Clinical Trial Results:
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
Summary
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EudraCT number |
2010-023505-36 |
Trial protocol |
FR IT GR Outside EU/EEA |
Global end of trial date |
02 Nov 2015
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Results information
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Results version number |
v3(current) |
This version publication date |
28 Jul 2019
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First version publication date |
16 Jun 2016
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Other versions |
v1 , v2 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
E2080-G000-303
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01405053 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Eisai
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Sponsor organisation address |
155 Tice Boulevard, Woodcliff Lake, United States, 07677
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Public contact |
Eisai Call Center, Eisai Inc., 888 422-4743, EUMedInfo@eisai.net
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Scientific contact |
Eisai Call Center, Eisai Inc., 888 422-4743, EUMedInfo@eisai.net
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000709-PIP01-09 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
02 Nov 2015
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
02 Nov 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To compare the effect of 2 drug regimens consisting of either rufinamide or any other approved antiepileptic drug (AED) of the investigator's choice as an add-on to the subject's existing regimen of 1-3 AEDs on the overall safety and tolerability of rufinamide in subjects aged 1 to less than 4 years of age with inadequately controlled Lennox-Gastaut Syndrome (LGS). To characterize the age group specific pharmacokinetics of rufinamide in a pediatric population, 1 to less than 4 years of age, with inadequately controlled LGS, using the population approach. To evaluate the effect of rufinamide as adjunctive treatment on the cognitive development and behavioral effects in a pediatric population, 1 to less than 4 years of age, with inadequately controlled LGS.
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Protection of trial subjects |
This study was conducted in accordance with standard operating procedures (SOPs) of the sponsor (or designee), which are designed to ensure adherence to Good Clinical Practice (GCP) guidelines as required by the following:
- Principles of the World Medical Association Declaration of Helsinki (World Medical Association, 2008)
- International Conference on Harmonisation (ICH) E6 Guideline for GCP (CPMP/ICH/135/95) of the European Agency for the Evaluation of Medicinal
Products, Committee for Proprietary Medicinal Products, International Conference on Harmonisation of Pharmaceuticals for Human Use
- Title 21 of the United States (US) Code of Federal Regulations (US 21 CFR) regarding clinical studies, including Part 50 and Part 56 concerning informed subject consent and Institutional Review Board (IRB) regulations and applicable sections of US 21 CFR Part 312
- European Good Clinical Practice Directive 2005/28/EC and Clinical Trial Directive 2001/20/EC for studies conducted within any European Union (EU) country. All suspected unexpected serious adverse reactions were reported, as required, to the Competent Authorities of all involved EU member states.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
16 Jun 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Poland: 9
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Country: Number of subjects enrolled |
France: 1
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Country: Number of subjects enrolled |
Greece: 4
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Country: Number of subjects enrolled |
Italy: 6
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Country: Number of subjects enrolled |
Canada: 1
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Country: Number of subjects enrolled |
United States: 16
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Worldwide total number of subjects |
37
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EEA total number of subjects |
20
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
13
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Children (2-11 years) |
24
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Subjects took part in the study at 19 investigative sites in the United States, Canada, France, Greece, Italy, and Poland from 16 June 2011 to 02 November 2015. | ||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 43 subjects were screened, out of which 37 subjects were randomized and treated in the study. | ||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Rufinamide | ||||||||||||||||||||||||||||||
Arm description |
Subjects received rufinamide oral suspension as an add-on therapy to the subject’s existing regimen of 1 to 3 AEDs. Subjects underwent a 2 week Titration Period during which rufinamide dose was increased from 10 milligram per kilogram per day (mg/kg/day) in increments of 10 mg/kg/day every 3 days to 40 mg/kg/day and thereafter in increments of 5 mg/kg/day to the target maintenance dose of 45 mg/kg/day (all daily treatments were to be administered in 2 equally divided doses). Rufinamide dose reached at the end of the Titration period were to be maintained the same throughout the 104-week Maintenance Period. At the end of Maintenance Period, rufinamide dose should be tapered (as needed) over a period of 2 weeks. | ||||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Rufinamide
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Investigational medicinal product code |
E2080
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Other name |
Inovelon, Banzel
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Pharmaceutical forms |
Oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
Rufinamide up to 45 mg/kg/day was administered in 2 divided doses as an oral suspension (40 mg/mL).
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Arm title
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Any Other Approved Antiepileptic Drug (AED) | ||||||||||||||||||||||||||||||
Arm description |
Subjects received any other approved AED of the investigator’s choice, dosed according to the investigator’s usual practice, added to the subject’s existing regimen of 1 to 3 AEDs. At the end of Maintenance Period, the AED comparator would be discontinued according to the investigator’s usual practice. | ||||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Lamotrigine
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Investigational medicinal product code |
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Other name |
Lamictal
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Dosed according to the investigator's usual practice.
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Investigational medicinal product name |
Clobazam
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Investigational medicinal product code |
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Other name |
Onfi
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Dosed according to the investigator's usual practice.
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Investigational medicinal product name |
Topiramate
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Investigational medicinal product code |
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Other name |
Trokendi XR
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Dosed according to the investigator's usual practice.
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Investigational medicinal product name |
Phenobarbital
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Dosed according to the investigator's usual practice.
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Investigational medicinal product name |
Valproic acid
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Investigational medicinal product code |
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Other name |
Depakene, Stavzor
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Dosed according to the investigator's usual practice.
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Investigational medicinal product name |
Zonisamide
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Investigational medicinal product code |
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Other name |
Zonegran
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Dosed according to the investigator's usual practice.
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Baseline characteristics reporting groups
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Reporting group title |
Rufinamide
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Reporting group description |
Subjects received rufinamide oral suspension as an add-on therapy to the subject’s existing regimen of 1 to 3 AEDs. Subjects underwent a 2 week Titration Period during which rufinamide dose was increased from 10 milligram per kilogram per day (mg/kg/day) in increments of 10 mg/kg/day every 3 days to 40 mg/kg/day and thereafter in increments of 5 mg/kg/day to the target maintenance dose of 45 mg/kg/day (all daily treatments were to be administered in 2 equally divided doses). Rufinamide dose reached at the end of the Titration period were to be maintained the same throughout the 104-week Maintenance Period. At the end of Maintenance Period, rufinamide dose should be tapered (as needed) over a period of 2 weeks. | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Any Other Approved Antiepileptic Drug (AED)
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Reporting group description |
Subjects received any other approved AED of the investigator’s choice, dosed according to the investigator’s usual practice, added to the subject’s existing regimen of 1 to 3 AEDs. At the end of Maintenance Period, the AED comparator would be discontinued according to the investigator’s usual practice. | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Rufinamide
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Reporting group description |
Subjects received rufinamide oral suspension as an add-on therapy to the subject’s existing regimen of 1 to 3 AEDs. Subjects underwent a 2 week Titration Period during which rufinamide dose was increased from 10 milligram per kilogram per day (mg/kg/day) in increments of 10 mg/kg/day every 3 days to 40 mg/kg/day and thereafter in increments of 5 mg/kg/day to the target maintenance dose of 45 mg/kg/day (all daily treatments were to be administered in 2 equally divided doses). Rufinamide dose reached at the end of the Titration period were to be maintained the same throughout the 104-week Maintenance Period. At the end of Maintenance Period, rufinamide dose should be tapered (as needed) over a period of 2 weeks. | ||
Reporting group title |
Any Other Approved Antiepileptic Drug (AED)
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Reporting group description |
Subjects received any other approved AED of the investigator’s choice, dosed according to the investigator’s usual practice, added to the subject’s existing regimen of 1 to 3 AEDs. At the end of Maintenance Period, the AED comparator would be discontinued according to the investigator’s usual practice. |
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End point title |
Child Behavior Checklist (CBCL) Total Problem T-scores at the End of 2-year Treatment Period | ||||||||||||
End point description |
CBCL:99-item questionnaire measures specific behavioral problems/developmental delays,answered by parent/legal guardian/caregiver. Items rated on 3-point scale(0=Not True,1=Somewhat/Sometimes True,2=Very True/Often True). 99 items were combined to yield scores for 8problem area scales (emotionally reactive, anxious/depressed,somatic complaints, withdrawn,sleep,attention,aggressive behavior,and other problems) and 3summary scores (internalizing, externalizing,and total problems). Total Problem score:sum of all problem areas plus 1additional item,range from 0to198. Total raw scores are converted to t-scores with mean of 50 and standard deviation(SD) of10. T-scores were standardized test scores that indicate same degree of elevation in problems relative to normative sample of peers. Higher scores=more problems.Full analysis set(FAS):randomised subjects who received rufinamide/any other approved add-on AED of investigator’s choice,had baseline and at least 1postdose cognition measurement.
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End point type |
Primary
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End point timeframe |
End of Treatment Period (up to approximately Week 106)
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Statistical analysis title |
CBCL Total Problems Score | ||||||||||||
Statistical analysis description |
The primary statistical model for comparing the 2 treatment groups was an analysis of covariance (ANCOVA) mixed model for repeated measures with baseline score, age, and sex as covariates, and treatment, week, and treatment by week interaction as factors.
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Comparison groups |
Any Other Approved Antiepileptic Drug (AED) v Rufinamide
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Number of subjects included in analysis |
19
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.6928 [1] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
LS Mean difference | ||||||||||||
Point estimate |
2.601
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-10.5 | ||||||||||||
upper limit |
15.7 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
6.558
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Notes [1] - P-value is based on ANCOVA Least Square (LE) mean analysis for Week 106 of the study. |
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End point title |
Change From Baseline in CBCL Total Problem T-Scores at End of 2-year Treatment Period [2] | ||||||||||||||||||
End point description |
CBCL:99-item questionnaire measures specific behavioral problems/developmental delays,answered by parent/legal guardian/caregiver.Items rated on 3-point scale(0=Not True,1=Somewhat/Sometimes True,2=Very True/Often True).99 items were combined to yield scores for 8problem area scales (emotionally reactive, anxious/depressed,somaticcomplaints,withdrawn,sleep,attention,aggressive behavior,and other problems) and 3summary scores (internalizing, externalizing,and total problems). Total Problem score:sum of all problem areas plus 1additional item,range from 0to198. Total raw scores are 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=more problems.FAS:randomised subjects who received rufinamide/any other approved add-on AED of investigator’s choice,had baseline and at least 1postdose cognition measurement.‘n’:subjects evaluable at given time period.
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End point type |
Primary
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End point timeframe |
Baseline and End of Treatment Period (up to approximately Week 106)
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be analysed for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Time to Withdrawal From Treatment Due to an Adverse Event or Lack of Efficacy | ||||||||||||
End point 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. The FAS for other efficacy variable had randomized subjects who received rufinamide or any other add-on AED of the investigator’s choice and had a baseline efficacy assessment and at least 1 postbaseline efficacy assessment. Subjects who were evaluable at a given time point were included for this assessment. Lower and upper limits of 95% Confidence Interval could not be calculated since insufficient number of subjects had withdrawal from treatment due to adverse event or lack of efficacy, therefore we added -9999.0 and 99999 as space-fillers.
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End point type |
Other pre-specified
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End point timeframe |
Baseline up to the End of the Treatment Period (up to approximately Week 106)
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No statistical analyses for this end point |
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End point title |
Percent Change in Total Seizure Frequency Per 28 Days | ||||||||||||
End point 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 subject seizure diary during the specified time interval and D was equal to the number of days with non-missing data in the subject seizure diary for the specified study phase. The number of seizures was assessed and recorded by the subject’s parent(s)/caregiver(s) in the subject seizure diary. Analysis was performed on the FAS for other efficacy variable included randomized subjects who received rufinamide or any other add-on AED of the investigator’s choice and had a baseline efficacy assessment and at least 1 post baseline efficacy assessment. The FAS for other efficacy variable had randomized subjects who received rufinamide or any other add-on AED of the investigator’s choice and had a baseline efficacy assessment and at least 1 postbaseline efficacy assessment, at given time period.
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End point type |
Other pre-specified
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End point timeframe |
Baseline up to End of the Treatment Period (up to approximately Week 106)
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No statistical analyses for this end point |
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End point title |
Percent Change in Seizure Frequency by Individual Seizure Type Per 28 Days | ||||||||||||||||||||||||||||||||||||
End point 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 subject seizure diary during the specified time interval and D was equal to the number of days with non-missing data in the subject seizure diary for the specified study phase. The number of seizures was assessed and recorded by the subject’s parent(s)/caregiver(s) in the subject seizure diary. The FAS for other efficacy variable had randomized subjects who received rufinamide or any other add-on AED of the investigator’s choice and had a baseline efficacy assessment and at least 1 postbaseline efficacy assessment. Here "n" were subjects evaluable at given time period.
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End point type |
Other pre-specified
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End point timeframe |
Baseline up to End of Treatment Period (up to approximately Week 106)
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No statistical analyses for this end point |
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End point title |
Incidence of Worsening of Seizures | |||||||||||||||||||||
End point description |
Worsening of seizures was summarized by the incidence of subjects 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. Analysis was performed on the FAS for other efficacy variable included randomized subjects who received rufinamide or any other add-on AED of the investigator’s choice and had a baseline efficacy assessment and at least 1 post baseline efficacy assessment.
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End point type |
Other pre-specified
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End point timeframe |
Baseline up to End of Treatment Period (up to approximately Week 106)
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No statistical analyses for this end point |
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End point title |
Change From Baseline in CBCL Sub Scores at Week 106 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
CBCL:99-item questionnaire. Item rated on 3-point scale(0=Not True and 2=Very/Often True).99 items were combined to give scores for 8 problem area scales,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, total problems).3 summary scores reported scaled to T-scores. Total Problem score was sum of all problem areas +1 additional item, from 0 to 198. Total raw score converted to t-scores with mean of 50 and SD of 10. T-scores: standardized test scores that indicate same degree of elevation in problems relative to normative sample of peers. Higher scores=more problems. FAS: randomised subjects who received rufinamide/any other approved add-on AED of investigator’s choice, had baseline efficacy and at least 1 postbaseline efficacy assessment. ‘n’: subjects evaluable at given time period.
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End point type |
Other pre-specified
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End point timeframe |
Baseline and Week 106
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Language Development Survey (LDS) Scores During Maintenance Period | ||||||||||||||||||||||||||||||||||||||||||
End point description |
LDS:caregiver-administered survey with 8-item questionnaire and vocabulary list of 310 words organized within 14 semantic categories. List had high frequency words, less common words, and lexical chunks. Average LDS score, calculated by dividing total number of words across all valid phrases by number of phrases with greater than(>)0words; for subjects with no words, average was 0. This value was compared to standardized chart to obtain percentile rating.LDS yield 2 scores: average phrase length (number of words/phrase) and number of endorsed vocabulary words.LDS phrase length, categorized into delay (less than or equal to[<=]20th percentile); no delay(>20th percentile). LDS vocabulary, categorized into delay(<=15th percentile);no delay(>15th percentile). Both raw scores were used to provide 2normative scores based on child’s age in months. Higher score means better language development. Analysis was done on FAS for other efficacy variable."n":subjects evaluable at given time period.
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End point type |
Other pre-specified
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End point timeframe |
Baseline, Weeks 24, 56, 88, and 106
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Total Score of Quality of Life in Childhood Epilepsy (QoLCE) Scale | ||||||||||||||||||
End point description |
QoLCE: 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/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 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. Form was completed by parent or caregiver who interacted with the child on consistent, daily basis and took 20 to 30minutes to complete. The higher the score, better the child’s quality of life.FAS for other efficacy variable had randomized subjects who received rufinamide or any other add-on AED of investigator’s choice and had baseline efficacy assessment and at least 1 postbaseline efficacy assessment. Here "n" were subjects evaluable at given time period.
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End point type |
Other pre-specified
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End point timeframe |
Baseline and Week 106
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Sub-scores in QoLCE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point 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. FAS: randomized subjects who received rufinamide or any other add-on AED of the investigator’s choice and had a baseline efficacy assessment and at least 1 postbaseline efficacy assessment. Here "n" were subjects evaluable at given time period.
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End point type |
Other pre-specified
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End point timeframe |
Baseline and Week 106
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
From Visit 1 up to 30 days after the last study visit, or until resolution, whichever came first (up to approximately Week 106)
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.0
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Reporting groups
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Reporting group title |
Rufinamide
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Reporting group description |
Subjects received rufinamide 10 milligram per kilogram per day (mg/kg/day), oral suspension, followed by 10 mg/kg/day increments every 3 days to 40 mg/kg/day, and then increased by 5mg/kg/day to the target maintenance level of 45 mg/kg/day (in 2 divided doses) from Week 0 (Baseline) to Week 1 in Titration Period, further followed by, rufinamide 45 mg/kg/day, oral suspension, from Week 2 to Week 106 in Maintenance Period. Rufinamide was administered as an add-on to the subject’s existing regimen of 1-3 antiepileptic drugs (AEDs). During the Taper Period, only subjects who received rufinamide were discontinued gradually over a period of 2 weeks, as deemed necessary by the investigator. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Any other approved antiepileptic drug (AED)
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Reporting group description |
Subjects received any other approved AED of the investigator’s choice, dosed according to the investigator’s usual practice, added to the subject’s existing regimen of 1 to 3 AEDs. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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26 Oct 2011 |
Following amendment changes were made: to satisfy health authority requests, added a minimum of 25% of rufinamide-treated subjects will be between 2 and 3 years of age and that every effort will be made to include a younger population (between 1 and 3 years of age); revised exclusion for prior use of rufinamide; added blood volume required; added instructions if screening visit is extended, added duplicate, consecutive electrocardiogram (ECGs) at Visit 2 and Visits 5, 6, and 7 for steady state and maximum observed concentration (Cmax); baseline ECG prior to dosing and Visits 5, 6, and 7 approximately 4 to 6 hours after drug administration; changed qualified designated reader to central reader and additional clarification for screening ECG; added measurement of head circumference at baseline, Visits 8, 10, 13, and at Follow-up/Final Visit or early discontinuation. |
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03 Apr 2013 |
Reduced from 8 to 4 weeks the minimum required time on AEDs before randomization, and required that AED doses be documented; allowed historical seizure diaries to satisfy inclusion criteria in lieu of seizure diaries that would be compiled during the Screening Period, thus allowing the Screening Period to be shortened to expedite recruitment; changed criterion for interim analysis compilation to allow reporting of data within the time frame requested by regulators, even if fewer than 75 subjects have completed 6 months of treatment; added amylase and lipase samples to list of laboratory tests per United States Food and Drug Administration(FDA) request for subject safety. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |