Safety Study of Cenobamate in Subjects With Normal Hepatic Function and Subjects With Severe Hepatic Impairment

NCT04791553 | Completed Phase 1 FDA Drug

• 1 other identifier: YKP3089C038
• Study Type: interventional
• Target: 15
• Locations: 2 countries
• Sites: 2

Brief Summary

This study is designed investigate the effect of severe hepatic impairment on the pharmacokinetics (PK) of cenobamate.

Conditions

Hepatic Impairment

Outcome Measures

Primary Outcomes (3)

• Cmax

  Maximum observed plasma concentration of cenobamate

  40 days

• Area Under the Concentration Curve to last measurable concentration

  AUC from the time of dosing to the time of the last measurable concentration of cenobamate

  40 days

• Area Under the Concentration Curve from 0 to infinity

  AUC from time 0 extrapolated to infinity

  40 days

Secondary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events

  40 days

Study Arms (2)

Normal Hepatic Function

EXPERIMENTAL

Group 1 single oral dose of 200 mg (2 x 100 mg tablet) cenobamate given to Matching healthy subjects with normal hepatic function

Drug: Cenobamate

Hepatic Impairment

EXPERIMENTAL

Group 2 single oral dose of 200 mg (2 x 100 mg tablet) cenobamate given to subjects with severe hepatic impairment

Drug: Cenobamate

Interventions

Cenobamate DRUG

Cenobamate (YKP3089) is a small molecule approved in the United States (US) for the treatment of partial onset seizures (POS) in adult patients.

Also known as: YKP3089

Hepatic Impairment; Normal Hepatic Function

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All Subjects
• Able to understand and willing to sign the ICF and able to comply with the study restrictions
• Adult male or female subjects age 18 to 75 years, inclusive, at the time of informed consent
• BMI 18.0 - 35.0 kg/m2, inclusive, where BMI (kg/m2) = body weight (kg) / height2 (m2) at Screening
• Female subjects of childbearing potential willing to use an acceptable form of birth control, as outlined in Section 12.1.9
• Male subjects with female partners of childbearing potential may be enrolled if they, use an acceptable form of birth control, as outlined in Section 12.1.9
• Hepatically-impaired Subjects (in addition)
• Diagnosis of cirrhosis due to parenchymal liver disease, which is confirmed and documented by at least one of the following: medical history, physical examination, hepatic ultrasound, computed tomography (CT) scan, magnetic resonance imaging (MRI), and/or liver biopsy
• Stable hepatic impairment (Child-Pugh score consistent with severe hepatic impairment), defined as no clinically significant change in disease status, as judged by the Investigator
• Healthy Subjects (in addition)
• Subjects with normal hepatic function as judged by the Investigator
• Judged to be in good health in the opinion of the Investigator on the basis of a medical evaluation that reveals the absence of any clinically relevant abnormality (including a physical examination, medical history, ECG, vital signs, and the results of biochemistry, coagulation and hematology tests and urinalysis carried out at Screening) or Subject has a stable disease (e.g., hypertension, hyperlipidemia, diabetes mellitus, hyperthyreosis) under medical control (i.e., adequate treatment), and does not show clinically relevant abnormalities that are not in line with the underlying disease

You may not qualify if:

• All subjects
• Clinically relevant abnormal medical history, abnormal findings on physical examination, vital signs, ECG, or laboratory tests at Screening that the Investigator judges as likely to interfere with the objectives of the trial or the safety of the volunteer except for conditions associated with hepatic impairment in subjects with compromised hepatic function (Group 2)
• Any surgical or medical condition that may significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study
• History of or present epileptic episodes or suicidal attempts
• Documented congenital QT syndrome
• Corrected QT interval (QTc) using Fridericia correction (QTcF) at Screening or predose \> 450 ms or \< 350 ms
• Unstable ischemic heart disease or severe heart failure (New York Heart Association Class III or IV)
• Uncontrolled treated/untreated hypertension (defined as a mean of 3 repeated measurements for systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 105 mmHg); current or documented history of repeated clinically significant hypotension
• Primary biliary cirrhosis
• Subject has a history of any serious drug-induced hypersensitivity reaction (including, but not limited to, Stevens Johnson syndrome, toxic epidermal necrolysis, or Drug Reaction with Eosinophilia and Systemic Symptoms \[DRESS\]) or any drug-related rash requiring hospitalization
• History of AED-associated rash that involved conjunctiva or mucosae
• History of more than one non-serious drug-related hypersensitivity reaction that required discontinuation of the medication
• Known hypersensitivity or previous intolerance to cenobamate or any of its excipients
• History of cancer (judged not to be in full remission) or presence of cancer (except basal cell skin cancer or squamous cell skin cancer) as judged by the Investigator
• Acute illness within 14 days prior to study drug administration unless mild in severity and approved by the Investigator and Sponsor's medical representative

Sponsors & Collaborators

• SK Life Science, Inc.: lead

Study Sites (2)

Centrum Badan Klinicznych Piotr Napora lekarze sp.p.,

Wroclaw, 51-162, Poland

Location

Summit Clinical Research s.r.o.

Bratislava, 83101, Slovakia

Location

MeSH Terms

Interventions

Cenobamate

Study Officials

• Janice Laramy, PhD, PharmD

  SK Life Science, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2021
• First Posted: March 10, 2021
• Study Start: June 17, 2021
• Primary Completion: November 15, 2022
• Study Completion: August 11, 2023
• Last Updated: March 28, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1); SL (1)