Lennox-Gastaut SyndromePhase 3NCT01146951

A Placebo-Controlled, Double-Blind Comparative Study of E2080 in Lennox-Gastaut Syndrome Patients (Study E2080-J081-304)

A Phase 3 study testing Rufinamide (E2080) in people with Lennox-Gastaut Syndrome, run by Eisai Limited at 23 sites in Japan.

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

To confirm that the combination therapy of rufinamide has superior efficacy compared to placebo in patients with Lennox-Gastaut syndrome. Read more about this study

Who is it for?: Ages 4 to 30 years
Conditions the study is for: Lennox-Gastaut Syndrome
What is being tested?: Rufinamide (E2080)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 66 participants
Where: 23 sitesJapan
Study dates: Jun 2010to Aug 2011
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 4 to 30 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

Participants who are diagnosed as Lennox-Gastaut syndrome with tonic/atonic seizures and atypical absence seizures (A history of atypical absence seizures will also be incorporated).
Participants who had a slow spike-and-wave pattern in an electroencephalogram within 6 months prior to the enrollment for the Observation Period.
Participants who had at least a total of 90 seizures in the 28 days prior to the enrollment for the Observation Period.
Participants who have been on 1 - 3 anti-epileptic drugs from 28 days prior to the enrollment for the Observation Period and have not changed the type of the anti-epileptic drugs.
Participants who have not changed the type nor the dose or administration of the anti-epileptic drugs they are taking in the Observation Period.

Who cannot join

Participants who had a history of generalized tonic-clonic status epilepticus within baseline.
Participants who received drug therapy at least 4 times to be rescued from status epilepticus within baseline.
Participants who had a history of hypoxia which needed emergency resuscitation within 12 months prior to the Treatment Period.
Participants who were on a ketogenic diet or have received adrenocorticotropic hormone (ACTH) therapy or Vitamin B6 therapy within 6 months prior to the Treatment Period.
Participants who had a history of suicide attempt within the 1 year prior to the Treatment Period.
Participants who had a history of or has an allergy to triazole compound.
Participants who have clinically significant electrocardiogram abnormalities at baseline.
Participants who are pregnant, who may be pregnant, who are lactating or who wish to be pregnant.

Trial locations and contacts

23 sites in 1 country.

City, postcode or hospital

23 sites in 1 country

Japan23 sites

Study site
Fukuoka, Fukuoka
Study site
Goshi-shi, Kumamoto
Study site
Hiroshima, Hiroshima
Study site
Iwamuma-shi, Miyagi
Study site
Kobe, Hyōgo
Study site
Kodaira-shi, Tokyo
Study site
Kokubunji-shi, Tokyo
Study site
Matsuyama, Ehime
Study site
Moriya-shi, Shiga
Study site
Nagoya, Aichi-ken
Study site
Nara, Nara
Study site
Neyagawa, Osaka
Study site
Niigata, Niigata
Study site
Okayama, Okayama-ken
Study site
Omura-shi, Nagasaki
Study site
Osaka, Osaka
Study site
Sapporo, Hokkaido
Study site
Shinjuku-ku, Tokyo
Study site
Shizuoka, Shizuoka
Study site
Suita-shi, Osaka
Study site
Toyoma-shi, Toyama
Study site
Yokohama, Kanagawa
Study site
Yufu-shi, Oita Prefecture

Other trials in Japan

About this study

Official title: A Placebo-Controlled, Double-Blind Comparative Study of E2080 in Lennox-Gastaut Syndrome Patients

To confirm that the combination therapy of rufinamide has superior efficacy compared to placebo in patients with Lennox-Gastaut syndrome.

Conditions: Lennox-Gastaut Syndrome
Being tested: Rufinamide (E2080), Placebo
Keywords: Epilepsy, Seizures
Medical subject headings: Lennox Gastaut Syndrome, Epilepsy, Seizures

What participants receive

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

Rufinamide (E2080)Drug
Also called E2080
Rufinamide tablets administered orally twice daily after breakfast and dinner. Treatment was divided into a Dose Titration Period (2 weeks) and a Dose Maintenance Period (10 weeks). As a general rule, the dose was increased by 1 step every 2 days until it reached the target maintenance dose determined by body weight at the start of the Observation Period.
Target maintenance dose:
15.0 - 30.0 kg: 1000 mg/day (5 tablets each in the morning and evening) 30.1 - 50.0 kg: 1800 mg/day (4 tablets in the morning and 5 in the evening) 50.1 - 70.0 kg: 2400 mg/day (6 tablets each in the morning and evening) >= 70.1 kg: 3200 mg/day (8 tablets each in the morning and evening)
PlaceboDrug
Rufinamide Matching Placebo tablets administered orally twice daily after breakfast and dinner for a total of 12 weeks.

Study groups in NCT01146951
Study group	Role	What they receive
Rufinamide (E2080)	Experimental	Not described Receives: Drug: Rufinamide (E2080)
Placebo	Placebo comparator	Not described Receives: Drug: Placebo

What is being measured

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

Percent Change in Tonic-Atonic Seizure Frequency From Baseline (Per 28 Days)
The sum of the frequencies of tonic seizures and atonic seizures was defined as the "tonic-atonic seizure frequency" and the percent change in tonic-atonic seizure frequency per 28 days was assessed. The percent change in tonic-atonic seizure frequency was calculated using the tonic-atonic seizure frequency per 28 days of the Observation Period as the baseline and the tonic-atonic seizure frequency per 28 days of the Treatment Period as the post-treatment value. Percentage change in tonic - atonic seizure frequency was calculated as follows: [100 x (post-treatment value - baseline)/ baseline].
The frequency of epileptic seizures was recorded in the seizure diary by the recorder. Seizure frequency was counted based on the classification established by the International League Against Epilepsy (ILAE). The diary recorder monitored the participant and recorded the seizure diary in a consistent manner, and continued these practices throughout the study period.
Measured: Baseline (28 day observational period) and End of Treatment (28 day treatment period)

Secondary outcomes (4)

Number of Participants Achieving a 50% Reduction in Tonic-atonic Seizure Frequency
50% Responder Rate in Tonic-Atonic Seizure Frequency was presented as the number of participants who achieved a 50% reduction in tonic-atonic seizure frequency.
Measured: 12 weeks
Percent Change in Total Seizure Frequency (Per 28 Days)
Percent change in the total seizure frequency (per 28 days) was calculated using the total seizure frequency per 28 days of the Observation Period as the baseline and the total seizure frequency per 28 days of the Treatment Period as the post-treatment value. Percentage change in total seizure frequency was calculated as follows: [100 x (post-treatment value - baseline)/ baseline].
Measured: Baseline (28 day observational period) and End of Treatment (28 day treatment period)
Percentage Change in the Frequency of Seizures Other Than Tonic-atonic Seizures (Per 28 Days)
Percent change in the frequency of seizures other than tonic-atonic seizures (per 28 days) was calculated using the total seizure frequency per 28 days of the Observation Period as the baseline and the total seizure frequency per 28 days of the Treatment Period as the post-treatment value. Percentage change in total seizure frequency was calculated as follows: [100 x (post-treatment value - baseline)/ baseline].
Seizures analyzed other than tonic-atonic seizures included:
Partial seizure freq. (frequency), Absence seizure, Atyp. (atypical) absence seizure, Myoclonic seizure, Clonic seizure, Tonic seizure, Tonic-clonic seizure, Atonic seizure, \& Uncla. (unclassified) epileptic seizure.
The frequency of epileptic seizures was recorded in the diary by the recorder. Seizure frequency was counted based on the classification established by the International League Against Epilepsy (ILAE). The diary recorder monitored the participant and recorded the seizure diary in a consistent manner.
Measured: Baseline (28 day observational period) and End of Treatment (28 day treatment period)
Clinical Global Impression of Change (CGIC)
CGIC in participants with Lennox-Gastaut Syndrome (LGS) relative to placebo was presented as number of participants in each category at the final assessment (last observation carried forward [LOCF]) \& at Week 12 of the Treatment Period. The investigator assessed the CGIC by comparing the participants' condition during the 4 weeks immediately before the completion (or discontinuation [d/c]) of the Treatment Period to his/her condition during the 4-week Observation Period (for participants who d/c'd the study during the Treatment Period, the CGIC was assessed by comparing the participant's condition from the start to discontinuation of the study treatment to his/her condition during the 4-week Observation Period).
The CGIC was assessed according to the following 7-grade scale based on the frequency \& severity of seizures, AEs, and overall conditions of daily life.
Markedly improved, Improved, Slightly improved, Unchanged, Slightly worsened, Worsened, Markedly worsened.
Measured: Up to Week 12 of the treatment period

Timeline

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

Jun 2010Aug 2011

First posted22 Jun 2010 (estimated)
Study startJun 2010
Primary completionAug 2011
Study completionAug 2011

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 (2)Papers the sponsor has linked to this study.
Other trials for Lennox-Gastaut SyndromeStudies of the same condition, open and under way.
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: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 66 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01146951
Sponsor's protocol ID: E2080-J081-304
Status last verified: Jan 2018
First submitted: 14 Jun 2010
Last updated: 24 Jan 2018
Results posted: Yes, on ClinicalTrials.gov

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
Panebianco M, Prabhakar H, Marson AG. Rufinamide add-on therapy for drug-resistant epilepsy. Cochrane Database Syst Rev. 2020 Nov 8;11(11):CD011772. doi: 10.1002/14651858.CD011772.pub3.
PubMed 33179247

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

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)
Not yet recruiting
Sleep-Driven Adaptive Neuromodulation in Lennox-Gastaut Syndrome
Lennox Gastaut Syndrome (LGS), Epilepsy

All Lennox-Gastaut Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Placebo-Controlled, Double-Blind Comparative Study of E2080 in Lennox-Gastaut Syndrome Patients
ClinicalTrials.gov ID: NCT01146951
Acronym / sponsor ID: E2080-J081-304
Conditions: Lennox-Gastaut Syndrome
Keywords: Epilepsy, Seizures
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 66 participants (actual)
Lead sponsor: Eisai LimitedIndustry (pharma, biotech, devices)
Study start: Jun 2010
Primary completion: Aug 2011 (actual)
Study completion: Aug 2011 (actual)
First posted: 22 Jun 2010 (estimated)
Results: Posted 21 Nov 2013

Clinical summary

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

To confirm that the combination therapy of rufinamide has superior efficacy compared to placebo in patients with Lennox-Gastaut syndrome.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Rufinamide (E2080)	Experimental	Drug: Rufinamide (E2080)
Placebo	Placebo comparator	Drug: Placebo

Who may qualify

Ages: 4 to 30 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (5 listed)

Participants who are diagnosed as Lennox-Gastaut syndrome with tonic/atonic seizures and atypical absence seizures (A history of atypical absence seizures will also be incorporated).
Participants who had a slow spike-and-wave pattern in an electroencephalogram within 6 months prior to the enrollment for the Observation Period.
Participants who had at least a total of 90 seizures in the 28 days prior to the enrollment for the Observation Period.
Participants who have been on 1 - 3 anti-epileptic drugs from 28 days prior to the enrollment for the Observation Period and have not changed the type of the anti-epileptic drugs.
Participants who have not changed the type nor the dose or administration of the anti-epileptic drugs they are taking in the Observation Period.

Key exclusion criteria (8 listed)

Participants who had a history of generalized tonic-clonic status epilepticus within baseline.
Participants who received drug therapy at least 4 times to be rescued from status epilepticus within baseline.
Participants who had a history of hypoxia which needed emergency resuscitation within 12 months prior to the Treatment Period.
Participants who were on a ketogenic diet or have received adrenocorticotropic hormone (ACTH) therapy or Vitamin B6 therapy within 6 months prior to the Treatment Period.
Participants who had a history of suicide attempt within the 1 year prior to the Treatment Period.

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
Rufinamide (E2080)Also: E2080Rufinamide tablets administered orally twice daily after breakfast and dinner. Treatment was divided into a Dose Titration Period (2 weeks) and a Dose Maintenance Period (10 weeks). As a general rule, the dose was increased by 1 step every 2 days until it reached the target maintenance dose determined by body weight at the start of the Observation Period. Target maintenance dose: 15.0 - 30.0 kg: 1000 mg/day (5 tablets each in the morning and evening) 30.1 - 50.0 kg: 1800 mg/day (4 tablets in the morning and 5 in the evening) 50.1 - 70.0 kg: 2400 mg/day (6 tablets each in the morning and evening) >= 70.1 kg: 3200 mg/day (8 tablets each in the morning and evening)	Drug	Rufinamide (E2080)
PlaceboRufinamide Matching Placebo tablets administered orally twice daily after breakfast and dinner for a total of 12 weeks.	Drug	Placebo

Primary outcome

Percent Change in Tonic-Atonic Seizure Frequency From Baseline (Per 28 Days)
Time frame: Baseline (28 day observational period) and End of Treatment (28 day treatment period)
The sum of the frequencies of tonic seizures and atonic seizures was defined as the "tonic-atonic seizure frequency" and the percent change in tonic-atonic seizure frequency per 28 days was assessed. The percent change in tonic-atonic seizure frequency was calculated using the tonic-atonic seizure frequency per 28 days of the Observation Period as the baseline and the tonic-atonic seizure frequency per 28 days of the Treatment Period as the post-treatment value. Percentage change in tonic - atonic seizure frequency was calculated as follows: [100 x (post-treatment value - baseline)/ baseline]. The frequency of epileptic seizures was recorded in the seizure diary by the recorder. Seizure frequency was counted based on the classification established by the International League Against Epilepsy (ILAE). The diary recorder monitored the participant and recorded the seizure diary in a consistent manner, and continued these practices throughout the study period.

4 secondary outcomes

Number of Participants Achieving a 50% Reduction in Tonic-atonic Seizure Frequency
Time frame: 12 weeks
Percent Change in Total Seizure Frequency (Per 28 Days)
Time frame: Baseline (28 day observational period) and End of Treatment (28 day treatment period)
Percentage Change in the Frequency of Seizures Other Than Tonic-atonic Seizures (Per 28 Days)
Time frame: Baseline (28 day observational period) and End of Treatment (28 day treatment period)
Clinical Global Impression of Change (CGIC)
Time frame: Up to Week 12 of the treatment period

Results and safety

Results posted to the registry on 21 Nov 2013, 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 (E2080)	29	25
Placebo	30	29

Primary outcome: Percent Change in Tonic-Atonic Seizure Frequency From Baseline (Per 28 Days)

Time frame: Baseline (28 day observational period) and End of Treatment (28 day treatment period). Median (Full Range). Unit: Percent Change

Measure	Rufinamide (E2080) n = 28	Placebo n = 30
Value	-24.20 (-93.5 to 27.2)	-3.25 (-81.6 to 151.9)

Rufinamide (E2080) vs Placebo: Hodges-Lehmann: -26.65 (90% CI -40.30 to -11.80), p = 0.003, Wilcoxon (Mann-Whitney)

Population analysed: Full analysis set (FAS) is defined as participants who were registered for the Treatment Period and excludes those listed below. Participants who did not meet the inclusion criterion related the target disease, participants who did not take the study drug, participants without any evaluable efficacy data after the start of study treatment.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: From date of first dose until date of last dose of study treatment, up to approximately 1 year 2 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Rufinamide (E2080)	1 of 29 (3.4%)	27 of 29 (93.1%)	Not reported
Placebo	1 of 30 (3.3%)	21 of 30 (70%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2018.
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 33179247Panebianco M, Prabhakar H, Marson AG. Rufinamide add-on therapy for drug-resistant epilepsy. Cochrane Database Syst Rev. 2020 Nov 8;11(11):CD011772. doi: 10.1002/14651858.CD011772.pub3.

Related trials for 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)
Not yet recruiting
Sleep-Driven Adaptive Neuromodulation in Lennox-Gastaut Syndrome
Lennox Gastaut Syndrome (LGS), Epilepsy

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.

Hiroki Takano study director

Neuroscience Clinical Development Section. JAC PCU. Eisai Co., Ltd.

23 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Rufinamide (E2080) in people with Lennox-Gastaut Syndrome, run by Eisai Limited at 23 sites in Japan.

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 5 inclusion and 8 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 24 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in Japan. 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. Some participants in this study may receive a placebo. 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 21 Nov 2013). 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?

Percent Change in Tonic-Atonic Seizure Frequency From Baseline (Per 28 Days) (time frame: Baseline (28 day observational period) and End of Treatment (28 day treatment period)). 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 NCT01146951, which also lists 2 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 24 Jan 2018.