The main aim of this study is to understand how moderate and severe liver impairment (based on the Child-Pugh classification) affects the body's processing of a single dose of 10 mg maximum of palovarotene, compared to healthy participants with normal liver function. The study will also assess the safety and tolerability of the single dose of palovarotene. Participants will be enrolled in stages and divided into three groups based on their liver function: * Group 1: Healthy participants with normal liver function * Group 2: Participants with moderate liver impairment * Group 3: Participants with severe liver impairment (only enrolled if Group 2 results are safe and acceptable) Blood samples will be taken to assess how the drug binds to proteins in the blood. Participants will undergo various safety checks and procedures. Participants will stay in the clinical unit until Day 5 for these assessments and will return on Day 10 for a final visit.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
32
A single dose of maximum 10 mg of palovarotene will be administered orally on Day 1 to healthy control participants with normal hepatic function
A single 10 mg dose of palovarotene will be administered orally on Day 1 to Moderate hepatic impaired participants (Child-Pugh class B)
A single 10 mg dose of either 5 mg or 10 mg of palovarotene will be administered orally on Day 1 to Severe hepatic impaired participants (Child-Pugh class C).
ERG - Clinical Pharmacology of Miami
Miami, Florida, United States
RECRUITINGOrlando Clinical Research Center
Orlando, Florida, United States
RECRUITINGAmerican Research Corporation/Texas Liver Institute
San Antonio, Texas, United States
RECRUITINGPinnacle Clinical Research
San Antonio, Texas, United States
RECRUITINGMaximum observed plasma drug concentration (Cmax)
Measure of maximum observed plasma drug concentration (Cmax) (total and unbound) over 96 hours after dosing
Time frame: Over 96 hours postdose
Unbound fraction of drug in plasma (fu)
Measure of maximum observed plasma drug concentration (Cmax) (total and unbound) over 96 h after dosing
Time frame: Over 96 hours postdose
Time to maximum observed plasma concentration (Tmax)
Measure of AUC from time 0 to infinity (AUC0-∞) (total and unbound)
Time frame: Over 96 hours postdose
Area under the plasma concentration-time curve (AUC) from time 0 to infinity (AUC0-∞)
Measure of AUC from time 0 to infinity (AUC0-∞) (total and unbound)
Time frame: Over 96 hours postdose
AUC from 0 to time t corresponding to the last quantifiable concentration (AUC0-tlast)
Measure of AUC from 0 to time t corresponding to the last quantifiable concentration (AUC0-tlast) (total and unbound)
Time frame: Over 96 hours postdose
Apparent terminal elimination half life (T1/2)
Measure of apparent terminal elimination half-life over 96 hours post-dose
Time frame: Over 96 hours postdose
Apparent terminal elimination rate constant (λz).
Measure of apparent terminal elimination rate constant (λz) over 96 hours post-dose
Time frame: Over 96 hours postdose
Percentage of participants with Adverse Events (AEs)
An Adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Time frame: From Baseline to Day 10
Percentage of Participants with clinically significant changes from baseline in Laboratory Parameters
Clinically significant change in laboratory parameters will be reported. The clinical significance will graded by the investigator.
Time frame: At Day 2, Day 5 and Day 10
Percentage of participants with clinically significant change from baseline in physical examinations
Clinically significant changes in physical examinations will be reported. The clinical significance will be graded by the investigator.
Time frame: At Day 1, 2 and 3, Day 5 and Day 10
Percentage of Participants With Clinically Significant Changes from baseline in Vital Signs
Clinically significant changes in vital signs will be reported. The clinical significance will be graded by the investigator.
Time frame: At Day 1, 2 and 3, Day 5 and Day 10
Percentage of participants with clinically significant change from baseline in 12-lead Electrocardiogram (ECG) readings
Time frame: At Day 1, 2 and 3, Day 5 and Day 10
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