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Hepatic ImpairmentPhase 1NCT04791553

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

A Phase 1 study testing Cenobamate in people with Hepatic Impairment, run by SK Life Science, Inc. at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 18 to 75 yearsHealthy volunteers can take part
Conditions the study is for
Hepatic Impairment
What is being tested?
Cenobamate
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
2 sitesin 2 countries
Study dates
17 Jun 2021to 11 Aug 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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
  • Active infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
  • Presence of active infection requiring antibiotics
  • 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
  • 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)
  • 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
  • Active smokers within the last 6 months
  • 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.
  • 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
  • Donation or loss of more than 450 mL blood during the 3 months before the start of Screening
  • Female subjects who are pregnant, nursing, or planning to become pregnant during the study
  • Clinically significant renal disease (creatinine clearance [CLCr] < 60 mL/min as calculated by the Cockcroft-Gault formula at Screening)
  • Positive serology for human immunodeficiency virus antibodies (anti-HIV-1/2) at Screening.
  • Positive urine drug screen (if not due to concomitant medication) or alcohol breath test at Screening and/or Day -1
  • Legal incapacity or limited legal capacity
  • 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)
  • History of esophageal bleeding within the last 3 months prior to study drug administration.
  • 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
  • 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)
  • Has evidence of acute viral hepatitis within 1 month before Day -1
  • Has evidence of severe or acute renal failure
  • History of drug or alcohol abuse within 3 months prior to dosing
  • Any significant change in chronic treatment medication within 14 days before inclusion
  • Any medical condition other than hepatic impairment which might alter the drug metabolism
  • 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
  • Has evidence of hepato-renal syndrome
  • Have acute, fulminant alcoholic hepatitis, determined either clinically or by histology, hepatoma or metastatic disease of the liver
  • History of liver transplantation
  • Advanced ascites and ascites which require emptying and albumin supplementation, as judged by the Investigator
  • Hemoglobin concentration < 105 g/L
  • Healthy Subjects (in addition)
  • Any clinically unstable, uncontrolled medical condition, which in the opinion of the Investigator would preclude the subject participation to the study
  • Positive serology for HBsAg or anti-HCV
  • 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
  • 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])
  • History of drug abuse within the last 2 years prior to study drug administration

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Poland1 site

  • Centrum Badan Klinicznych Piotr Napora lekarze sp.p.,

    Wroclaw, 51-162

Other trials in Poland

Slovakia1 site

  • Summit Clinical Research s.r.o.

    Bratislava, 83101

Other trials in Slovakia

About this study

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

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

Read the 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).

Being tested
Cenobamate

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CenobamateDrug

    Also called YKP3089

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

Study groups in NCT04791553
Study groupRoleWhat they receive
Normal Hepatic FunctionExperimentalGroup 1 single oral dose of 200 mg (2 x 100 mg tablet) cenobamate given to Matching healthy subjects with normal hepatic function
Receives: Drug: Cenobamate
Hepatic ImpairmentExperimentalGroup 2 single oral dose of 200 mg (2 x 100 mg tablet) cenobamate given to subjects with severe hepatic impairment
Receives: Drug: Cenobamate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Cmax

    Maximum observed plasma concentration of cenobamate

    Measured: 40 days

  2. 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

    Measured: 40 days

  3. Area Under the Concentration Curve from 0 to infinity

    AUC from time 0 extrapolated to infinity

    Measured: 40 days

Secondary outcomes (1)

  1. Incidence of Treatment-Emergent Adverse Events

    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.

    Measured: 40 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Mar 2021
  2. Study start17 Jun 2021
  3. Primary completion15 Nov 2022
  4. Study completion11 Aug 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04791553
Sponsor's protocol ID
YKP3089C038
Status last verified
Mar 2024
First submitted
8 Mar 2021
Last updated
28 Mar 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cenobamate in people with Hepatic Impairment, run by SK Life Science, Inc. at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 51 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Poland, Slovakia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cmax (time frame: 40 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04791553.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2024.

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