Purpose

The objective of this study is to evaluate the pharmacokinetics, safety, and tolerability of one dose of vorasidenib in participants with severe impaired hepatic function compared to participants with normal hepatic function. The study includes a screening phase, a treatment period, and a follow-up period. During the first part of the treatment period, from Day 1 through Day 4, participants will remain in-house in the clinical research unit. In the second part of the treatment period, from Day 5 through Day 43, participants can go home but may also choose to remain in-house. The entire study, including screening and follow-up, will last up to 77 days. Participants may undergo blood tests, heart tests (electrocardiogram (ECG)), vital sign checks, and physical exams.

Conditions

Eligibility

Eligible Ages
Between 18 Years and 75 Years
Eligible Sex
All
Accepts Healthy Volunteers
Yes

Inclusion Criteria

Participants with hepatic impairment: - Diagnosis of cirrhosis due to parenchymal liver disease - Considered to have a Child-Pugh score of 10 to 15, consistent with severe HI, and a documented medical history of liver disease. Participants must be clinically stable (no acute episodes of illness due to deterioration in hepatic function) for at least 1 month prior to screening and are likely to remain stable throughout the study. - Grade 0 or Grade 1 hepatic encephalopathy considered stable per Investigator assessment without exacerbation within the 6 months prior to screening. - Currently on a stable medication regimen, defined as not starting new drug(s) or significantly changing drug dosage(s) within 14 days preceding Day 1. - Non-hepatic abnormal laboratory values must be not clinically significant as judged by the Investigator (or designee) and the study medical monitor. - Anemia secondary to hepatic disease is acceptable if hemoglobin is ≥ 9 g/dL and anemia symptoms are not clinically significant. Platelet count must be ≥ 35,000 platelets. - QT interval corrected for heart rate using Fridericia's formula (QTcF) of ≤ 480 msec. Matched-control participants: - Healthy, with normal hepatic function with a Child-Pugh score below 5. - Resting blood pressure of 90 to 140 mmHg (systolic) and 40 to 90 mmHg (diastolic). - QTcF of ≤ 450 msec. - Participant must match hepatically impaired participants with respect to sex, race, age (±10 years), smoking status (smoke or vape ≤ 10 cigarettes/day), and body mass index (±20%).

Exclusion Criteria

for all participants: - Women of childbearing potential (WOCBP) who are pregnant, lactating, or planning to become pregnant within 90 days after the dose of vorasidenib. - The participant is using hormonal contraceptives - Use of any other investigational drug or device within 30 days (or 5 half-lives if known, whichever is longer) before the dose of vorasidenib - Consumption of any nutrients known to modulate CYP450 enzymes activity (e.g., grapefruit or grapefruit juice, pomelo juice, star fruit, Seville [blood] orange products) within 14 days before vorasidenib administration. - Consumption of alcohol-containing foods or beverages or caffeine- or xanthine-containing foods or beverages (including, but not limited to, teas [including decaffeinated teas], coffees [including decaffeinated coffees], colas [including decaffeinated colas], energy drinks, gum containing caffeine, and chocolate (including foods and beverages containing chocolate) within 48 hours prior to admission - Any history (within 5 years prior to screening) or presence of malignancy, except for adequately treated basal cell and squamous cell carcinoma of the skin - History within the previous 12 months of alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 12 oz beer, 5 oz wine, or 1.5 oz spirits) - In the opinion of the Investigator, the participant is not suitable for entry into the study

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Basic Science
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Participants with Severe Hepatic Impairment (HI)
  • Drug: Vorasidenib 20mg
    Vorasidenib 20mg will be taken by mouth on Day 1
Experimental
Matched-Participants with Normal Hepatic Function
  • Drug: Vorasidenib 20mg
    Vorasidenib 20mg will be taken by mouth on Day 1

Recruiting Locations

Arizona Clinical Trials
Chandler, Arizona 85225
Contact:
Dr. Anita Kohli

Orlando Clinical Research Center
Orlando, Florida 32809
Contact:
Dr. Thomas Marbury

American Research Corporation
San Antonio, Texas 78215
Contact:
Dr. Eric Lawitz

More Details

Status
Recruiting
Sponsor
Institut de Recherches Internationales Servier (I.R.I.S.)

Study Contact

Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies Department
+33 1 55 72 60 00
scientificinformation@servier.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.