Cenobamate for Epilepsy

Recruiting at 44 trial locations

Overseen By Temitayo Oyegbile-Chidi, MD

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: SK Life Science, Inc.

Must be taking: Antiepileptic drugs

Must not be taking: Vigabatrin, Rescue benzodiazepines

Disqualifiers: Pregnancy, Pseudo-seizures, Psychiatric disorders, others

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

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: 3 years

140 Participants Needed

Trial Summary

What is the purpose of this trial?

Primary objective: To evaluate the safety and tolerability of cenobamate in pediatric subjects 2-17 years of age with partial-onset (focal) seizures

Will I have to stop taking my current medications?

The trial does not require you to stop your current medications. Participants must be on stable doses of 1 to 3 approved antiepileptic drugs for at least 4 weeks before starting the trial.

What data supports the effectiveness of the drug Cenobamate for epilepsy?

Cenobamate has been shown to be effective in reducing seizures in adults with partial-onset epilepsy, as demonstrated in multiple studies, including pivotal phase 2 trials and a long-term open-label extension study. It has been approved in the USA for this use, indicating its effectiveness in managing seizures. ^{1 2 3 4 5}

Is cenobamate safe for humans?

Cenobamate has been studied in both healthy individuals and patients with epilepsy, showing that most side effects were mild, with only two serious cases reported and no deaths. It was generally well tolerated at doses up to 500 mg per day, although higher doses (600 mg) were less tolerated. ^{1 2 3 5 6}

How is the drug Cenobamate different from other epilepsy treatments?

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 also designed for once-daily dosing, making it convenient for patients. ^{1 2 5 7 8}

Research Team

Marc Kamin, MD

Principal Investigator

SK Life Science, Inc.

Eligibility Criteria

This trial is for children aged 2-17 with partial-onset seizures and a stable epilepsy diagnosis. They must weigh at least 10 kg, have had an MRI or CT scan within the last 10 years, be on a steady dose of up to three antiepileptic drugs (excluding VNS), and may also be on a ketogenic diet. Pregnant or breastfeeding females, those with certain psychiatric conditions, significant diseases, recent investigational drug use, specific genetic intolerances or severe renal/hepatic insufficiency are excluded.

Inclusion Criteria

I have never had liver or blood problems from taking felbamate.

I have been diagnosed with epilepsy that starts in one area of my brain for over a year.

I have been taking felbamate for at least a year and have been on a stable dose for the last 60 days.

Exclusion Criteria

I've used emergency anxiety medication more than once in the last month.

Have an unstable psychiatric diagnosis that may confound participants' ability to participate in the study or that may prevent completion of the protocol-specified tests (e.g., significant suicide risk, including suicidal behavior and ideation within 6 months before Visit 1 (Screening), current psychotic disorder, acute mania).

I have been diagnosed with Familial Short QT Syndrome.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cenobamate tablets and suspension to evaluate safety, tolerability, and efficacy

3 years

Regular visits for safety and efficacy assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cenobamate

Trial Overview The study tests the safety and effectiveness of Cenobamate (Xcopri) in young patients with focal seizures. It aims to see how well they tolerate this medication and if it helps control their seizures better than their current treatment regimen.

Participant Groups

Group I: 6 to <12 years old Experimental Treatment 1 Intervention

Group II: 4 to <6 years old Experimental Treatment 1 Intervention

Group III: 2 to <4 years old Experimental Treatment 1 Intervention

Group IV: 12 to < 18 year olds Experimental Treatment 1 Intervention

Cenobamate is already approved in United States, European Union, United Kingdom, Canada for the following indications:

Approved in United States as Xcopri for:

• Partial-onset seizures in adults

Approved in European Union as Ontozry for:

• Adjunctive treatment of focal-onset seizures with or without secondary generalization in adults with epilepsy who have not been adequately controlled despite a history of treatment with at least two anti-epileptic medications

Approved in United Kingdom as Ontozry for:

• Add-on treatment for focal-onset seizures with or without secondary generalization in adults with epilepsy who have not been adequately controlled despite a history of treatment with at least one other add-on treatment

Approved in Canada as Ontozry for:

• Adjunctive treatment of focal-onset seizures with or without secondary generalization in adults with epilepsy who have not been adequately controlled despite a history of treatment with at least two anti-epileptic medications

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]

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 study of 51 patients with highly refractory focal epilepsy, cenobamate demonstrated an 80.4% retention rate at the last follow-up, indicating its effectiveness in long-term treatment.

The treatment resulted in a 56.5% responder rate for focal seizures and a 63.6% responder rate for focal to bilateral tonic-clonic seizures at three months, with a manageable safety profile as 43.1% of patients reported treatment-emergent adverse events, most of which resolved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cenobamate in patients with highly refractory focal epilepsy: A retrospective real-world study. Beltrán-Corbellini, Á., Romeral-Jiménez, M., Mayo, P., et al.[2023]

Cenobamate (CNB) demonstrated long-term efficacy in reducing seizure frequency, with a median reduction of 76.1% at 43-48 months, and 16.4% of patients achieving complete seizure freedom during this period.

The treatment was well-tolerated over the long term, with retention rates of 71% at 24 months and no new safety issues identified, although common adverse events included dizziness and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Efficacy and Safety From an Open-Label Extension of Adjunctive Cenobamate in Patients With Uncontrolled Focal Seizures. Klein, P., Aboumatar, S., Brandt, C., et al.[2022]

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]

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, 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 (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]

References

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

Cenobamate: First Approval. [2020]

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

Cenobamate in patients with highly refractory focal epilepsy: A retrospective real-world study. [2023]

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

Long-Term Efficacy and Safety From an Open-Label Extension of Adjunctive Cenobamate in Patients With Uncontrolled Focal Seizures. [2022]

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

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

7. 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]

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

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