Open-label Study of Cenobamate Monotherapy in Adult Subjects With Newly Diagnosed or Recurrent Partial-Onset Epilepsy

NCT06453213 | Active Not Recruiting Phase 4 FDA Drug

• 1 other identifier: YKP3089C049
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 19

Brief Summary

Cenobamate (YKP3089) is a small molecule approved in the United States (US), Europe and several other countries around the world for the treatment of Partial-Onset (focal) seizures in adult subjects (≥18 years of age). In the US it is approved for use as monotherapy, however, there is little clinical data assessing its use as monotherapy in adults with POS. This study is designed to explore the effectiveness of doses of 100 mg/day and 200 mg/day as monotherapy in adult subjects with newly diagnosed or recurrent POS/focal onset epilepsy.

Conditions

Focal Onset Seizure

Outcome Measures

Primary Outcomes (1)

• Seizure-freedom during the 26-week Maintenance Phase of the 100 mg/day Treatment Period

  The number (percentage) of subjects with POS who achieved seizure-freedom during the 26-week Maintenance Phase of the 100 mg/day Treatment Period.

  32 weeks

Secondary Outcomes (4)

• Seizure freedom during each of the 26-week Maintenance Phases

  60 weeks

• Time to first seizure onset

  52 weeks

• Time to withdrawal from the study

  86 weeks

• Number (percentage) of subjects with POS who achieved seizure freedom during the 52-week treatment

  52 weeks

Other Outcomes (1)

• Seizure-freedom rate/time to seizure by POS type

  86 weeks

Study Arms (1)

Cenobamate

EXPERIMENTAL

All enrolled subjects will automatically participate in the Cenobamate arm since this is a single-arm study.

Drug: Cenobamate

Interventions

Cenobamate DRUG

The 100 mg/ day Treatment Period includes a 6-week Titration Phase and a 26-week Maintenance Phase. During the Titration Phase subjects will be treated with cenobamate 12.5 mg/day for two weeks, 25 mg/day for two weeks and 50 mg/day for two weeks. Subjects tolerating cenobamate at the end of the Titration Phase will continue treatment with 100 mg/day in the Maintenance Phase for 26 weeks. If the subject does not experience a certain type of seizure in the 100 mg/day Maintenance Phase, he/she can enter the Optional Extension Period (100 mg/day). The 200 mg/day treatment period consists of a 2-week Titration Phase and a 26-week Maintenance Phase. During the 2-week Titration Phase, subjects will receive cenobamate 150 mg/day before entering the 26-week 200 mg/day Maintenance Phase. If the subject does not experience a certain type of seizure during the 200 mg/day Maintenance Phase, he/she can enter the 26 week Optional Extension Period (200 mg/day).

Cenobamate

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be considered reliable and willing to be available for the study period and are able to record seizures and report adverse events (AEs) himself/herself or have a caregiver who can record seizures and report AEs for them.
• Male or female subjects 18-74 years of age with a diagnosis of partial-onset seizures (POS) according to the 2017 ILAE Classification of Epileptic Seizures. Diagnosis will be established by clinical history and an electroencephalogram (EEG) consistent with POS. Subjects with a normal EEG could be included provided they met the other diagnostic criteria according to clinical history.
• Subjects who are newly diagnosed or have recurrent epilepsy and have experienced:
• At least 2 unprovoked seizures (at least \>24 hours apart) within the 1 year prior to Day 1 of the Treatment Period, of which, at least 1 unprovoked seizure (but below 20 seizures) occurred in the 12 weeks prior to Day 1 of the Treatment Period.
• unprovoked seizure within the 12 weeks prior to Day 1 of the Treatment Period with concomitant information to support an increased risk (\>60%) of a second seizure. In the absence of clear information about recurrence risk, or even knowledge of such information, the default definition of epilepsy originates at the second unprovoked seizure.
• Subjects who are newly diagnosed and have been prescribed a low dose of 1 ASM for ≤12 weeks can be included if the other ASM can be safely down-titrated/discontinued per Investigator discretion within 6 weeks after the 1st dose of cenobamate. For subjects with recurrent epilepsy, they must have relapsed at least 6 months after the end of the last ASM treatment but can have been prescribed a low dose of 1 ASM for ≤12 weeks if the other ASM can be safely down-titrated/discontinued per Investigator discretion within 6 weeks after the 1st dose of cenobamate.
• Female subjects are either not of childbearing potential, defined as premenarchal, postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), if of childbearing potential, must comply with an acceptable method of birth control during the study, for at least 4 weeks prior to study entry and for 2 weeks after last dose of study drug.
• Subject and/or caregiver(s)/legal representative must be willing and able to give informed assent/consent for participation in the study.
• Subject and their caregiver must be willing and able (in the investigator's opinion) to comply with all study requirements.

You may not qualify if:

• Subjects who have only simple partial-onset seizures (focal aware seizures) without motor signs.
• Subjects who have seizure clusters where individual seizures cannot be counted.
• Subjects who present with or have a history of Lennox-Gastaut syndrome.
• Subjects who have a history of status epilepticus that required hospitalization within 1 year prior to Day 1 of the Treatment Period.
• Subjects who have a history of psychogenic non-epileptic seizures within 2 years prior to Day 1 of the Treatment Period.
• Subjects who have a history of active suicidal ideation within the last 6 months or suicide attempt within 2 years prior to Day 1 of Treatment Period.
• Evidence of clinically significant disease (eg, cardiac, respiratory, gastrointestinal, psychiatric, other neurological) that in the opinion of the investigator(s) could affect the subject's safety or interfere with the study assessments.
• History of Familial Short QT syndrome or prior subject diagnosis of Short QT syndrome.
• Evidence of clinically significant active renal or hepatic disease.
• Subjects taking a strong CYP3A inducer such as phenytoin, phenobarbital, carbamazepine, or rifampin within 12 weeks prior to the Pretreatment Period unless emergency care was needed due to the subject experiencing status epilepticus, uncontrolled seizures, or clusters of seizures.
• Subjects who are taking more than one of the following centrally acting drugs: antipsychotic, antidepressant, or anxiolytic. The dose should be stable for the 12 weeks prior to the Pretreatment Period.
• Subjects who have a history of any type of surgery for brain or central nervous system within 1 year prior to the Pretreatment Period.
• Subjects who have a history of receiving any ASM (including ASM used as rescue treatment and ASMs used for indications other than epilepsy) for more than 12 weeks in total within 6 months prior to Day 1 of the Treatment Period.
• Subjects who have used intermittent rescue medicine on 2 or more occasions within 12 weeks before the Pretreatment Period (1 to 2 doses over a 24-hour period considered one-time rescue).
• Subjects who have a history of receiving any ASM polytherapy (\> 2 ASMs taken concurrently) during a previous episode of epilepsy.

Sponsors & Collaborators

• SK Life Science, Inc.: lead

Study Sites (19)

Arizona Neuroscience Research

Phoenix, Arizona, 85032, United States

Location

Center For Neurosciences

Tucson, Arizona, 85718, United States

Location

Clinical Trials Inc

Little Rock, Arkansas, 72205, United States

Location

Neuro Pain Medical Center

Fresno, California, 93710, United States

Location

Hoag Physician Partners

Newport Beach, California, 92663, United States

Location

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

Yale School of Medicine - Yale-New Haven Hospital

New Haven, Connecticut, 06519, United States

Location

Elite Clinical Research

Miami, Florida, 33144, United States

Location

Knight Neurology

Rockledge, Florida, 32955, United States

Location

Consultants In Epilepsy and Neurology

Boise, Idaho, 83702, United States

Location

Bluegrass Epilepsy Research LLC

Lexington, Kentucky, 40504, United States

Location

Louisiana State University Health Sciences

Shreveport, Louisiana, 71103, United States

Location

John Hopkins Epilepsy Center

Baltimore, Maryland, 21287, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Wayne Neurology PLC

Plymouth, Michigan, 48170, United States

Location

University of Missouri Health Care

Columbia, Missouri, 65212, United States

Location

NY Neurology Associates

New York, New York, 10003, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

DHR Health Institute for Research and Development

Edinburg, Texas, 78539, United States

Location

MeSH Terms

Conditions

Seizures

Interventions

Cenobamate

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2024
• First Posted: June 11, 2024
• Study Start: October 14, 2024
• Primary Completion (Estimated): May 26, 2027
• Study Completion (Estimated): July 9, 2027
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

US (19)