Cenobamate for Epilepsy

Enrolling by invitation at 58 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of a medication called cenobamate for people with epilepsy. It is an open-label study, meaning everyone will know they are receiving the medication, to assess its safety over a year. Participants who have completed a previous related study are eligible to join. Those who have finished the core study and wish to continue treatment may find this trial suitable. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the chance to contribute to the potential availability of a new epilepsy treatment.

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.

Is there any evidence suggesting that cenobamate is likely to be safe for humans?

Research has shown that cenobamate is generally well-tolerated. In studies, some participants stopped taking the medication due to side effects, with rates of 11% for those taking 100 mg, 9% for 200 mg, and 21% for 400 mg, compared to 4% for those on a placebo. This indicates that a small percentage experienced issues leading to discontinuation.

The FDA has approved cenobamate for treating certain types of seizures in adults, indicating its safety for use in some cases. However, like any medication, some individuals may experience side effects. Most participants reported a significant reduction in seizure frequency, which is a positive outcome.

Overall, the treatment appears safe for many, but individual experiences may vary. It is important to discuss any concerns with a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for epilepsy?

Researchers are excited about cenobamate for epilepsy because it offers a unique way to control seizures that sets it apart from standard treatments like levetiracetam or lamotrigine. Unlike most current options that primarily focus on one type of neurotransmitter, cenobamate works by enhancing inhibitory neurotransmission while also reducing excitatory neurotransmission. This dual-action mechanism could potentially offer better seizure control. Additionally, cenobamate has shown promise in reducing seizure frequency more quickly, which is a significant advantage for individuals seeking faster relief.

What evidence suggests that cenobamate might be an effective treatment for epilepsy?

Research has shown that cenobamate can effectively reduce seizures in people with epilepsy. In one study, about 62% of patients experienced at least a 50% reduction in seizures. Another study found that 21% of patients became completely seizure-free. These findings suggest that cenobamate can be a strong option for managing epilepsy. In this trial, participants in the Core Study Active arm will continue receiving cenobamate at their current dose, while those in the Core Study Placebo arm will gradually increase their cenobamate dosage. Long-term studies have also confirmed its effectiveness and safety in reducing seizures. ^{6 7 8 9 10}

Who Is on the Research Team?

Sunita Misra, MD

Principal Investigator

SK Life Science, Inc.

Are You a Good Fit for This Trial?

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

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.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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, 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]

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 (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 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, 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) 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40119878/

Real-world effectiveness and tolerability of cenobamate in ... The primary effectiveness endpoint was the 50% responder rate, defined as the reduction in seizure frequency ≥50%. Results: Data were collected ...

2. seizure-journal.com seizure-journal.com/article/S1059-1311(25)00110-4/fulltext

Efficacy and safety of Cenobamate: a multicenter ... 288 patients (61.9 %) responded to treatment, achieving ≥50 % reduction in seizure frequency, including 77 patients (16.5 %) not experiencing ...

3. xcoprihcp.com xcoprihcp.com/efficacy/

XCOPRI® (cenobamate tablets) CV Efficacy The primary outcome was median percentage reduction in 28-day seizure frequency during the double-blind treatment period. In Study 1, patients were started on a ...

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11263269/

Evidence from the First Interim Analysis of the BLESS Study Cenobamate demonstrated its efficacy in two randomized placebo-controlled trials (RCTs), and it was associated with a seizure-free rate of 21.0% ...

6. xcoprihcp.com xcoprihcp.com/safety/

XCOPRI® (cenobamate tablets) CV Safety Discontinuation rates due to adverse reactions were 11% (100 mg), 9% (200 mg), and 21% (400 mg) for patients on XCOPRI compared with 4% for patients on ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10456719/

Cenobamate (YKP3089) and Drug-Resistant Epilepsy CNB is a highly effective drug in managing focal onset seizures, with more than twenty percent of individuals with drug-resistant epilepsy achieving seizure ...

8. sklifescienceinc.com sklifescienceinc.com/pdf/Long_Term_Efficacy_and_Safety_Data_of_XCOPRI%C2%AE_cenobamate_tablets_CV_Published_in_Neurology.pdf

Long-Term Efficacy and Safety Data of XCOPRI® ( ... “More than three quarters of patients treated with cenobamate experienced a reduction in seizure frequency of. 50% or more during years 3-4 of ...

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/212839s006s007lbl.pdf

Prescribing Information - accessdata.fda.gov A total of 658 patients (442 patients treated with XCOPRI and 216 patients treated with placebo) constituted the safety population in the pooled analysis of ...

10. xcopri.com xcopri.com/

Epilepsy Medication | XCOPRI (cenobamate tablets) CV XCOPRI® (cenobamate tablets) CV is a prescription medicine used to treat partial-onset seizures in adults. IMPORTANT SAFETY INFORMATION. DO NOT TAKE XCOPRI IF ...