Understanding how liver impairment affects palovarotene levels in the blood

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

This study is testing how well the body processes a medication called palovarotene in people with moderate and severe liver problems compared to those with healthy livers.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 32 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Ipsen (Industry-sponsored)
• Locations: 3 sites (Miami, Florida and 2 other locations)
• Trial ID: NCT06908954 on ClinicalTrials.gov

What this trial studies

This study aims to investigate how moderate and severe liver impairment influences the body's processing of a single dose of palovarotene, a medication, compared to healthy individuals with normal liver function. Participants will be divided into three groups based on their liver function: healthy participants, those with moderate impairment, and those with severe impairment, with the latter group only being enrolled if safety is confirmed from the moderate group. Blood samples will be collected to analyze drug binding to proteins, and participants will undergo safety assessments over a five-day period, returning for a final visit on Day 10.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 to 70 with chronic hepatic disease and varying degrees of liver function impairment.

Not a fit: Patients with acute liver disease or those not meeting the specific inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide critical insights into the safe use of palovarotene in patients with liver impairment.

How similar studies have performed: While there may be studies on drug metabolism in liver impairment, this specific approach to palovarotene is novel and not extensively tested.

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.

Where this trial is running

Miami, Florida and 2 other locations

• ERG - Clinical Pharmacology of Miami — Miami, Florida, United States (Recruiting)
• Orlando Clinical Research Center — Orlando, Florida, United States (Recruiting)
• American Research Corporation/Texas Liver Institute — San Antonio, Texas, United States (Recruiting)

Study contacts

• Study coordinator: Ipsen Clinical Study Enquiries

Conditions Hepatic Impairment; Healthy