An Open-Label Study Following Oral Dosing of Seladelpar to Subjects With Primary Biliary Cholangitis (PBC) and Hepatic Impairment (HI)

Gilead Sciences

Status and phase: Completed; Phase 1

Conditions: Hepatic Impairment; Compensated Cirrhosis; Primary Biliary Cholangitis

Treatments: Drug: Seladelpar 10 mg or less; Drug: Seladelpar 10 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT04950764

CB8025-21838

2020-005925-10 (Other Identifier)

Details and patient eligibility

About

The Effect of Hepatic Impairment on The Pharmacokinetics of Seladelpar: An Open-Label Study Following Oral Dosing of Seladelpar to Subjects with Primary Biliary Cholangitis (PBC) and Hepatic Impairment (HI)

Enrollment: 24 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. 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 subject 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:

   • ALP, ALT and AST < 10 × 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. MELD-Na scores of 6 to 24

Exclusion criteria

1. 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 subjects who are pregnant or nursing
6. Screening 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 HBsAg, HCV RNA, or anti 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 subjects 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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24 participants in 2 patient groups

Seladelpar 10 mg

Experimental group

Description:

Part A: Single oral dose 10 mg

Treatment:

Drug: Seladelpar 10 mg

Seladelpar 10 mg or less

Experimental group

Description:

Part B: Multiple oral dose of 10 mg or less

Treatment:

Drug: Seladelpar 10 mg or less