Lennox-Gastaut SyndromePhase 3NCT01405053

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

A Phase 3 study testing Rufinamide and Any other approved Antiepileptic Drug in people with Lennox-Gastaut Syndrome, run by Eisai Inc. at 47 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 1 year to 3 years
Conditions the study is for: Lennox-Gastaut Syndrome
What is being tested?: Rufinamide and Any other approved Antiepileptic Drug
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 37 participants
Where: 47 sitesin 7 countries
Study dates: 16 Jun 2011to 2 Nov 2015
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 1 year to 3 years
All sexes
No healthy volunteers
Child

Who may be able to join

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.

Who cannot join

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

Trial locations and contacts

47 sites in 7 countries.

Country

City, postcode or hospital

47 sites in 7 countries

United States22 sites

Study site
Akron, Ohio
Study site
Akson, Ohio, 44308
Study site
Augusta, Georgia, 30912
Study site
Aurora, Colorado, 80045
Study site
Austin, Texas, 78723
Study site
Chicago, Illinois, 60637
Study site
Columbus, Ohio, 43205
Study site
Gibbsboro, New Jersey, 08026
Study site
Gulf Breeze, Florida, 32561
Study site
Lebanon, New Hampshire, 03756
Study site
Lexington, Kentucky, 40536
Study site
Miami, Florida
Study site
Norfolk, Virginia, 23510
Study site
Philadelphia, Pennsylvania, 19104
Study site
Pittsburgh, Pennsylvania, 15224
Study site
Rochester, New York, 14642
Study site
San Antonio, Texas, 78258
Study site
San Diego, California, 92123
Study site
Shreveport, Louisiana, 71103
Study site
Tampa, Florida, 33609
Study site
Washington D.C., District of Columbia, 20010
Study site
Wellington, Florida, 33414

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Italy7 sites

Study site
Calambrone, PI
Study site
Mantua, MN
Study site
Mantua, 46100
Study site
Pavia, PV
Study site
Pisa, PI
Study site
Roma, '00165
Study site
Salerno, 84131

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Poland6 sites

Study site
Elblag
Study site
Gdansk
Study site
Kielce
Study site
Poznan
Study site
Rzeszów, 35-301
Study site
Warsaw

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Canada4 sites

Study site
Calgary, Alberta, T2T 5C7
Study site
Edmonton, Alberta, T6G 2B7
Study site
Saskatoon, S7N 0W8
Study site
Toronto, Ontario, M2K 2W2

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Greece4 sites

Study site
Ambelokipi Athens
Study site
Pátrai
Study site
Pendeli Athens
Study site
Thessaloniki

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France3 sites

Study site
Bron
Study site
Marseille
Study site
Paris

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South Africa1 site

Study site
Cape Town

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About this study

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

Conditions: Lennox-Gastaut Syndrome
Being tested: Rufinamide, Any other approved Antiepileptic Drug
Keywords: Central Nervous System
Medical subject headings: Lennox Gastaut Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

RufinamideDrug
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)
Any other approved Antiepileptic DrugDrug
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)

Study groups in NCT01405053
Study group	Role	What they receive
Rufinamide	Active comparator	Not described Receives: Drug: Rufinamide
Any other approved AED	Active comparator	Not described Receives: Drug: Any other approved Antiepileptic Drug

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 Jun 20112 Nov 2015

First posted29 Jul 2011 (estimated)
Study start16 Jun 2011
Primary completion2 Nov 2015
Study completion2 Nov 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Lennox-Gastaut SyndromeStudies of the same condition, open and under way.
More trials run by Eisai Inc.The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 37 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01405053
Sponsor's protocol ID: E2080-G000-303
Status last verified: Feb 2016
First submitted: 27 Jul 2011
Last updated: 6 Aug 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Expanded access: Available

Publications

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.
PubMed 33825230
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.
PubMed 31168494
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.
PubMed 30309816
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.
PubMed 26805435

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 3
Investigate Efficacy and Safety of Carisbamate as Adjunctive Treatment for Seizures Associated With LGS in Children and Adults
Seizures, Lennox Gastaut Syndrome
Not yet recruitingPhase 4
A Study to Investigate the Effect of Gradual Titration to Optimize Cannabidiol Treatment in Adults With LGS
Lennox-Gastaut Syndrome
Enrolling by invitationPhase 3
A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
Developmental and Epileptic Encephalopathy
RecruitingPhase 3
An Efficacy and Safety Study of Clemizole HCl in Patients With Lennox-Gastaut Syndrome
Lennox Gastaut Syndrome
Enrolling by invitation
Clinical Utility of Reduced EEG Home Monitoring in Fenfluramine Titration for Dravet and LGS
Dravet Syndrome (DS), Lennox Gastaut Syndrome (LGS)

All Lennox-Gastaut Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01405053
Acronym / sponsor ID: E2080-G000-303
Conditions: Lennox-Gastaut Syndrome
Keywords: Central Nervous System
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 37 participants (actual)
Lead sponsor: Eisai Inc.Industry (pharma, biotech, devices)
Study start: 16 Jun 2011 (actual)
Primary completion: 2 Nov 2015 (actual)
Study completion: 2 Nov 2015 (actual)
First posted: 29 Jul 2011 (estimated)
Results: Posted 6 Aug 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Rufinamide	Active comparator	Drug: Rufinamide
Any other approved AED	Active comparator	Drug: Any other approved Antiepileptic Drug

Who may qualify

Ages: 1 year to 3 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (3 listed)

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 criteria (2 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
RufinamideRufinamide 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)	Drug	Rufinamide
Any other approved Antiepileptic DrugAny 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)	Drug	Any other approved AED

Primary outcome

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.
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.

Results and safety

Results posted to the registry on 6 Aug 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Rufinamide	25	15
Any Other Approved Antiepileptic Drug	12	4

Primary outcome: 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). Mean (Standard Deviation). Unit: score on a scale

Measure	Rufinamide n = 15	Any Other Approved Antiepileptic Drug n = 4
Value	55.7 (15.81)	54.8 (4.50)

Rufinamide vs Any Other Approved Antiepileptic Drug: LS Mean difference: 2.601 (95% CI -10.5 to 15.7), p = 0.6928, ANCOVA

Population analysed: The full analysis set for primary efficacy variable included randomized participants who received rufinamide or any other approved add-on AED of the investigator's choice and had baseline and at least 1 postdose cognition measurement. Participants who were evaluable for this outcome measure at given time period were included for assessment.

Primary outcome: 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). Geometric mean (Standard Deviation). Unit: score on a scale

Measure	Rufinamide n = 24	Any Other Approved Antiepileptic Drug n = 9
Baseline	56.6 (11.27)	62.8 (13.07)
Change at Week 106	-0.3 (15.72)	-6.7 (0.58)

Adverse events

Time frame: From Visit 1 up to 30 days after the last study visit, or until resolution, whichever came first (up to approximately Week 106). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Rufinamide	10 of 25 (40%)	21 of 25 (84%)	1 of 25
Any Other Approved Antiepileptic Drug	5 of 12 (41.7%)	10 of 12 (83.3%)	0 of 12

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33825230Brigo 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.
Derived from this study: PubMed 31168494Auvin 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.
Derived from this study: PubMed 30309816Arzimanoglou 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.
Derived from this study: PubMed 26805435Arzimanoglou 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.

Related trials for Lennox-Gastaut Syndrome

RecruitingPhase 3
Investigate Efficacy and Safety of Carisbamate as Adjunctive Treatment for Seizures Associated With LGS in Children and Adults
Seizures, Lennox Gastaut Syndrome
Not yet recruitingPhase 4
A Study to Investigate the Effect of Gradual Titration to Optimize Cannabidiol Treatment in Adults With LGS
Lennox-Gastaut Syndrome
Enrolling by invitationPhase 3
A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
Developmental and Epileptic Encephalopathy
RecruitingPhase 3
An Efficacy and Safety Study of Clemizole HCl in Patients With Lennox-Gastaut Syndrome
Lennox Gastaut Syndrome
Enrolling by invitation
Clinical Utility of Reduced EEG Home Monitoring in Fenfluramine Titration for Dravet and LGS
Dravet Syndrome (DS), Lennox Gastaut Syndrome (LGS)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Alexis Arzimanoglou Arzimanoglou principal investigator

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

47 sites in 7 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Rufinamide and Any other approved Antiepileptic Drug in people with Lennox-Gastaut Syndrome, run by Eisai Inc. at 47 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 47 sites in United States, Italy, Poland, Canada, Greece and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01405053, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2019.