Cenobamate for Seizures

Recruiting in Palo Alto (17 mi)

+118 other locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: SK Life Science, Inc.

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests cenobamate, a new medication for controlling seizures, in adults and adolescents with a specific type of epilepsy. The medication is taken regularly to stabilize brain activity and reduce seizures. Cenobamate has shown high effectiveness in previous studies.

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.

What data supports the idea that Cenobamate for Seizures is an effective drug?

The available research shows that Cenobamate is effective in treating seizures. In a study, patients with difficult-to-treat focal epilepsy experienced a reduction in seizure frequency when using Cenobamate. Another study highlighted that Cenobamate was approved in the USA after successful trials showed it helped reduce partial-onset seizures in adults. Additionally, a long-term study found that patients continued to have fewer seizures over time with Cenobamate. These findings suggest that Cenobamate is a promising option for people who have not responded well to other treatments. ^{1 2 3 4 5}

What safety data is available for cenobamate in treating seizures?

Safety data for cenobamate, also known as Xcopri, Ontozry, and YKP3089, has been evaluated in several studies. These include a long-term open-label extension study assessing safety and tolerability, a multicentre double-blind randomized placebo-controlled trial focusing on safety and efficacy, and a study on sudden unexpected death in epilepsy (SUDEP) during its clinical development. Additionally, cenobamate has been approved in the USA for treating partial-onset seizures in adults based on pivotal phase 2 trials. ^{2 3 4 6 7}

Is the drug Cenobamate a promising treatment for seizures?

Yes, Cenobamate is a promising drug for treating seizures. It has been approved in the USA for adults with partial-onset seizures and has shown effectiveness in patients who have not responded well to other treatments. It works by targeting specific brain activities to help control seizures, making it a valuable option for those with difficult-to-treat epilepsy. ^{2 3 8 9 10}

Research Team

Sunita Misra, MD

Principal Investigator

SK Life Science, Inc.

Eligibility Criteria

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

I am not pregnant, lactating, or breastfeeding.

I was hospitalized for a severe seizure within the last year.

Subject has participated in previous cenobamate clinical studies.

Treatment Details

Interventions

• Cenobamate (Anti-epileptic drug)
• Placebo (Other)

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.

Participant Groups

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+

Findings from Research

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]

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 (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 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]

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]

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 (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 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

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

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

Cenobamate: First Approval. [2020]

3. 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]

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. Denmark pubmed.ncbi.nlm.nih.gov

Efficacy and safety of cenobamate in patients with uncontrolled focal seizures: A meta-analysis. [2021]

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

Long-term individual retention with cenobamate in adults with focal seizures: Pooled data from the clinical development program. [2022]

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

Sudden unexpected death in epilepsy during cenobamate clinical development. [2023]

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

Cenobamate in Generalized Epilepsy and Combined Generalized and Focal Epilepsy. [2023]

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

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

10. England pubmed.ncbi.nlm.nih.gov

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