Randomized, Double-blind Study to Evaluate Efficacy and Safety of Cenobamate Adjunctive Therapy in POS

NCT04557085 | Unknown Phase 3 DMC

• 1 other identifier: YKP3089C035
• Study Type: interventional
• Target: 540
• Locations: 3 countries
• Sites: 3

Brief Summary

This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, adjunctive therapy study in subjects with POS, with optional OLE. The study consists of 4 periods as follows: An 8-week of Screening/Baseline Period, 24-week of Double-blind Treatment Period (including a 18-week Titration Phase and 6-week Maintenance Phase), 52-week of Open-label Extension (OLE) Period (applicable for subjects who participate in the OLE) and up to 5-week of End of Study (EOS) Follow-up Period. The purpose of this study is to evaluate the efficacy and safety of 100, 200 and 400 mg/day of cenobamate as adjunctive therapy compared with placebo in subjects with partial onset seizures (POS). The study will also evaluate the long-term safety and tolerability of cenobamate adjunctive therapy in subjects with POS who have completed the double-blind treatment period.

Conditions

Partial Seizure; Focal Seizure

Outcome Measures

Primary Outcomes (1)

• Percent change from baseline in seizure frequency (seizure rate per 28-day interval) of all simple partial motor, complex partial, or secondarily generalized seizures during the Maintenance Phase.

  per 28 days during 6 week maintenance phase

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Cenobamate 100 mg/day

EXPERIMENTAL

Cenobamate 100 mg/day

Drug: Cenobamate

Cenobamate 200 mg/day

EXPERIMENTAL

Cenobamate 200 mg/day

Drug: Cenobamate

Cenobamate 400 mg/day

EXPERIMENTAL

Cenobamate 400 mg/day

Drug: Cenobamate

Interventions

Cenobamate DRUG

Cenobamate tablets

Cenobamate 100 mg/day; Cenobamate 200 mg/day; Cenobamate 400 mg/day

Placebo DRUG

Matching placebo tablets

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligible subjects must meet all of the following criteria to be enrolled in the study:
• Male or female subject and age 18 to 70 years inclusive at the time of signing the informed consent
• Weight at least 35 kg
• Written informed consent signed by the subject prior to entering the study in accordance with the ICH GCP guidelines. For subjects who lack the capacity, consent will be obtained from the parent/legal guardian. For all underaged subjects according to the specific laws of the country, both the written consent of the subject and the consent of the parent/legal guardian will be obtained.
• A diagnosis of partial onset seizures according to the International League Against Epilepsy's Classification of Epileptic Seizures (1981). Diagnosis should have been established by clinical history and an electroencephalogram (EEG).
• EEG performed within 5 years prior to Visit 1 that is consistent with localization related epilepsy; normal interictal EEGs will be allowed provided that the subject meets the other diagnosis criterion (i.e., clinical history). For chronic patients for which the current diagnosis is not very clear, additional EEG results older than 5 years but within 10 years may be used for final confirmation of epilepsy diagnosis.
• Need additional antiepileptic drug (AED) treatment despite having been treated with at least one AED for the last 2 years.
• During the 8-week Screening/Baseline Period, subjects must have at least 8 partial seizures including only simple partial seizures with motor component, complex partial seizures, or secondarily generalized seizures without a seizure-free interval of greater than 25 days any time during the 8-week period. Subjects must have at least 3 of these partial seizures during each of the two consecutive 4-week segments of the Screening/Baseline Periods, respectively.
• Currently on stable antiepileptic treatment regimen:
• Subject must have been receiving stable doses of 1 to 3 AEDs for at least 4 weeks prior to Visit 1 to be continued unchanged throughout the Double-blind Treatment Period.
• Vagal nerve stimulator (VNS) or deep brain stimulator (DBS) will not be counted as an AED; however, the parameters must remain stable for at least 4 weeks prior to Visit 1 and during the study. VNS or DBS must have been implanted at least 5 months prior to Visit 1.
• The daily use of benzodiazepines (except for diazepam) for epilepsy, or for anxiety or sleep disorder, will be counted as 1 AED and must be continued unchanged throughout the study. Therefore, only a maximum of 2 additional approved AEDs will be allowed.
• Subjects receiving felbamate as a concomitant AED must meet the following criteria:
• i. Two-year history of felbamate use and a history of a fixed dosing regimen for a minimum of 60 days prior to Visit 1 ii. No prior or known history of hepatotoxicity or hematologic disorder due to felbamate
• Computed tomography (CT) or magnetic resonance imaging (MRI) scan performed within the past 5 years that ruled out a progressive cause of epilepsy. If brain imaging has not been performed within the past 5 years, a CT scan must be performed prior to randomization. For chronic patients for which the current diagnosis is not very clear, additional CT or MRI results older than 5 years but within 10 years may be used for final confirmation of epilepsy diagnosis.

You may not qualify if:

• Female subjects who are pregnant (or planning to become pregnant during the study), lactating or breast-feeding
• History of non-epileptic or psychogenic seizures
• Presence of only non-motor simple partial seizures or primary generalized epilepsies
• History of seizure clusters (episodes lasting less than 30 minutes in which multiple seizures occur with such frequency that the initiation and completion of each individual seizure cannot be distinguished) within 6 months prior to Visit 1
• Presence or previous history of Lennox-Gastaut syndrome
• Scheduled epilepsy surgery within 8 months of Visit 1
• Evidence of any clinically significant laboratory abnormalities or disease (e.g., psychiatric, behavioral problems, cardiac, respiratory, gastrointestinal, hepatic \[liver transaminases, ALT or AST, more than twice the upper limit of normal (ULN) or total or direct bilirubin not within normal limits\], or renal disease) that, in the opinion of the Investigator, could affect subject's safety or conduct of the study.
• Any clinically significant active central nervous system (CNS) infection, demyelinating disease, degenerative neurologic disease, or any CNS disease deemed to be progressive during the course of the study that may confound the interpretation of the study results
• Presence of psychotic disorders and/or unstable recurrent affective disorders evident by use of antipsychotics; presence or recent history (within 6 months) of major depressive episode
• Use of intermittent rescue benzodiazepines more than once per month (1 to 2 doses in a 24-hour period is considered as 1 rescue) in the 1-month period prior to Visit 1
• Current or recent use (within 30 days prior to Visit 1) of any of the following medications: diazepam/phenytoin/phenobarbital (or metabolites of these drugs), clopidogrel, fluvoxamine, amitriptyline, clomipramine, bupropion, methadone, ifosfamide, cyclophosphamide, efavirenz, natural progesterone, or traditional Chinese/herbal medicines indicated for neurological system
• Current or recent (within 5 months prior to Visit 1) use of vigabatrin or ezogabine. Subjects with a prior history of treatment with vigabatrin must have documentation showing no evidence of a vigabatrin associated clinically significant abnormality in a visual perimetry test. Subjects with a prior history of treatment with ezogabine should have no evidence of retinal abnormalities with funduscopic features similar to those seen in retinal pigment dystrophies.
• Previous exposure to cenobamate
• Participation in any other trials involving an investigational product or device within 30 days prior to Visit 1
• History of alcoholism, drug abuse, or drug addiction within the past 2 years prior to Visit 1 as assessed by the Investigator

Sponsors & Collaborators

• SK Life Science, Inc.: lead

Study Sites (3)

Site 3

Shanghai, China

Location

Site 2

Tokyo, Japan

Location

Site 1

Seoul, South Korea

Location

Related Publications (1)

• Wu X, Chen L, Choe E, Heo K, Hong SB, Iida K, Jeon YH, Jung J, Kamin M, Kawai K, Kim JH, Kim MW, Lee SK, Misra SN, Park J, Rosenfeld WE, Wang T, Yamamoto T, Yu P, Ferrari L. Efficacy of adjunctive cenobamate by focal seizure subtypes: a randomized, double-blind, placebo-controlled, multicenter study in a multinational Asian population. Seizure. 2025 Dec;133:43-51. doi: 10.1016/j.seizure.2025.09.021. Epub 2025 Sep 29.

  PMID: 41101116 DERIVED

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 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2020
• First Posted: September 21, 2020
• Study Start: March 8, 2021
• Primary Completion: February 1, 2024
• Study Completion: March 1, 2025
• Last Updated: October 10, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1); KR (1); CN (1)