Lemborexant for Epilepsy

(L'ÉTOILE Trial)

Recruiting at 1 trial location

Overseen By Marcus C Ng, MD, FRCPC

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Manitoba

Must not be taking: Antiseizure, Concomitant

Disqualifiers: Hepatic impairment, Respiratory issues, Psychiatric disorders, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5 weeks

26 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if Lemborexant, a medication, can improve sleep for people with epilepsy. Researchers are comparing Lemborexant to a placebo, a pill with no active ingredient, to assess its impact on sleep quality. The trial includes two groups: one takes Lemborexant first, and the other takes the placebo first. This trial may suit individuals with focal epilepsy who experience sleep difficulties and have not recently changed their seizure medications. As a Phase 3 trial, it represents the final step before FDA approval, allowing participants to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot change your antiseizure medication for at least one month before and during the study. Also, certain other medications might not be allowed, as per the SUNRISE1 guidelines.

Is there any evidence suggesting that Lemborexant is likely to be safe for humans?

Research has shown that lemborexant is generally safe for people. In earlier studies with over 3,000 participants, lemborexant was well-tolerated, meaning most did not experience serious side effects. These studies also support its use for treating insomnia, a sleep disorder.

Since this trial is in a late stage, lemborexant has already undergone testing in earlier phases, suggesting it is likely to be well-tolerated by most people. However, each person's experience may differ. Participants should discuss possible side effects with the study team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for epilepsy?

Researchers are excited about lemborexant for epilepsy because it targets the orexin system, which is a new approach compared to traditional epilepsy medications that often focus on sodium channels or GABA receptors. Lemborexant, originally used for insomnia, has a different mechanism of action that might help control seizures by regulating sleep-wake cycles, potentially offering benefits to patients who haven't had success with existing treatments like valproate, lamotrigine, or levetiracetam. Additionally, lemborexant's nightly dosing could simplify treatment regimens, enhancing patient compliance and quality of life.

What evidence suggests that Lemborexant might be an effective treatment for epilepsy?

Research has shown that Lemborexant can help people with insomnia sleep better. In one study, participants who took Lemborexant fell asleep faster and stayed asleep longer than those who took a placebo, a pill with no active medicine. The study found this treatment safe for long-term use. Lemborexant improves sleep quality by blocking certain brain signals that keep people awake. Although approved for treating insomnia, this trial will investigate whether Lemborexant can help with sleep problems in people with epilepsy. Participants will receive either Lemborexant or a placebo to evaluate its effectiveness in this new context. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This clinical trial is for individuals who have sleep-related focal epilepsy and are willing to use contraception. It's not specified, but typically participants would need to be in good general health aside from their epilepsy and insomnia.

Inclusion Criteria

I have epilepsy that occurs during sleep.

I am using birth control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Lemborexant or placebo to assess improvement in sleep for patients with epilepsy

5 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lemborexant

Trial Overview The trial is testing Lemborexant, a potential treatment for insomnia in people with epilepsy. Participants will either receive Lemborexant or a placebo (a pill without any active drug) to see if there's an improvement in sleep.

How Is the Trial Designed?

Group I: Investigational Product First Active Control 2 Interventions

10mg qhs

Group II: Placebo First Placebo Group 2 Interventions

0mg

Lemborexant is already approved in United States, Canada, Japan for the following indications:

Approved in United States as Dayvigo for:

• Insomnia characterized by difficulties with sleep onset and/or sleep maintenance in adults

Approved in Canada as Dayvigo for:

• Insomnia characterized by difficulties with sleep onset and/or sleep maintenance, with or without associated impairment in daily functioning

Approved in Japan as Dayvigo for:

• Treatment of insomnia

Who Is Running the Clinical Trial?

University of Manitoba

Lead Sponsor

Trials

628

Recruited

209,000+

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

Published Research Related to This Trial

In a study of 73 patients with Lennox-Gastaut syndrome, felbamate treatment resulted in a 34% reduction in atonic seizures and a 19% decrease in total seizure frequency, compared to a placebo group that experienced a 9% decrease and a 4% increase, respectively.

Felbamate was associated with improved quality of life evaluations from parents or guardians, and while it did not significantly reduce seizures during video monitoring, it did lead to a notable decrease in tonic-clonic seizures, indicating its potential efficacy in managing this complex condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of felbamate in childhood epileptic encephalopathy (Lennox-Gastaut syndrome). [2018]

A teenage female patient ingested eight times the maximum dose of felbamate in a suicide gesture but only experienced mild side effects, suggesting a relatively high safety margin for the drug in overdose situations.

Felbamate, approved for treating partial seizures and Lennox-Gastaut syndrome, is effective and has a manageable side effect profile, making it a viable option in epilepsy treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Felbamate overdose: a case report and discussion of a new antiepileptic drug. Nagel, TR., Schunk, JE.[2019]

Felbamate (FBM) significantly reduced the total number of seizures by 26% in patients with therapy refractory Lennox-Gastaut syndrome, compared to a 5% increase in the placebo group, indicating its efficacy as an antiepileptic drug.

Approximately 50% of patients taking FBM experienced at least a 50% reduction in seizure frequency, and the drug was generally well tolerated, with mild side effects like gastrointestinal symptoms and somnolence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Felbamate in the treatment of Lennox-Gastaut syndrome. Jensen, PK.[2019]

In a retrospective case series of six dogs with idiopathic/genetic epilepsy, adding oral felbamate resulted in an impressive 82% reduction in seizure frequency over a short-term period, with 83% of dogs showing a significant response.

Long-term follow-up (averaging 13 months) indicated that 67% of the dogs remained responders, achieving an average seizure reduction of 98%, and some dogs maintained seizure-free status, suggesting that felbamate could be a promising add-on treatment for resistant cases of canine epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Felbamate as an oral add-on therapy in six dogs with presumptive idiopathic epilepsy and generalized seizures resistant to drug therapy. Dewey, CW., Rishniw, M., Sakovitch, K.[2022]

Felbamate was the first antiepileptic drug to undergo innovative clinical trials, including double-blind studies in patients withdrawn from other AEDs and in children with Lennox-Gastaut syndrome, highlighting its unique development process.

Despite its initial success and marketing as a safe alternative to other AEDs, felbamate faced serious safety concerns due to cases of fatal bone marrow aplasia and liver toxicity, leading to a significant risk of market withdrawal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Felbamate. Bourgeois, BF.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06262594

Lemborexant Treatment of Insomnia Linked to Epilepsy It identifies the role of the intervention that participants receive. Types of arms include experimental arm, active comparator arm, placebo comparator arm, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7487867/

results from the phase 3 randomized clinical trial SUNRISE 2 LEM5 and LEM10 provided significant benefit on sleep onset and sleep maintenance in individuals with insomnia disorder versus placebo, and was well tolerated.

3. media-us.eisai.com media-us.eisai.com/2021-04-16-Eisai-Presents-Breadth-of-Data-Across-Neurology-Portfolio-Including-Alzheimers-Disease-Insomnia-and-Epilepsy

Eisai Presents Breadth of Data Across Neurology Portfolio ... Five posters with DAYVIGO data will be presented, including analyses of its effect on a range of sleep measures and patient-reported outcomes.

4. sciencedirect.com sciencedirect.com/science/article/pii/S1389945721000654

Long-term effectiveness and safety of lemborexant in ... Lemborexant is a recently approved treatment for adults with insomnia. Over 12 months, lemborexant was effective for all sleep parameters assessed.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5656478/

Lemborexant, A Dual Orexin Receptor Antagonist (DORA) ... Conclusions: Lemborexant doses ranging from 2.5–10 mg provided efficacy for the treatment of insomnia while minimizing next-morning residual sleepiness.

6. dhpp.hpfb-dgpsa.ca dhpp.hpfb-dgpsa.ca/review-documents/resource/SBD00529

Summary Basis of Decision for Dayvigo Clinical Safety. The clinical safety of Dayvigo was based on data from 20 clinical studies involving 3,371 participants. Of these studies, 16 were Phase I ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2019/212028Orig1s000MultidisciplineR.pdf

Multi-Discipline Review - accessdata.fda.gov ... lemborexant would provide greater benefit than the currently marketed orexin receptor antagonist. The safety database for lemborexant ...