Clinical trial NCT06908954: A Study of the Blood Levels of Palovarotene in Participants With Abnormal Liver Function Compared to Healthy Adult Participants After Intake of a Single Dose
Official title: A Phase I, Open-label, Parallel-group Study to Evaluate the Single-dose Pharmacokinetics of Palovarotene in Male and Female Participants With Moderate and Severe Hepatic Impairment and Matched Participants With Normal Hepatic Function
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Hepatic Impairment
Healthy
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2025-04-03
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Male and female participants must be 18 to 70 years of age (inclusive) at the time of signing informed consent.
* Body weight at least 60.0 kg with body mass index (BMI) within the range of 18.0 and 36.0 kg/m² (inclusive), at screening. BMI of \>36.0 to ≤37.0 may be eligible if participant has ascites scoring 3 points on the C-P criteria.
* Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical trials
* Clinical diagnosis of chronic hepatic disease (stable for more than 3 months) with a documented history of underlying hepatic insufficiency and no acute episodes of illness within 30 days prior to Day -1 (admission) and no significant change in disease status (i.e. up to 1 point in the C-P classification) from screening to Day -1.
* A stable medication regimen, defined as not starting new therapy(ies) or significant changing dosage(s) within 30 days prior to dosing.

Exclusion Criteria:

* Presence or significant history of cardiovascular, respiratory, hepatic (except for the hepatic impairment for those concerned), renal, gastrointestinal, biliary, mucocutaneous, endocrinological, haematological or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs, constituting a risk when taking the study intervention, or interfering with the interpretation of data.
* Lymphoma, leukaemia or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
* Breast cancer within the past 10 years.
* Use of any medications (prescription or over the counter), herbal tea, energy drinks (including natural stimulants), herbal products (e.g. St. John's wort, garlic, milk thistle) or supplements/supratherapeutic doses of vitamins within 14 days prior to Day 1 and through discharge, apart from those approved by the investigator and the sponsor's medical monitor. Those with hepatic impairment may take concomitant medications
* Use of any medications that are moderate or strong inhibitors or inducers of CYP3A4
* Donation or loss (excluding volume drawn at screening or during menses) of more than 250 mL of blood or blood product within 3 months prior to screening. In addition, plan of blood donation within 8 weeks after the last PK sampling.
* Presence of hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to the dose of study intervention.
* Positive hepatitis C antibody test result at screening or within 3 months prior to the dose of study intervention. Note: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled if a confirmatory negative hepatitis C ribonucleic acid (RNA) test is obtained.
* Positive hepatitis C RNA test result at screening or within 3 months prior to the dose of study intervention. Note: Test is optional and participants with negative hepatitis C antibody test are not required to also undergo hepatitis C RNA testing.
* Sensitivity to the study intervention, or components thereof (including inactive ingredients), or drug or other allergy that, in the opinion of the investigator (or medical monitor), contraindicates participation in the study
* Evidence of relevant active disease at screening, including gastroenterological (other than hepatic cirrhosis), cardiac (e.g. myocardial infarction in the past year, angina or congestive heart failure), renal, respiratory, haematological, neuropsychiatric or neoplastic (basal or squamous cell skin cancer is acceptable) disease.
* Acute hepatitis B (positive for HBsAg) or acute hepatitis C (positive for anti-hepatitis C virus (HCV) for a duration of less than 6 months). Note: Participants with chronic HCV (positive for HCV RNA or anti-HCV for more than 6 months) are eligible for enrolment, if stable, as assessed by the investigator.
* Primary sclerosing cholangitis or preliminary diagnosed biliary obstruction at screening.
* Current or chronic history of liver disease. This includes (but is not limited to hepatitis virus infections), drug- or alcohol-related liver disease, non-alcoholic steatohepatitis, autoimmune hepatitis, hemochromatosis, Wilson's disease, α-1 antitrypsin deficiency, primary biliary cholangitis, primary sclerosing cholangitis, or any other liver disease considered clinically significant by the investigator.

Primary outcomes:
measure: Maximum observed plasma drug concentration (Cmax)
timeFrame: Over 96 hours postdose
measure: Unbound fraction of drug in plasma (fu)
timeFrame: Over 96 hours postdose
measure: Time to maximum observed plasma concentration (Tmax)
timeFrame: Over 96 hours postdose
measure: Area under the plasma concentration-time curve (AUC) from time 0 to infinity (AUC0-∞)
timeFrame: Over 96 hours postdose
measure: AUC from 0 to time t corresponding to the last quantifiable concentration (AUC0-tlast)
timeFrame: Over 96 hours postdose
measure: Apparent terminal elimination half life (T1/2)
timeFrame: Over 96 hours postdose
measure: Apparent terminal elimination rate constant (λz).
timeFrame: Over 96 hours postdose
Secondary outcomes:
measure: Percentage of participants with Adverse Events (AEs)
timeFrame: From Baseline to Day 10
measure: Percentage of Participants with clinically significant changes from baseline in Laboratory Parameters
timeFrame: At Day 2, Day 5 and Day 10
measure: Percentage of participants with clinically significant change from baseline in physical examinations
timeFrame: At Day 1, 2 and 3, Day 5 and Day 10
measure: Percentage of Participants With Clinically Significant Changes from baseline in Vital Signs
timeFrame: At Day 1, 2 and 3, Day 5 and Day 10
measure: Percentage of participants with clinically significant change from baseline in 12-lead Electrocardiogram (ECG) readings
timeFrame: At Day 1, 2 and 3, Day 5 and Day 10
Other outcomes:
Locations:
city: Miami
country: United States
facility: ERG - Clinical Pharmacology of Miami
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: San Antonio
country: United States
facility: American Research Corporation/Texas Liver Institute
state: Texas
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References: