What side effects are associated with this type of intervention?

Common treatments for generalized epilepsy that modulate ion channels and enhance inhibitory neurotransmission, such as valproate, gabapentin, and pregabalin, have several known side effects. Valproate can cause nausea, somnolence, tremor, dizziness, weight gain, and hair loss, and is contraindicated in pregnancy due to teratogenicity. Gabapentin may lead to sleepiness, dizziness, and gait unsteadiness, particularly in older adults. Pregabalin's side effects include dizziness, sleepiness, dry mouth, edema, and blurred vision. These side effects should be considered when choosing an appropriate treatment plan.

What prior FDA approvals exist?

Several FDA-approved drugs for the treatment of generalized epilepsy include valproate, lamotrigine, and topiramate. Valproate is often considered a first-line treatment and works by increasing levels of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter. Lamotrigine stabilizes neuronal membranes by inhibiting sodium channels, and topiramate enhances GABA activity while also inhibiting sodium channels and certain types of glutamate receptors. These drugs share some similarities with cenobamate, which modulates ion channels and enhances inhibitory neurotransmission.

What other types of research exist?

Promising novel alternatives to Cenobamate for Generalized Epilepsy patients include: 1) Perampanel, which is a non-competitive AMPA receptor antagonist; 2) Brivaracetam, which binds to synaptic vesicle protein 2A (SV2A); 3) Cannabidiol (CBD), which has a unique mechanism involving multiple pathways; and 4) Fenfluramine, which modulates serotonin pathways and has shown efficacy in Dravet syndrome, a form of epilepsy.

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Cenobamate for Seizures

Phase 3

Recruiting

Research Sponsored by SK Life Science, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Subject experiences at least 5 PGTC seizures in 12 weeks during the Pre-Randomization Period.

Subject has a clinical diagnosis of PGTC seizures in the setting of idiopathic generalized epilepsy.

Must not have

Female subjects who are pregnant, lactating, or breast-feeding.

Subject has a history of status epilepticus that required hospitalization within 12 months prior to Visit 1 (Screening/Baseline).

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 28 days

Awards & highlights

Pivotal Trial

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include tolerability issues that could require adjusting the dosage time from morning to evening or reducing the target dose from 200 mg to 150 mg once reached. Specific side effects are not listed but would typically relate to medication adjustments.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have had at least 5 strong seizures in the last 12 weeks.

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I have been diagnosed with a specific type of seizure due to generalized epilepsy.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am not pregnant, lactating, or breastfeeding.

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

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I have not had thoughts of harming myself at the start or during the study.

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I am allergic to or have had a reaction to cenobamate or its ingredients.

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My platelet count is below 80,000/µL and I am taking valproate.

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I experience seizure clusters that are hard to count or classify.

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I have been diagnosed with partial onset seizures.

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I have been diagnosed with Lennox-Gastaut syndrome.

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I have used vigabatrin recently or plan to start using it during the study.

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I have a short QT syndrome or my ECG shows a QT interval less than 340 msec.

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My kidney function is reduced with a creatinine clearance under 50 mL/min.

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I do not have any serious brain infections or diseases that get worse over time.

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I have had seizures that aren't caused by epilepsy.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 28 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~28 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and 28 days for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Seizure Diary

Side effects data

From 2022 Phase 3 trial • 1345 Patients • NCT02535091

23%

Somnolence

22%

Fatigue

12%

Balance disorder

Nystagmus

Diplopia

Gait disturbance

Nausea

Decreased appetite

Ataxia

Vision blurred

Headache

Pneumonia

Gynaecomastia

Dysarthria

Gastritis

Intervertebral disc protrusion

Intentional overdose

Prostate cancer

Corona virus infection

Arterial haemorrhage

Generalized tonic-clonic seizure

Partial seizures with secondary generalisation

Seizure

Anger

Suicide attempt

Hypovolaemic shock

Forearm fracture

Generalised tonic-clonic seizure

Vomiting

100%

80%

60%

40%

20%

Study treatment Arm

YKP3089 and Phenytoin

YKP3089 and Phenobarbital

YKP3089 and Other AEDs

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: CenobamateExperimental Treatment1 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: PlaceboPlacebo Group1 Intervention

Matching placebo

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cenobamate

2021

Completed Phase 1

~120

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Generalized Epilepsy, such as valproate, lamotrigine, and levetiracetam, work by stabilizing neuronal activity and preventing excessive firing. Valproate increases gamma-aminobutyric acid (GABA) levels, enhancing inhibitory neurotransmission. Lamotrigine inhibits voltage-sensitive sodium channels, reducing excitatory neurotransmitter release. Levetiracetam binds to synaptic vesicle protein SV2A, modulating neurotransmitter release. Cenobamate, similar to these treatments, modulates ion channels and enhances inhibitory neurotransmission, which is crucial for controlling the widespread neuronal hyperactivity characteristic of Generalized Epilepsy. These mechanisms help to reduce seizure frequency and severity, improving patient outcomes.

Felbamate add-on therapy for drug-resistant focal epilepsy.Enhanced glutamatergic transmission reduces the anticonvulsant potential of lamotrigine but not of felbamate against tonic-clonic seizures.