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}

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Brainstorm Research Miami, FL

Neuro Pain Medical Center Fresno, CA

Colorado Springs Neurological Associates Colorado Springs, CO

Children's Hospital of Colorado Grand Junction, CO

More Trial Locations

Who Is Running the Clinical Trial?

SK Life Science, Inc. Lead Sponsor

References

1. England pubmed.ncbi.nlm.nih.gov

Cenobamate in patients with highly refractory focal epilepsy: A retrospective real-world study. [2023] To determine the effectiveness and safety outcomes of cenobamate in a cohort of patients with highly refractory focal epilepsy in routine clinical practice.

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

Cenobamate: First Approval. [2020] Cenobamate (XCOPRI®) is an oral, small molecule neurotherapeutic azole compound that is being developed by SK Life Science Inc. and Arvelle Therapeutics for the treatment of epilepsy. Based on results of two pivotal phase 2 trials, cenobamate was recently approved in the USA for use in the treatment of partial-onset seizures in adult patients. This article summarizes the milestones in the development of cenobamate leading to this first approval.

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] More than a third of patients with epilepsy are treatment resistant, and thus new, more effective therapies to achieve seizure freedom are needed. Cenobamate (YKP3089), an investigational antiepileptic drug, has shown broad-spectrum anticonvulsant activity in preclinical studies and seizure models. We aimed to evaluate the safety, efficacy, and tolerability of adjunctive cenobamate in patients with uncontrolled focal (partial)-onset epilepsy.

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] Evaluate long-term efficacy (percent seizure frequency reduction and responder rates), safety, and tolerability of adjunctive cenobamate in an open-label extension (OLE) of the randomized, double-blind, placebo-controlled study.

5. Denmark pubmed.ncbi.nlm.nih.gov

Efficacy and safety of cenobamate in patients with uncontrolled focal seizures: A meta-analysis. [2021] To investigate the efficacy and safety of adjunctive cenobamate for treatment of uncontrolled focal seizures.

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] We determined retention on open-label cenobamate therapy in the clinical development program to assess the long-term efficacy and tolerability of adjunctive cenobamate in individuals with uncontrolled focal seizures.

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

Sudden unexpected death in epilepsy during cenobamate clinical development. [2023] We assessed mortality, sudden unexpected death in epilepsy (SUDEP), and standardized mortality ratio (SMR) among adults treated with cenobamate during the cenobamate clinical development program.

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

Cenobamate in Generalized Epilepsy and Combined Generalized and Focal Epilepsy. [2023] Cenobamate (CNB) is a United States Food and Drug Administration-approved antiseizure medication (ASM) for focal-onset seizures; however, its potential clinical effectiveness as a broad-spectrum ASM is not established. CNB has a proposed dual mechanism of action with preferential blockade of persistent sodium currents and positive allosteric modulation of the γ-aminobutyric acid-A (GABA-A) receptor. We evaluated the efficacy of CNB in drug refractory patients with genetic generalized epilepsies (GGE) or combined generalized and focal epilepsies (CGFE), including developmental and epileptic encephalopathies.

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

Pharmacokinetics of Cenobamate: Results From Single and Multiple Oral Ascending-Dose Studies in Healthy Subjects. [2021] Cenobamate (YKP3089) is an antiepileptic drug recently approved by the Food and Drug Administration for the treatment of focal (partial-onset) seizures in adults. The objectives of a first-in-human single-ascending-dose study and 3 multiple-ascending-dose studies were to characterize the pharmacokinetics, safety, and tolerability of cenobamate after single-dose and multiple-dose administration in healthy subjects. The 4 randomized, placebo-controlled, double-blind studies were conducted in 210 healthy subjects receiving single (5 to 750 mg) or multiple (50 to 600 mg/day) oral doses of cenobamate or placebo using capsule formulation. Safety assessments included treatment-emergent adverse events (TEAEs) and laboratory evaluations. Maximum plasma concentrations of cenobamate were observed between 0.8 and 4.0 hours after oral administration. Cmax increased in a dose-proportional manner for single- and multiple-dose administration across all tested doses. Although the AUC of cenobamate increased in a more than dose-proportional manner after single-dose administration, a dose-proportional increase in cenobamate AUCτ was observed after multiple dosing from 50 to 500 mg/day. Cenobamate exhibited low oral clearance (decreasing from approximately 1.4 to 0.50 L/h with dose increase) and long terminal half-life (range, approximately 30 to 76 hours with increasing dose). Steady-state was attained after approximately 2 weeks, and the accumulation ratio was approximately 5 over the 50 to 300 mg/day range. The pharmacokinetic characteristics of cenobamate are consistent with once-daily dosing. Most TEAEs were mild in severity, 2 serious TEAEs were reported, and no deaths occurred across all studies. Except for multiple daily doses of 600 mg, all doses were generally well tolerated.

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

Use of cenobamate for the treatment of focal epilepsy: an Italian expert opinion paper. [2023] Cenobamate is a new antiseizure medication (ASM) recently introduced in the USA for the treatment of adults with focal-onset seizures. In March 2021, the European Commission authorized its use for the adjunctive treatment of focal-onset seizures with or without secondary generalization (focal seizures with or without progression to bilateral tonic-clonic seizures, according to current ILAE terminology) in adults with epilepsy not adequately controlled despite the treatment with at least two ASMs.