
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23510
Country
United States
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2T 5C7
Country
Canada
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2B7
Country
Canada
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M2K 2W2
Country
Canada
City
Saskatoon
ZIP/Postal Code
S7N 0W8
Country
Canada
City
Bron
Country
France
City
Marseille
Country
France
City
Paris
Country
France
City
Ambelokipi Athens
Country
Greece
City
Patra
Country
Greece
City
Pendeli Athens
Country
Greece
City
Thessaloniki
Country
Greece
City
Mantua
State/Province
MN
Country
Italy
City
Calambrone
State/Province
PI
Country
Italy
City
Pisa
State/Province
PI
Country
Italy
City
Pavia
State/Province
PV
Country
Italy
City
Mantova
ZIP/Postal Code
46100
Country
Italy
City
Roma
ZIP/Postal Code
'00165
Country
Italy
City
Salerno
ZIP/Postal Code
84131
Country
Italy
City
Elblag
Country
Poland
City
Gdansk
Country
Poland
City
Kielce
Country
Poland
City
Poznan
Country
Poland
City
Rzeszow
ZIP/Postal Code
35-301
Country
Poland
City
Warszawa
Country
Poland
City
Cape Town
Country
South Africa
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
31168494
Citation
Auvin S, Williams B, McMurray R, Kumar D, Perdomo C, Malhotra M. Novel seizure outcomes in patients with Lennox-Gastaut syndrome: Post hoc analysis of seizure-free days in rufinamide Study 303. Epilepsia Open. 2019 Mar 13;4(2):275-280. doi: 10.1002/epi4.12314. eCollection 2019 Jun.
Results Reference
derived
PubMed Identifier
30309816
Citation
Arzimanoglou A, Ferreira J, Satlin A, Olhaye O, Kumar D, Dhadda S, Bibbiani F. Evaluation of long-term safety, tolerability, and behavioral outcomes with adjunctive rufinamide in pediatric patients (>/=1 to <4 years old) with Lennox-Gastaut syndrome: Final results from randomized study 303. Eur J Paediatr Neurol. 2019 Jan;23(1):126-135. doi: 10.1016/j.ejpn.2018.09.010. Epub 2018 Sep 27.
Results Reference
derived
PubMed Identifier
26805435
Citation
Arzimanoglou A, Ferreira JA, Satlin A, Mendes S, Williams B, Critchley D, Schuck E, Hussein Z, Kumar D, Dhadda S, Bibbiani F. Safety and pharmacokinetic profile of rufinamide in pediatric patients aged less than 4 years with Lennox-Gastaut syndrome: An interim analysis from a multicenter, randomized, active-controlled, open-label study. Eur J Paediatr Neurol. 2016 May;20(3):393-402. doi: 10.1016/j.ejpn.2015.12.015. Epub 2016 Jan 11.
Results Reference
derived
Learn more about this trial
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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