Clinical trial NCT01405053: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lennox-Gastaut Syndrome
Keywords: Central Nervous System
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2011-07-29
Enrollment: 37
Sex: ALL
Minimum age (years): 1
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Child Behavior Checklist (CBCL) Total Problem T-scores at the End of 2-year Treatment Period
timeFrame: End of Treatment Period (up to approximately Week 106)
measure: Change From Baseline in CBCL Total Problem T-Scores at End of 2-year Treatment Period
timeFrame: Baseline and End of Treatment Period (up to approximately Week 106)
Secondary outcomes:
Other outcomes:
measure: Time to Withdrawal From Treatment Due to an Adverse Event or Lack of Efficacy
timeFrame: Baseline up to the End of the Treatment Period (up to approximately Week 106)
measure: Percent Change in Total Seizure Frequency Per 28 Days
timeFrame: Baseline up to End of the Treatment Period (up to approximately Week 106)
measure: Percent Change in Seizure Frequency by Individual Seizure Type Per 28 Days
timeFrame: Baseline up to End of Treatment Period (up to approximately Week 106)
measure: Incidence of Worsening of Seizures
timeFrame: Baseline up to End of Treatment Period (up to approximately Week 106)
measure: Change From Baseline in CBCL Sub Scores at Week 106
timeFrame: Baseline and Week 106
measure: Change From Baseline in Language Development Survey (LDS) Scores During Maintenance Period
timeFrame: Baseline, Weeks 24, 56, 88, and 106
measure: Change From Baseline in Total Score of Quality of Life in Childhood Epilepsy (QoLCE) Scale
timeFrame: Baseline and Week 106
measure: Change From Baseline in Sub-scores in QoLCE
timeFrame: Baseline and Week 106
Locations:
city: San Diego
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Washington
country: United States
state: District of Columbia
city: Gulf Breeze
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Wellington
country: United States
state: Florida
city: Augusta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Lexington
country: United States
state: Kentucky
city: Shreveport
country: United States
state: Louisiana
city: Lebanon
country: United States
state: New Hampshire
city: Gibbsboro
country: United States
state: New Jersey
city: Rochester
country: United States
state: New York
city: Akron
country: United States
state: Ohio
city: Akson
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Austin
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Norfolk
country: United States
state: Virginia
city: Calgary
country: Canada
state: Alberta
city: Edmonton
country: Canada
state: Alberta
city: Toronto
country: Canada
state: Ontario
city: Saskatoon
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
country: Italy
state: MN
city: Calambrone
country: Italy
state: PI
city: Pisa
country: Italy
state: PI
city: Pavia
country: Italy
state: PV
city: Mantova
country: Italy
city: Roma
country: Italy
city: Salerno
country: Italy
city: Elblag
country: Poland
city: Gdansk
country: Poland
city: Kielce
country: Poland
city: Poznan
country: Poland
city: Rzeszow
country: Poland
city: Warszawa
country: Poland
city: Cape Town
country: South Africa
Study officials:
affiliation: Hopital Femme-Mere-Enfant Service D'Epilepsie -5eme etage 59 Boulevard Pinel Bron, France
name: Alexis Arzimanoglou Arzimanoglou
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.