Cenobamate for Focal Seizures

Not currently recruiting at 38 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the effectiveness of cenobamate, an anti-seizure medication, as the sole treatment for adults with focal seizures, a type of epilepsy that begins in one part of the brain. It will evaluate the effectiveness of 100 mg/day and 200 mg/day doses for individuals who are newly diagnosed or have experienced a recurrence of seizures. The trial suits adults who have had at least two unprovoked seizures in the past year or one recent seizure with a high risk of recurrence. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and proven effective treatment benefits a broader patient population.

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 is the safety track record for Cenobamate?

Research has shown that cenobamate is generally well-tolerated by people with focal seizures. One study found that cenobamate effectively controls seizures and is well-tolerated by patients. Another report examined its long-term use and found it safe for people with uncontrolled focal seizures, indicating they did not experience many severe side effects over time.

Cenobamate's approval for focal seizures in adults in the U.S. and other countries supports its safety, as it has met strict safety standards for treating these seizures. Overall, current data suggest that cenobamate is a safe option for managing focal seizures. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for focal seizures, which often include medications like carbamazepine or lamotrigine, cenobamate is unique because it has a dual mechanism of action. It not only enhances the function of GABA (an inhibitory neurotransmitter that calms down nerve activity) but also reduces the persistent sodium currents that can cause seizures. This dual action allows cenobamate to potentially offer more effective seizure control. Researchers are particularly excited about cenobamate because it has shown promise in reducing seizure frequency more significantly than many existing options, potentially offering new hope to those who haven't found relief with the current standard therapies.

What is the effectiveness track record for Cenobamate as a treatment for focal seizures?

Research shows that cenobamate helps reduce seizures. Studies found that people taking cenobamate experienced up to twice the seizure reduction compared to those on a placebo. For some, seizures decreased from about 21 per month to just four. Long-term use of cenobamate has proven safe and effective, significantly improving seizure control for many adults. This medication is already approved for treating focal seizures, with its effectiveness well-supported by existing evidence. All enrolled subjects in this trial will participate in the Cenobamate arm, as this is a single-arm study. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

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

Subject and/or caregiver(s)/legal representative must be willing and able to give informed assent/consent for participation in the study

Subject and their caregiver must be willing and able to comply with all study requirements

Exclusion Criteria

I am currently pregnant, breastfeeding, or planning to become pregnant.

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

Subjects with history of drug or alcohol dependency or abuse within the last 2 years before the Pretreatment Period

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 (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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31734103/

Safety and efficacy of adjunctive cenobamate (YKP3089) in ... The primary efficacy outcomes were percentage change in 28-day focal seizure frequency (focal aware motor, focal impaired awareness, or focal to bilateral ...

2. xcoprihcp.com xcoprihcp.com/efficacy/

XCOPRI® (cenobamate tablets) CV Efficacy Primary outcome: Patients taking XCOPRI experienced up to 2x greater seizure reduction compared with placebo (55% XCOPRI 400 mg, 55% XCOPRI 200 mg, ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2589986422000107

Effectiveness and safety of adjunctive cenobamate for focal ... Adjunctive cenobamate treatment through 6 months led to reduced mean focal seizure frequency from 20.9 seizures (median = 3.0) per month to 4.1 seizures (median ...

4. practicalneurology.com practicalneurology.com/news/long-term-real-world-study-results-show-xcopri-is-highly-effective-as-a-treatment-for-reducing-seizures/2470359/

Long-Term, Real-World Study Results Show Xcopri Is Highly ... Long-term treatment with Xcopri (cenobamate tablet; SK Life Sciences, Paramus, NJ) was safe and highly effective in reducing seizure frequency.

5. neurology.org neurology.org/doi/10.1212/WNL.0000000000009530

Randomized phase 2 study of adjunctive cenobamate in ... Adjunctive treatment with cenobamate 200 mg/d significantly improved seizure control in adults with uncontrolled focal seizures and was well tolerated.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01397968

NCT01397968 | Efficacy and Safety of YKP3089 in ... Long-term safety of adjunctive cenobamate in patients with uncontrolled focal seizures: Open-label extension of a randomized clinical study. Epilepsia. 2021 ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1059131125001104

Efficacy and safety of Cenobamate: a multicenter ... Cenobamate is a highly effective and well-tolerated ASM for patients with DRE, offering significant clinical benefits, including improved seizure control and ...

8. neurology.org neurology.org/doi/10.1212/WNL.94.15_supplement.1030

Safety of Cenobamate for the Treatment of Focal Seizures ... Objective: To assess safety of cenobamate in patients with uncontrolled focal seizures when titrated weekly (1W) or every other week (2W).