Cenobamate (Xcopri) for Seizures

Recruiting at12 trial locations

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

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

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called cenobamate to see how it works in children who have a specific type of seizure. The study will look at how the drug moves through the body and how safe it is when taken over time. Cenobamate aims to calm overactive brain signals that cause these seizures.

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.

What data supports the effectiveness of the drug Cenobamate (Xcopri) for treating seizures?

Cenobamate has been shown to be effective in treating partial-onset seizures in adults, as demonstrated by two pivotal phase 2 trials and its subsequent approval by the FDA. Additionally, real-world experiences and studies have confirmed its robust efficacy in patients whose seizures were not controlled by other treatments. ^{1 2 3 4 5}

Is cenobamate generally safe for humans?

Cenobamate has been tested in various studies and is generally well-tolerated in humans, with most side effects being mild. Serious side effects were rare, and no deaths were reported in the studies. ^{1 2 3 5 6}

What makes the drug cenobamate unique for treating seizures?

Cenobamate is unique because it has a dual mechanism of action, blocking persistent sodium currents and enhancing the activity of the GABA-A receptor, which helps calm the brain. It is specifically approved for adults with focal-onset seizures who haven't responded to at least two other seizure medications. ^{1 2 4 7 8}

Research Team

Marc Kamin, MD

Principal Investigator

SK Life Science, Inc.

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Cenobamate (YKP3089) (Anti-epileptic drug)

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

SK Life Science, Inc.

Lead Sponsor

Trials

42

Recruited

8,900+

Findings from Research

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]

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]

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]

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, 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, 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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Cenobamate: First Approval. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Initial Real-World Experience With Cenobamate in Adolescents and Adults: A Single Center Experience. [2022]

3. England 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. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Use of cenobamate for the treatment of focal epilepsy: an Italian expert opinion paper. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Cenobamate: Results From Single and Multiple Oral Ascending-Dose Studies in Healthy Subjects. [2021]

6. United States 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. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Cenobamate in Generalized Epilepsy and Combined Generalized and Focal Epilepsy. [2023]

8. New Zealand pubmed.ncbi.nlm.nih.gov

An Ex Vivo Evaluation of Cenobamate Administered via Enteral Tubes. [2020]