Cenobamate for Seizures

No longer recruiting at 140 trial locations

Overseen By Denise Bonhomme

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: SK Life Science, Inc.

Must be taking: Anti-epileptic drugs

Must not be taking: Diazepam, Phenytoin, Antidepressants, others

Disqualifiers: Pregnancy, Lennox-Gastaut, Drug abuse, others

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

Compensation: Varies

Number of Visits: 3

Duration: 22 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medication, cenobamate, to evaluate its safety and effectiveness in treating Primary Generalized Tonic-Clonic (PGTC) seizures, which cause muscle stiffness and jerking. Participants will take either cenobamate or a placebo (a sugar pill) while continuing their usual seizure medications. Suitable candidates should have experience with PGTC seizures and have experienced at least five of these seizures in the last 12 weeks. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment.

Do I have to stop taking my current medications for the trial?

No, you can continue taking your current anti-epileptic drugs (AEDs) during the trial. The protocol allows you to stay on 1 to 3 AEDs with fixed dosing regimens. However, certain medications like diazepam (except as a rescue medication) and others listed in the exclusion criteria cannot be taken. If you're on benzodiazepines, the dosage must remain unchanged throughout the study.

Will I have to stop taking my current medications?

No, you will not have to stop taking your current anti-epileptic drugs (AEDs). The trial allows you to continue your usual AEDs while participating.

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

Research has shown that cenobamate is generally safe for patients. In one study, more than 60% of patients experienced a significant reduction in seizure frequency with cenobamate. This indicates the drug is effective and usually safe. Another study found that patients taking cenobamate had up to twice the reduction in seizures compared to those on a placebo. These results strongly suggest that cenobamate can be safely used, although it may have some side effects. Prospective trial participants should know that cenobamate has been tested in other studies and found to be effective and generally well-tolerated. ^{1 2 3 4 5}

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

Cenobamate is unique because it works differently from most existing seizure medications. While many current options focus on altering neurotransmitter levels, cenobamate targets and modulates sodium channels and enhances GABA-A receptor currents, which could lead to better control of seizures. Researchers are excited about cenobamate because it has shown the potential for faster and more effective seizure reduction with a once-daily dosing regimen. This could mean more convenient and consistent seizure management for patients compared to some current treatments that require multiple doses throughout the day.

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

Research has shown that cenobamate, which participants in this trial may receive, is a promising treatment for seizures. Studies indicate that this medication has reduced seizures in about 62% of people, with some experiencing their seizures cut in half. Notably, about 21% of patients taking the highest dose became completely seizure-free. These results suggest cenobamate can be very effective, especially for those who haven't had success with other treatments. ^{1 2 6 7 8}

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 males and females aged 12 or older with Primary Generalized Tonic-Clonic (PGTC) seizures, who are on a stable dose of up to three anti-epileptic drugs. They must not be pregnant, breastfeeding, have certain medical conditions or history of drug abuse. Participants need to use birth control if applicable and have had recent brain imaging tests.

Inclusion Criteria

You've had a CT scan or MRI within the past 10 years that showed you don't have a worsening condition causing epilepsy.

Written informed consent signed by the subject or legal guardian, or legally authorized representative (LAR), in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) guidelines.

You can follow a ketogenic diet if your condition is stable.

Exclusion Criteria

Subject has participated in previous cenobamate clinical studies.

You have a history of occasionally using benzodiazepines for emergency situations.

Subject has received an investigational drug or device within 30 days prior to Visit 1 (Screening/Baseline).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-randomization

Baseline seizure frequency is established

4 weeks

Treatment

Participants receive cenobamate or placebo with a 10-week titration phase followed by a 12-week maintenance phase

22 weeks

Regular visits every 2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a one-week down titration

3 weeks

1 follow-up visit

Open-label extension (optional)

Eligible participants may opt into a continuation of treatment in an open-label safety study

What Are the Treatments Tested in This Trial?

Interventions

• Cenobamate
• Placebo

Trial Overview

The study tests the safety and effectiveness of Cenobamate as an additional treatment for epilepsy against a placebo. Participants will take either Cenobamate or a sugar pill alongside their current medications over a period of 22 weeks, followed by a 3-week follow-up.

How Is the Trial Designed?

Group I: Cenobamate Experimental Treatment 1 Intervention

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: Placebo Placebo Group 1 Intervention

Matching placebo

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]

Cenobamate significantly reduced seizure frequency in patients with uncontrolled focal seizures, with a 50% reduction achieved by more than double the number of patients compared to placebo (RR 2.06), particularly at the effective dose of 400 mg (RR 2.28).

The treatment was generally well tolerated, with most adverse events being mild to moderate, although a higher dropout rate was observed at the 400 mg dose compared to placebo (RR 2.09).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of cenobamate in patients with uncontrolled focal seizures: A meta-analysis. Zhang, L., Wang, J., Wang, C.[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 (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]

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, 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 involving 2132 patients treated with cenobamate for a total of 5693 person-years, the all-cause mortality rate was found to be 4.0 per 1000 person-years, indicating a relatively low risk of death among those with uncontrolled focal epilepsy.

The study identified 5 cases of sudden unexpected death in epilepsy (SUDEP), all of which occurred in patients with focal to bilateral tonic-clonic seizures, suggesting that while cenobamate is effective, patients with this specific seizure type may still be at risk for SUDEP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sudden unexpected death in epilepsy during cenobamate clinical development. Rosenfeld, WE., Ferrari, L., Kerr, WT., et al.[2023]

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]

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]

In a study involving 1844 participants, cenobamate demonstrated high retention rates of 80% at 1 year and 72% at 2 years, indicating its long-term efficacy and tolerability as an adjunctive treatment for uncontrolled focal seizures.

The most common reasons for discontinuation were adverse events (37.6%) and withdrawal of consent (21.1%), suggesting that while cenobamate is generally well-tolerated, some patients may experience side effects that lead them to stop treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term individual retention with cenobamate in adults with focal seizures: Pooled data from the clinical development program. Sander, JW., Rosenfeld, WE., Halford, JJ., et al.[2022]

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