Cenobamate (Xcopri) for Seizures

Recruiting at 15 trial locations

Overseen By Sunita Misra, MD, PhD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: SK Life Science, Inc.

Must be taking: Antiepileptic drugs

Must not be taking: Phenytoin, Clobazam, Vigabatrin

Disqualifiers: Progressive neurological disease, Hepatic failure, Renal failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 18 months

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to study how young patients with partial-onset seizures (a type of epilepsy that starts in one area of the brain) process a medication called cenobamate (also known as Xcopri). The trial will explore the effects of administering this medication in single and repeated doses. Children diagnosed with partial-onset seizures for at least six months and already on stable doses of one or two antiepileptic drugs may be suitable candidates for this study. As a Phase 1 trial, this research focuses on understanding how cenobamate works in people, offering participants the opportunity to be among the first to receive this treatment.

Will I have to stop taking my current medications?

You can continue taking your current antiepileptic drugs (AEDs) as long as the doses are stable for at least 4 weeks before the study starts. However, you must stop taking phenytoin, clobazam, and vigabatrin at least 30 days before the study begins.

Is there any evidence suggesting that cenobamate (Xcopri) is likely to be safe for humans?

Research has shown that cenobamate, also known as Xcopri, is generally well-tolerated by people with partial-onset seizures. In earlier studies, a small number of patients discontinued Xcopri due to side effects. Specifically, 11% of those taking 100 mg, 9% taking 200 mg, and 21% taking 400 mg stopped because of side effects, compared to only 4% of those not taking Xcopri.

While Xcopri is effective for many, it carries some risks. These include a serious allergic reaction called DRESS (drug reaction with eosinophilia and systemic symptoms) and changes in heart rhythm (QT shortening). Although rare, these risks underscore the need for careful monitoring during treatment.

Xcopri is already approved for adults, indicating its safety for this group is well-established. However, the current trial examines its effects in younger patients, showing that research continues for this age group. ^{1 2 3 4 5}

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

Cenobamate (Xcopri) is unique because it offers a new approach to treating seizures in children aged 2 to less than 18 years. Unlike standard treatments like valproic acid or lamotrigine, which primarily stabilize electrical activity in the brain, cenobamate enhances inhibitory neurotransmission by modulating sodium channels and boosting GABA (a calming brain chemical). Researchers are excited about cenobamate's potential to provide faster and more effective seizure control, potentially reducing seizure frequency and severity more quickly than current options. Additionally, its ability to be administered across a wide age range, from toddlers to teenagers, makes it a versatile option in pediatric epilepsy management.

What evidence suggests that cenobamate might be an effective treatment for seizures?

Research has shown that cenobamate, also known as Xcopri, can help reduce seizures. In studies, 61.9% of patients experienced at least a 50% reduction in seizures, and 37.3% stopped having seizures entirely. Another study found that nearly half of the participants experienced a significant drop in seizures after three months. These results suggest that cenobamate could be a promising option for managing seizures. Participants in this trial will receive cenobamate in different cohorts based on age, with dosages not exceeding 400 mg/day. ^{6 7 8 9 10}

Who Is on the Research Team?

Marc Kamin, MD

Principal Investigator

SK Life Science, Inc.

Are You a Good Fit for This Trial?

This trial is for children and teens aged 2 to less than 18 with epilepsy characterized by partial-onset seizures. They must have been diagnosed at least 6 months prior, weigh over 10 kg, be on a stable dose of up to two antiepileptic drugs (excluding vagal nerve stimulators), and not have significant health issues like heart problems or severe infections.

Inclusion Criteria

You can still join if you've been on a ketogenic diet for at least 30 days before the first visit and will continue this diet during the study.

In the Investigator's opinion, parents or caregivers must be able to report accurate seizure assessments during the screening and study periods and subjects must be able to ingest study drug

I am between 2 and 17 years old.

Exclusion Criteria

You have had a rash from taking certain seizure medications that also affected your eyes or mouth.

You had to stop taking a medication because you had a bad reaction to it more than once.

My white blood cell count is low, or I have very few infection-fighting cells.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive single and multiple doses of cenobamate (YKP3089) to assess pharmacokinetics and safety

18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cenobamate (YKP3089)

Trial Overview

The study tests the drug Cenobamate (YKP3089) in young patients with epilepsy to understand how the body processes it after one dose and multiple doses. It aims to find out how much of the drug gets into the bloodstream and how long it stays there.

How Is the Trial Designed?

Group I: Cohort IIb Experimental Treatment 1 Intervention

Xcopri to be administered to ages 4 to \< 6 years not to exceed 400 mg/day.

Group II: Cohort IIa Experimental Treatment 1 Intervention

Xcopri to be administered to ages 6 to \< 12 years not to exceed 400 mg/day.

Group III: Cohort III Experimental Treatment 1 Intervention

Xcopri to be administered to ages 2 to \< 4 years not to exceed 400 mg/day.

Group IV: Cohort I Experimental Treatment 1 Intervention

Xcopri to be administered to ages 12 to \< 18 years not to exceed 400 mg/day.

Cenobamate (YKP3089) is already approved in United States, European Union for the following indications:

Approved in United States as Xcopri for:

• Partial-onset seizures in adult patients

Approved in European Union as Xcopri for:

• Partial-onset seizures in adult patients

Who Is Running the Clinical Trial?

SK Life Science, Inc.

Lead Sponsor

Trials

42

Recruited

8,900+

Published Research Related to This Trial

Cenobamate is an effective new antiseizure medication for adults with focal-onset seizures, particularly for those who have not responded well to at least two other antiseizure medications, as authorized in the USA and Europe.

The Italian preliminary experience suggests that slow titration of cenobamate can enhance tolerability and that many patients may achieve significant benefits at lower doses, indicating its potential as a favorable treatment option for resistant epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of cenobamate for the treatment of focal epilepsy: an Italian expert opinion paper. Villani, F., Cianci, V., Di Bonaventura, C., et al.[2023]

Cenobamate, a new antiseizure medication, was found to be rapidly absorbed and well-tolerated in healthy Japanese subjects, with a maximum plasma concentration reached within 0.75 to 2.25 hours after a single oral dose.

The pharmacokinetics of cenobamate in Japanese individuals showed similar patterns to those observed in non-Japanese subjects, indicating comparable systemic exposure and safety across different populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and safety of cenobamate, a novel antiseizure medication, in healthy Japanese, and an ethnic comparison with healthy non-Japanese. Yang, E., Sunwoo, J., Huh, KY., et al.[2022]

Cenobamate, an FDA-approved oral antiepileptic drug for focal seizures, showed high recovery rates (96.3% to 101.7%) when administered through enteral feeding tubes, indicating effective delivery.

The study confirms that cenobamate does not adhere to or get absorbed by the feeding tubes, making it a suitable option for patients who have difficulty swallowing tablets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Ex Vivo Evaluation of Cenobamate Administered via Enteral Tubes. Ferrari, L., Nisman, A., Pegan, A., et al.[2020]

Cenobamate, an antiepileptic drug approved for focal seizures, demonstrated a favorable safety profile in a study involving 210 healthy subjects, with most treatment-emergent adverse events being mild and no deaths reported.

The pharmacokinetics of cenobamate support once-daily dosing, as it showed dose-proportional increases in plasma concentration and a long half-life of 30 to 76 hours, making it a convenient option for managing seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Cenobamate: Results From Single and Multiple Oral Ascending-Dose Studies in Healthy Subjects. Vernillet, L., Greene, SA., Kamin, M.[2021]

Cenobamate (CNB) shows promise as an effective antiseizure medication for patients with drug-resistant genetic generalized epilepsies (GGE) and combined generalized and focal epilepsies (CGFE), with a mean seizure reduction of 58% and a 70% responder rate in a retrospective review of 13 patients.

No patients experienced worsening of generalized-onset seizures while on CNB, although 77% reported side effects, indicating the need for careful management of treatment adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cenobamate in Generalized Epilepsy and Combined Generalized and Focal Epilepsy. Agashe, S., Worrell, G., Britton, J., et al.[2023]

Cenobamate (XCOPRI®) is a newly approved oral medication for treating partial-onset seizures in adults, developed by SK Life Science Inc. and Arvelle Therapeutics.

The approval was based on positive results from two pivotal phase 2 trials, highlighting its efficacy as a neurotherapeutic option for epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cenobamate: First Approval. Keam, SJ.[2020]

Cenobamate, an investigational drug, significantly reduced the frequency of focal seizures in patients with uncontrolled epilepsy, showing a dose-dependent effect with the highest reduction observed at 400 mg (55% decrease in seizure frequency).

While cenobamate was effective, treatment-emergent adverse events were more common at higher doses, with 90% of patients in the 400 mg group experiencing side effects, indicating a need for careful monitoring at increased dosages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of adjunctive cenobamate (YKP3089) in patients with uncontrolled focal seizures: a multicentre, double-blind, randomised, placebo-controlled, dose-response trial. Krauss, GL., Klein, P., Brandt, C., et al.[2020]

In a retrospective study of 45 patients, cenobamate was found to be effective for treating focal seizures, with a 60% response rate among participants, supporting its use beyond initial clinical trials.

Notably, patients with a history of drug-related rashes did not experience any rashes while on cenobamate, indicating it may be a safe option for this vulnerable group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial Real-World Experience With Cenobamate in Adolescents and Adults: A Single Center Experience. Elliott, T., Ridley-Pryor, T., Gienapp, AJ., et al.[2022]

Citations

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The median number of seizures/month was 8.8. After 3 months of maintenance, the 50% responder rate (primary endpoint) was 49.3%; the median ...

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Long-Term, Real-World Study Results Show Xcopri Is Highly ...

Long-Term, Real-World Study Results Show Xcopri Is Highly Effective as a Treatment for Reducing Seizures · 37.3% were 100% responders · 49.2% were ...

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The primary outcome was median percentage reduction in 28-day seizure frequency during the double-blind treatment period. In Study 1, patients were started on a ...

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pmc.ncbi.nlm.nih.gov/articles/PMC11263269/

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In adults with uncontrolled focal seizures, the treatment with adjunctive cenobamate was well tolerated and was associated with improved seizure control.

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xcoprihcp.com

xcoprihcp.com/safety/

XCOPRI® (cenobamate tablets) CV Safety

Discontinuation rates due to adverse reactions were 11% (100 mg), 9% (200 mg), and 21% (400 mg) for patients on XCOPRI compared with 4% for patients on ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10456719/

Cenobamate (YKP3089) and Drug-Resistant Epilepsy

CNB is a highly effective drug in managing focal onset seizures, with more than twenty percent of individuals with drug-resistant epilepsy achieving seizure ...

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Long-Term Efficacy and Safety Data of XCOPRI® ( ...

Results from the study showed the long-term clinical efficacy and safety of cenobamate for adult patients with partial-onset (focal) seizures.

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clinicaltrials.gov/study/NCT01397968

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This study is to evaluate the efficacy of YKP3089 in reducing seizure frequency when compared to baseline in subjects with partial onset seizures not fully ...

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accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/nda/2019/212839Orig1s000RiskR.pdf

Risk Assessment and Risk Mitigation Review(s)

The risks associated with cenobamate include drug reaction with eosinophilia and systemic symptoms (DRESS), QT shortening, and class risks ...