Cenobamate for Epilepsy

Recruiting at 44 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: SK Life Science, Inc.

Must not be taking: Illicit drugs

Disqualifiers: Significant medical history changes, 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: 2

145 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

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}

What makes the drug Cenobamate unique for treating epilepsy?

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

What is the purpose of this trial?

This trial aims to ensure the safety of cenobamate, a seizure control medication, for patients who have already participated in a previous study. Cenobamate helps by calming overactive brain signals that cause seizures. Cenobamate is a new medication approved by the FDA in 2019 for the treatment of focal-onset seizures in adults.

Research Team

Sunita Misra, MD

Principal Investigator

SK Life Science, Inc.

Eligibility Criteria

This trial is for individuals who have completed the core study YKP3089C025 and are dealing with epilepsy or seizures. They must provide written consent, and if unable to do so themselves, a legal guardian's consent along with their assent is required. Participants should not have used illicit drugs (except for THC/Cannabinoids) recently or had significant medical changes that could impact safety.

Inclusion Criteria

The subject must have successfully completed the Double-blind Treatment Period in the Core study

Written informed consent signed by the subject or legal guardian, in accordance with the International Council for Harmonisation (ICH) Good Clinical Practice (GCP) guidelines. If the written informed consent is provided by the legal guardian because the subject is unable to do so, a written or verbal assent from the subject must also be obtained. As required by country-specific regulations, only the subject may sign the ICF in accordance with ICH guidelines.

Exclusion Criteria

I tested positive for drugs, but not for THC or cannabinoids.

Any significant changes to the subject's medical history that, in the opinion of the Principal Investigator, could affect the subject's safety or conduct of the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Conversion

Subjects who received placebo in the double-blind study will be converted to cenobamate over 12 weeks, with dose titration every two weeks.

12 weeks

Regular visits every 2 weeks

Open-label Treatment

Subjects will receive open-label, flexibly dosed cenobamate for 40 weeks.

40 weeks

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cenobamate

Trial Overview The trial involves a 52-week open-label extension where participants will continue using Cenobamate, an anti-seizure medication previously studied in the core study. The focus is on assessing the long-term safety of this drug in those who've already received it.

Participant Groups

Group I: Core Study Placebo Experimental Treatment 1 Intervention

Subjects who did not receive Cenobamate in the Core Study will receive Cenobamate 12.5 mg tablet once a day for two weeks, 25 mg tablet once a day for two weeks, 50 mg tablet once a day for two weeks, 100 mg tablets once a day for two weeks, 150 mg tablets once a day for two weeks and 200 mg tablets once a day for twelve weeks. Adolescents will follow the same every two week regimen and receive cenobamate as an oral suspension based on weight.

Group II: Core Study Active Experimental Treatment 1 Intervention

Subjects who received cenobamate in the Core study will continue to receive the same daily dose (150 mg or 200mg). Adolescents will follow the same every two week regimen and receive cenobamate as an oral suspension based on weight.

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]