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

Sponsor
SK Life Science, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04791553
Collaborator
(none)
16
Enrollment
2
Locations
2
Arms
10.6
Anticipated Duration (Months)
8
Patients Per Site
0.8
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or DiseaseIntervention/TreatmentPhase
Phase 1

Detailed Description

This is a Phase 1, multi-center, open-label, non-randomized, parallel group PK and safety study of a single oral dose of cenobamate in male and female subjects with normal hepatic function (Group 1, n = 8) and those with severe hepatic impairment (Group 2, n = 8).

The study consists of a 28-day screening period, followed by single dose administration of cenobamate (200mg) on Day 1, an assessment period of 35 days and follow-up visit. All subjects will be confined to the clinical site from Day -1 (the day before dosing) until Day 5. Outpatient visits will be performed regularly until Day 35. The follow-up visit will occur on Day 40 (±1 day).

Study Design

Study Type:
Interventional
Anticipated Enrollment :
16 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
A Phase 1, Open-Label, Pharmacokinetic, Safety and Tolerability Study of a Single Oral Dose of Cenobamate (YKP3089) in Subjects With Normal Hepatic Function and Subjects With Severe Hepatic Impairment
Actual Study Start Date :
Jun 17, 2021
Anticipated Primary Completion Date :
Apr 7, 2022
Anticipated Study Completion Date :
May 5, 2022

Arms and Interventions

ArmIntervention/Treatment
Experimental: Normal Hepatic Function

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
Cenobamate (YKP3089) is a small molecule approved in the United States (US) for the treatment of partial onset seizures (POS) in adult patients.
Other Names:
  • YKP3089
  • Experimental: Hepatic Impairment

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

    Drug: Cenobamate
    Cenobamate (YKP3089) is a small molecule approved in the United States (US) for the treatment of partial onset seizures (POS) in adult patients.
    Other Names:
  • YKP3089
  • Outcome Measures

    Primary Outcome Measures

    1. Cmax [40 days]

      Maximum observed plasma concentration of cenobamate

    2. Area Under the Concentration Curve to last measurable concentration [40 days]

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

    3. Area Under the Concentration Curve from 0 to infinity [40 days]

      AUC from time 0 extrapolated to infinity

    Secondary Outcome Measures

    1. Incidence of Treatment-Emergent Adverse Events [40 days]

      To evaluate the safety and tolerability of cenobamate (Oral Dose of 2x100 mg tablets) administered to matching groups with normal and impaired hepatic function incidence of treatment-emergent adverse events will be monitored.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:
    • All Subjects
    1. Able to understand and willing to sign the ICF and able to comply with the study restrictions

    2. Adult male or female subjects age 18 to 75 years, inclusive, at the time of informed consent

    3. BMI 18.0 - 35.0 kg/m2, inclusive, where BMI (kg/m2) = body weight (kg) / height2 (m2) at Screening

    4. Female subjects of childbearing potential willing to use an acceptable form of birth control, as outlined in Section 12.1.9

    5. 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)

    1. 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

    2. 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)

    1. Subjects with normal hepatic function as judged by the Investigator

    2. 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

    Exclusion Criteria:
    • All subjects
    1. 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)

    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

    3. History of or present epileptic episodes or suicidal attempts

    4. Documented congenital QT syndrome

    5. Corrected QT interval (QTc) using Fridericia correction (QTcF) at Screening or predose > 450 ms or < 350 ms

    6. Unstable ischemic heart disease or severe heart failure (New York Heart Association Class III or IV)

    7. 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

    8. Primary biliary cirrhosis

    9. 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

    10. History of AED-associated rash that involved conjunctiva or mucosae

    11. History of more than one non-serious drug-related hypersensitivity reaction that required discontinuation of the medication

    12. Known hypersensitivity or previous intolerance to cenobamate or any of its excipients

    13. 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

    14. Acute illness within 14 days prior to study drug administration unless mild in severity and approved by the Investigator and Sponsor's medical representative

    15. Active infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

    16. Presence of active infection requiring antibiotics

    17. Concomitant use of medications known to be linked with DRESS syndrome (including carbamazepine, lamotrigine, phenytoin, any sulfonamide [e.g., sulfasalazine, dapsone, sulfamethoxazole], minocycline and nevirapine, abacavir) should be excluded at least 4 weeks prior to dosing and up to 4 weeks post cenobamate dosing

    18. Use of any prescription or non-prescription drugs, including over-the-counter medication, non-routine vitamins and herbal products within 2 weeks prior to study drug administration unless discussed and agreed with the Sponsor's medical representative in writing (Medication used to treat TEAEs does not lead to a compulsory exclusion of subjects)

    19. Ingestion of alcohol within 72 hours prior to study drug administration and during inhouse period. Outside the in-house period, regular alcohol consumption below 24 units for males and 17 units for females per week (1 unit equals 250 mL of beer, 75 mL of wine or 25 mL of spirits) is allowed

    20. Active smokers within the last 6 months

    21. Consumption of an average of more than 5 servings (240 mL per serving) per day of coffee, cola, or other caffeinated beverage before screening. Subjects may not consume any caffeinated beverages from 48 hours prior to dosing until the end of the in-house stay on Day 5.

    22. Participation in a clinical study involving administration of either an investigational or a marketed drug within 2 months or 7 half-lives (whichever is longer) before Screening

    23. Donation or loss of more than 450 mL blood during the 3 months before the start of Screening

    24. Female subjects who are pregnant, nursing, or planning to become pregnant during the study

    25. Clinically significant renal disease (creatinine clearance [CLCr] < 60 mL/min as calculated by the Cockcroft-Gault formula at Screening)

    26. Positive serology for human immunodeficiency virus antibodies (anti-HIV-1/2) at Screening.

    27. Positive urine drug screen (if not due to concomitant medication) or alcohol breath test at Screening and/or Day -1

    28. Legal incapacity or limited legal capacity

    29. Consumption of grapefruit or grapefruit-containing products within 48 hours before Study Day 1 and during the PK sampling period.

    Hepatically-impaired Subjects (in addition)

    1. History of esophageal bleeding within the last 3 months prior to study drug administration.

    2. Severe hepatic encephalopathy (Grade > 2) or degree of central nervous system (CNS) impairment which the Investigator considers sufficiently serious to interfere with the informed consent, the conduct, the completion, or the results of this trial, or constitutes an unacceptable risk to the subject

    3. Has had clinical exacerbation of liver disease within 14 days before study drug administration (e.g., abdominal pain, ascites, nausea, vomiting, anorexia, fever, or worsening of laboratory results related to hepatic function)

    4. Has evidence of acute viral hepatitis within 1 month before Day -1

    5. Has evidence of severe or acute renal failure

    6. History of drug or alcohol abuse within 3 months prior to dosing

    7. Any significant change in chronic treatment medication within 14 days before inclusion

    8. Any medical condition other than hepatic impairment which might alter the drug metabolism

    9. Have used any drugs known to significantly affect hepatic metabolism within 28 days, or is unable or unwilling to forgo the use of such products throughout the study

    10. Has evidence of hepato-renal syndrome

    11. Have acute, fulminant alcoholic hepatitis, determined either clinically or by histology, hepatoma or metastatic disease of the liver

    12. History of liver transplantation

    13. Advanced ascites and ascites which require emptying and albumin supplementation, as judged by the Investigator

    14. Hemoglobin concentration < 105 g/L

    Healthy Subjects (in addition)

    1. Any clinically unstable, uncontrolled medical condition, which in the opinion of the Investigator would preclude the subject participation to the study

    2. Positive serology for HBsAg or anti-HCV

    3. History of any illness or condition that, in the opinion of the Investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject

    4. Illness within 5 days before the start of study drug dosing ("illness" is defined as an acute [serious or non-serious] condition [e.g., the flu or the common cold])

    5. History of drug abuse within the last 2 years prior to study drug administration

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Centrum Badan Klinicznych Piotr Napora lekarze sp.p.,WrocławPoland51-162
    2Summit Clinical Research s.r.o.BratislavaSlovakia83101

    Sponsors and Collaborators

    • SK Life Science, Inc.

    Investigators

    • Study Chair: Janice Laramy, PhD, PharmD, SK Life Science, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    SK Life Science, Inc.
    ClinicalTrials.gov Identifier:
    NCT04791553
    Other Study ID Numbers:
    • YKP3089C038
    First Posted:
    Mar 10, 2021
    Last Update Posted:
    Feb 17, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Feb 17, 2022