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

NCT01405053 | Completed Phase 3 Results

• 1 other identifier: E2080-G000-303
• Study Type: interventional
• Target: 37
• Locations: 7 countries
• Sites: 47

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.

Conditions

Lennox-Gastaut Syndrome

Keywords

Central Nervous System

Outcome Measures

Primary Outcomes (2)

• 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were combined to yield scores for 8 problem area scales (emotionally reactive, anxious/depressed, somatic complaints, withdrawn, sleep problems, attention problems, aggressive behavior, and other problems) and 3 summary scores (internalizing, externalizing, and total problems).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.

  End of Treatment Period (up to approximately Week 106)

• 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were combined to yield scores for 8 problem area scales (emotionally reactive, anxious/depressed, somatic complaints, withdrawn, sleep problems, attention problems, aggressive behavior, and other problems) and 3 summary scores (internalizing, externalizing, and total problems).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.

  Baseline and End of Treatment Period (up to approximately Week 106)

Other Outcomes (8)

• Time to Withdrawal From Treatment Due to an Adverse Event or Lack of Efficacy

  Baseline up to the End of the Treatment Period (up to approximately Week 106)

• Percent Change in Total Seizure Frequency Per 28 Days

  Baseline up to End of the Treatment Period (up to approximately Week 106)

• Percent Change in Seizure Frequency by Individual Seizure Type Per 28 Days

  Baseline up to End of Treatment Period (up to approximately Week 106)

Study Arms (2)

Rufinamide

ACTIVE COMPARATOR

Drug: Rufinamide

Any other approved AED

ACTIVE COMPARATOR

Drug: Any other approved Antiepileptic Drug

Interventions

Rufinamide DRUG

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)

Rufinamide

Any other approved Antiepileptic Drug 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)

Any other approved AED

Eligibility Criteria

• Age: 1 Year - 3 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (47)

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San Diego, California, 92123, United States

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Aurora, Colorado, 80045, United States

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Washington D.C., District of Columbia, 20010, United States

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Gulf Breeze, Florida, 32561, United States

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Miami, Florida, United States

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Tampa, Florida, 33609, United States

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Wellington, Florida, 33414, United States

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Augusta, Georgia, 30912, United States

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Chicago, Illinois, 60637, United States

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Lexington, Kentucky, 40536, United States

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Shreveport, Louisiana, 71103, United States

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Lebanon, New Hampshire, 03756, United States

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Gibbsboro, New Jersey, 08026, United States

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Rochester, New York, 14642, United States

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Akron, Ohio, United States

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Akson, Ohio, 44308, United States

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Columbus, Ohio, 43205, United States

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Philadelphia, Pennsylvania, 19104, United States

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Pittsburgh, Pennsylvania, 15224, United States

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Austin, Texas, 78723, United States

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San Antonio, Texas, 78258, United States

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Norfolk, Virginia, 23510, United States

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Calgary, Alberta, T2T 5C7, Canada

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Edmonton, Alberta, T6G 2B7, Canada

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Toronto, Ontario, M2K 2W2, Canada

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Saskatoon, S7N 0W8, Canada

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Bron, France

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Marseille, France

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Paris, France

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Ambelokipi Athens, Greece

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Pátrai, Greece

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Pendeli Athens, Greece

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Thessaloniki, Greece

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Mantova, MN, Italy

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Calambrone, PI, Italy

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Pisa, PI, Italy

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Pavia, PV, Italy

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Mantova, 46100, Italy

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Roma, '00165, Italy

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Salerno, 84131, Italy

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Elblag, Poland

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Gdansk, Poland

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Kielce, Poland

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Poznan, Poland

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Rzeszów, 35-301, Poland

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Warsaw, Poland

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Cape Town, South Africa

Location

Related Publications (4)

• 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.

  PMID: 33825230 DERIVED

• 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.

  PMID: 31168494 DERIVED

• 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.

  PMID: 30309816 DERIVED

• 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.

  PMID: 26805435 DERIVED

MeSH Terms

Conditions

Lennox Gastaut Syndrome

Interventions

rufinamide

Condition Hierarchy (Ancestors)

Epileptic Syndromes; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Eisai Medical Services
• Organization: Eisai Inc.

esi_medinfo@eisai.com

1-888-422-4743

Study Officials

• Alexis Arzimanoglou Arzimanoglou

  Hopital Femme-Mere-Enfant Service D'Epilepsie -5eme etage 59 Boulevard Pinel Bron, France

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: July 27, 2011
• First Posted: July 29, 2011
• Study Start: June 16, 2011
• Primary Completion: November 2, 2015
• Study Completion: November 2, 2015
• Last Updated: August 6, 2019
• Results First Posted: August 6, 2019

Record last verified: 2016-02

Locations

GR (4); IT (7); US (22); FR (3); ZA (1); CA (4); PL (6)