An Open-Label Study Following Oral Dosing of Seladelpar to Participants With Primary Biliary Cholangitis (PBC) and Hepatic Impairment (HI)
Purpose
The Effect of Hepatic Impairment on The Pharmacokinetics of Seladelpar: An Open-Label Study Following Oral Dosing of Seladelpar to Participants with Primary Biliary Cholangitis (PBC) and Hepatic Impairment (HI)
Conditions
- Primary Biliary Cholangitis
- Compensated Cirrhosis
- Hepatic Impairment
Eligibility
- Eligible Ages
- Between 18 Years and 80 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Males and females between 18 and 80 years of age (inclusive) who are able to comprehend instructions and follow the study procedures and are willing to sign an Informed Consent Form (ICF) 2. Females of childbearing potential who are sexually active with a non-sterile male partner (sterile male partners are defined as men vasectomized since at least 6 months) must be willing to use the contraceptive methods throughout the study and for 30 days after study drug administration. 3. For at least 90 days after study drug administration, non-vasectomized males must not donate sperm, be willing to use contraception with childbearing potential partners and any male participant with a pregnant partner must use a condom. 4. Willing to abstain from consuming grapefruit, pomelo, star fruit, or Seville orange containing products from 7 days prior to dose of study medication through day of discharge. 5. Confirmed diagnosis of PBC with evidence of cirrhosis and Child-Pugh classification of CP-A, CP-A + PHT, CP-B or CP-C 6. Screening laboratory parameters: - Alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 10 × upper Limit of normal (ULN) - Total bilirubin ≤ 5 × ULN 7. Ursodeoxycholic acid (UDCA) for a minimum of 12 weeks of treatment prior to Day 1 8. At screening confirmed diagnosis of PBC 9. Model for end-stage liver disease (MELD)-Na scores of 6 to 24
Exclusion Criteria
- Clinically significant or history of acute or chronic liver disease of an etiology other than PBC 2. Patients with a diagnosis of overlapping PBC and autoimmune hepatitis 3. History, evidence, or high suspicion of hepatobiliary malignancy based on imaging, screening laboratory values, and/or clinical symptoms. 4. Presumptive or diagnosed infection that requires systemic therapy within 12 weeks of Screening and through Day 1 5. Female participants who are pregnant or nursing 6. Screening electrocardiogram (ECG) that demonstrates a QT interval ≥ 500 msec, or any other significant ECG finding with clinically significant abnormalities as determined by the Investigator 7. Positive for hepatitis B surface antigen (HBsAg), hepatitis C virus - ribonucleic acid (HCV RNA), or anti human immunodeficiency virus (HIV) antibody 8. Any non-hepatic acute or chronic condition that, in the opinion of the Investigator, would limit the patient's ability to complete and/or participate in the study or compromise the integrity of the data 9. Has experienced an illness that is considered by the Investigator to be clinically significant within 2 weeks before administration of investigational product 10. Clinically relevant drug or alcohol abuse within 6 months of Screening. A positive drug screen will exclude participants unless it can be explained by a prescribed medication 11. Use of obeticholic acid (OCA), any drug of the same class, or fibrates (e.g., bezafibrate, fenofibrate, elafibranor, lanifibranor, pemafibrate, saroglitizar) within 30 days of Baseline 12. Use of an experimental or unapproved treatment for PBC within 30 days of Baseline 13. Clinically evident complication(s) of cirrhosis and portal hypertension that required either emergency room visit, hospital admission or both during the 12 week period prior to investigational product administration Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Part A: Cohort 1 - CP-A Without PHT (Seladelpar 10 mg) |
Participants with primary biliary cholangitis (PBC) and a Child-Pugh (CP) classification of CP-A (score 5 to 6) without portal hypertension (PHT) will receive a single dose of seladelpar 10 mg, orally, on Day 1. |
|
|
Experimental Part A: Cohort 2 - CP-A With PHT (Seladelpar 10 mg) |
Participants with PBC and a CP classification of CP-A (score 5 to 6) with PHT will receive a single dose of seladelpar 10 mg, orally, on Day 1. |
|
|
Experimental Part A: Cohort 3 - CP-B (Seladelpar 10 mg) |
Participants with PBC and a CP classification of CP-B (score 7 to 9) will receive a single dose of seladelpar 10 mg, orally, on Day 1. |
|
|
Experimental Part A: Cohort 4 - CP-C (Seladelpar 10 mg) |
Participants with PBC and a CP classification of CP-C (score 10 to 12) will receive a single dose of seladelpar 10 mg, orally, on Day 1. |
|
|
Experimental Experimental: Part B: Cohort 2 - CP-A With PHT (Seladelpar 5 mg or 10 mg) |
Participants with PBC and a CP classification of CP-A (score 5 to 6) with PHT, who complete Part A, will receive seladelpar 10 mg or 5 mg, orally, once daily, for 28 days. Doses for Part B will be chosen based on exposure from a single dose in Part A for individual participants. |
|
|
Experimental Experimental: Part B: Cohort 3 - CP-B (Seladelpar 5 mg or 10 mg) |
Participants with PBC and a CP classification of CP-B (score 7 to 9), who complete Part A, will receive seladelpar 10 mg or 5 mg, orally, once daily, for 28 days. Doses for Part B will be chosen based on exposure from a single dose in Part A for individual participants. |
|
More Details
- Status
- Completed
- Sponsor
- Gilead Sciences