Cenobamate for Focal Seizures

Recruiting at 41 trial locations

Overseen By Shelby Parilla

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: SK Life Science, Inc.

Must not be taking: Strong CYP3A inducers

Disqualifiers: Lennox-Gastaut, Status epilepticus, Psychogenic seizures, others

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

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: 15

90 Participants Needed

Trial Summary

What is the purpose of this trial?

Cenobamate (YKP3089) is a small molecule approved in the United States (US), Europe and several other countries around the world for the treatment of Partial-Onset (focal) seizures in adult subjects (≥18 years of age). In the US it is approved for use as monotherapy, however, there is little clinical data assessing its use as monotherapy in adults with POS. This study is designed to explore the effectiveness of doses of 100 mg/day and 200 mg/day as monotherapy in adult subjects with newly diagnosed or recurrent POS/focal onset epilepsy.

Will I have to stop taking my current medications?

If you are currently taking a low dose of one anti-seizure medication (ASM) and have been for 12 weeks or less, you may need to stop or reduce it within 6 weeks after starting cenobamate, depending on the doctor's decision. The protocol does not specify for other medications, so it's best to discuss with the study team.

What data supports the effectiveness of the drug Cenobamate for treating focal seizures?

Cenobamate has shown effectiveness in treating focal seizures, as evidenced by its approval in the USA following successful phase 2 trials. It has demonstrated broad-spectrum anticonvulsant activity and has been used in real-world settings to help patients whose seizures were not controlled by other treatments. ^{1 2 3 4 5}

Is cenobamate safe for humans?

Cenobamate has been studied for safety in treating focal seizures, and it has been approved by the FDA for use in adults. Some patients have experienced side effects like drug-related rashes, but it is generally considered safe when used as directed. ^{1 2 3 4 6}

How is the drug cenobamate different from other treatments for focal seizures?

Cenobamate is unique because it is a new antiseizure medication that has shown broad-spectrum anticonvulsant activity and is effective for patients whose seizures are not controlled by other treatments. It is taken once daily and has a long half-life, meaning it stays in the body longer, which can help maintain steady levels of the drug. ^{1 3 4 7 8}

Eligibility Criteria

Adults aged 18-74 with newly diagnosed or recurrent partial-onset seizures are eligible for this trial. They must have had at least two unprovoked seizures in the past year, be able to track their seizures and side effects, and women of childbearing age must use birth control. Those on low-dose seizure medication may qualify if it can be safely stopped.

Inclusion Criteria

Subjects must be considered reliable and willing to be available for the study period and able to record seizures and report adverse events (AEs) themselves or have a caregiver who can do so for them

I have epilepsy with at least 2 seizures in the last year, not caused by a known trigger.

I am not able to have children or I am following an approved birth control method.

Exclusion Criteria

I experience seizures that happen so close together they can't be counted individually.

I haven't taken strong CYP3A inducers in the last 12 weeks.

I've used emergency medication at least twice in the last month.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

3 weeks

1 visit (in-person)

100 mg/day Treatment

Participants receive cenobamate starting with a 6-week Titration Phase followed by a 26-week Maintenance Phase at 100 mg/day

32 weeks

Regular visits as per protocol

200 mg/day Treatment

Participants transition to 200 mg/day cenobamate with a 2-week Titration Phase followed by a 26-week Maintenance Phase

28 weeks

Regular visits as per protocol

Optional Extension

Participants may opt into a 26-week Extension Period to continue treatment

26 weeks

Visits at 13th and 26th week

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Cenobamate

Trial Overview The study is testing Cenobamate as a single therapy at doses of 100 mg/day and 200 mg/day in adults with focal onset epilepsy. It aims to gather data on its effectiveness when used alone rather than combined with other medications.

Participant Groups

Group I: Cenobamate Experimental Treatment 1 Intervention

All enrolled subjects will automatically participate in the Cenobamate arm since this is a single-arm study.

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, 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 (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 demonstrated significant reductions in seizure frequency across all focal seizure subtypes over a 27-month period, with the most substantial reductions observed in focal to bilateral tonic-clonic seizures, achieving up to 100% seizure reduction in some patients.

The treatment was generally well-tolerated, with common side effects including fatigue, dizziness, and somnolence, but no cases of serious skin reactions (DRESS) were reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of cenobamate by focal seizure subtypes: Post-hoc analysis of a phase 3, multicenter, open-label study. Rosenfeld, WE., Ferrari, L., Kamin, M.[2022]

Cenobamate significantly reduced seizure frequency in patients with uncontrolled focal epilepsy, achieving a median percentage change of 56% compared to 22% for placebo in a phase 2 trial, indicating strong efficacy as an adjunctive treatment.

The safety profile of cenobamate is comparable to other antiseizure medications, with neurological side effects being the most common; however, there is a notable concern regarding the risk of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cenobamate: A New Adjunctive Agent for Drug-Resistant Focal Onset Epilepsy. Buckley, CT., Waters, OR., DeMaagd, G.[2021]

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 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]

References

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

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

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

Cenobamate: First Approval. [2020]

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

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

5. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy of cenobamate by focal seizure subtypes: Post-hoc analysis of a phase 3, multicenter, open-label study. [2022]

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

Cenobamate: A New Adjunctive Agent for Drug-Resistant Focal Onset Epilepsy. [2021]

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

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

8. England pubmed.ncbi.nlm.nih.gov

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