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

NCT04950764 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: CB8025-218382020-005925-10
• Study Type: interventional
• Target: 24
• Locations: 4 countries
• Sites: 20

Brief Summary

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

Keywords

PBC; Primary Biliary Cholangitis (PBC)

Outcome Measures

Primary Outcomes (18)

• Part A: Pharmacokinetic (PK) Parameter: Cmax of Seladelpar and Its Metabolites (M1, M2, and M3)

  Cmax is defined as the maximum observed plasma concentration of the study drug.

  Day 1: Predose; 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 hours postdose

• Part A: PK Parameter: Tmax of Seladelpar and Its Metabolites (M1, M2, and M3)

  Tmax is defined as the time to reach the maximum observed plasma concentration of the study drug.

  Day 1: Predose; 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 hours postdose

• Part A: PK Parameter: AUC0-t of Seladelpar and Its Metabolites (M1, M2, and M3)

  AUC0-t is defined as area under the concentration--time curve from time zero to the last measurable concentration.

  Day 1: Predose; 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 hours postdose

• Part A: PK Parameter: AUC0-inf of Seladelpar and Its Metabolites (M1, M2, and M3)

  AUC0-inf is defined as area under the concentration--time curve from time zero extrapolated to infinity, calculated as AUC0-t+Ct/Kel, where: Ct = the last measurable concentration and Kel = elimination rate constant.

  Day 1: Predose; 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 hours postdose

• Part B: PK Parameter: Cmax of Seladelpar and Its Metabolites (M1, M2, and M3)

  Cmax is defined as the maximum observed plasma concentration of the study drug.

  Day 1: Predose; 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, and 24 hours postdose

• Part B: PK Parameter: Cmax,ss of Seladelpar and Its Metabolites (M1, M2, and M3)

  Cmax,ss is defined as the steady-state maximum observed plasma concentration of the study drug at Day 28.

  Day 28: Predose; 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48, and 72 hours postdose

• Part B: PK Parameter: Tmax of Seladelpar and Its Metabolites (M1, M2, and M3)

  Tmax is defined as the time to reach the maximum observed plasma concentration of the study drug.

  Day 1: Predose; 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, and 24 hours postdose

• Part B: PK Parameter: Tmax,ss of Seladelpar and Its Metabolites (M1, M2, and M3)

  Tmax,ss is defined as the steady-state time to reach maximum observed plasma concentration of the study drug at Day 28.

  Day 28: Predose; 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48, and 72 hours postdose

• Part B: PK Parameter: AUC0-24 of Seladelpar and Its Metabolites (M1, M2, and M3)

  AUC0-24 is defined as area under the concentration-time curve from time zero to 24 hours.

  Day 1: Predose; 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, and 24 hours postdose

• Part B: PK Parameter: AUC0-tau of Seladelpar and Its Metabolites (M1, M2, and M3)

  AUCtau is defined as the area under the drug concentration versus time curve over the dosing interval.

  Day 28: Predose; 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48, and 72 hours postdose

• Part B: PK Parameter: RCmax of Seladelpar and Its Metabolites (M1, M2, and M3)

  RCmax is defined as the accumulation ratio based on Cmax, calculated as Cmax on Day 28/ Day 1.

  Day 28: Predose; 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48, and 72 hours postdose

• Part B: PK Parameter: RAUC0-t of Seladelpar and Its Metabolites (M1, M2, and M3)

  RAUC0-t is defined as the accumulation ratio based on AUC0-t, calculated as AUC0-tau on Day 28/ AUC0-24 on Day 1 for participants with dose once a day.

  Day 28: Predose; 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48, and 72 hours postdose

• Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) and Study Drug-Related TEAEs

  An adverse event (AE) was defined as any medical occurrence in a participant administered to a pharmaceutical product in a clinical study, regardless of a causal relationship with this treatment. TEAEs were defined as AEs that commenced or worsened on or after the time of study drug administration in Part A until up to 30 days after study drug administration in Part A or before the first study drug administration in Part B (whichever is earlier). For Part B, TEAEs are defined as AEs that commence or worsen on or after the time of first study drug administration in Part B until up to 30 days after the last study drug administration in Part B. A drug-related TEAE was defined as TEAE which was related (reported as 'possible', 'probable', or 'definite') to study drug. Percentages were rounded off.

  Part A: Up to Week 5; Part B: Up to Week 8

• Percentage of Participants Who Experienced Any Grade and Grade 3 or 4 TEAEs

  TEAEs severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Fatal. Participants were counted at the highest AE grade experienced. The percentage of participants with any severity grade and severity grade of 3 or 4 were reported. Percentages were rounded off.

  Part A: Up to Week 5; Part B: Up to Week 8

• Percentage of Participants Who Experienced TEAEs of Special Interest

  TEAEs of special interest for this study were defined as AEs that met CTCAE version 5.0 or the most recent version Grade 2 criteria or higher for AEs of elevated alanine transaminase (ALT), aspartate aminotransferase (AST), bilirubin, creatinine kinase, lipase, or serum creatinine. Hepatic decompensation clinical events including ascites, jaundice, esophageal variceal bleeding, and hepatic encephalopathy, were also defined as TEAEs of special interest for this study. Percentages were rounded off.

  Part A: Up to Week 5; Part B: Up to Week 8

• Percentage of Participants With Clinically Significant Changes in Vital Signs

  Vital signs (including oral temperature, respiratory rate, seated blood pressure \[diastolic and systolic\], and heart rate) were evaluated. Percentage of participants with clinically significant changes in vital signs evaluations was reported. The clinically significant changes were based on investigator's judgement.

  Part A: Up to Day 4; Part B: Up to Day 31

• Percentage of Participants With Abnormal Clinically Significant 12-Lead Electrocardiogram (ECG) Findings

  ECG measurements included the parameters of heart rate, ventricular rate, PR interval, QRS duration, QT interval (uncorrected), and QT interval corrected for heart rate according to Fridericia's formula (QTcF). Per protocol, ECG findings were classified in 1 of 3 categories: normal, abnormal but not clinically significant, or abnormal and clinically significant. Any abnormality in ECG assessments which were deemed clinically significant by the investigator were reported.

  Part A: Up to Day 4; Part B: Up to Day 28

• Percentage of Participants Who Experienced Laboratory Abnormalities

  Clinical laboratory parameters included biochemistry, hematology, coagulation, and urinalysis. Abnormal laboratory values were graded according to the NCI CTCAE version 5.0.Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Fatal. The percentage of participants with a shift of ≥ 2 NCI CTCAE grade from baseline was reported.

  Part A: Up to Day 4; Part B: Up to Day 31

Secondary Outcomes (26)

• Part A: PK Parameter (Urine): Ae0-t of Seladelpar and Its Metabolites (M1, M2, and M3)

  Day 1: Predose; 0-6 h, and 6-12 h postdose

• Part A: PK Parameter (Urine): CLR of Seladelpar

  Day 1: Predose; 0-6 h, and 6-12 h postdose

• Part A: Rsq Between Plasma Seladelpar Cmax and Baseline Albumin

  Day 1: Predose; 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 hours postdose

• Part A: Rsq Between Plasma Seladelpar AUC0-inf and Baseline Albumin

  Day 1: Predose; 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 hours postdose

• Part A: Rsq Between Plasma Seladelpar AUC0-t and Baseline Albumin

  Day 1: Predose; 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 hours postdose

Study Arms (6)

Part A: Cohort 1 - CP-A Without PHT (Seladelpar 10 mg)

EXPERIMENTAL

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.

Drug: Seladelpar

Part A: Cohort 2 - CP-A With PHT (Seladelpar 10 mg)

EXPERIMENTAL

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.

Drug: Seladelpar

Part A: Cohort 3 - CP-B (Seladelpar 10 mg)

EXPERIMENTAL

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.

Drug: Seladelpar

Part A: Cohort 4 - CP-C (Seladelpar 10 mg)

EXPERIMENTAL

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.

Drug: Seladelpar

Experimental: Part B: Cohort 2 - CP-A With PHT (Seladelpar 5 mg or 10 mg)

EXPERIMENTAL

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.

Drug: Seladelpar

Experimental: Part B: Cohort 3 - CP-B (Seladelpar 5 mg or 10 mg)

EXPERIMENTAL

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.

Drug: Seladelpar

Interventions

Seladelpar DRUG

Tablets Administered Orally

Also known as: Livdelzi®

Experimental: Part B: Cohort 2 - CP-A With PHT (Seladelpar 5 mg or 10 mg); Experimental: Part B: Cohort 3 - CP-B (Seladelpar 5 mg or 10 mg); Part A: Cohort 1 - CP-A Without PHT (Seladelpar 10 mg); Part A: Cohort 2 - CP-A With PHT (Seladelpar 10 mg); Part A: Cohort 3 - CP-B (Seladelpar 10 mg); Part A: Cohort 4 - CP-C (Seladelpar 10 mg)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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.
• 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.
• 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.
• Confirmed diagnosis of PBC with evidence of cirrhosis and Child-Pugh classification of CP-A, CP-A + PHT, CP-B or CP-C
• Screening laboratory parameters:
• Alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 10 × upper Limit of normal (ULN)
• Total bilirubin ≤ 5 × ULN
• Ursodeoxycholic acid (UDCA) for a minimum of 12 weeks of treatment prior to Day 1
• At screening confirmed diagnosis of PBC
• Model for end-stage liver disease (MELD)-Na scores of 6 to 24

You may not qualify if:

• Clinically significant or history of acute or chronic liver disease of an etiology other than PBC
• Patients with a diagnosis of overlapping PBC and autoimmune hepatitis
• History, evidence, or high suspicion of hepatobiliary malignancy based on imaging, screening laboratory values, and/or clinical symptoms.
• Presumptive or diagnosed infection that requires systemic therapy within 12 weeks of Screening and through Day 1
• Female participants who are pregnant or nursing
• 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
• Positive for hepatitis B surface antigen (HBsAg), hepatitis C virus - ribonucleic acid (HCV RNA), or anti human immunodeficiency virus (HIV) antibody
• 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
• Has experienced an illness that is considered by the Investigator to be clinically significant within 2 weeks before administration of investigational product
• 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
• 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
• Use of an experimental or unapproved treatment for PBC within 30 days of Baseline
• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (20)

Arizona Liver Health

Chandler, Arizona, 85224, United States

Location

University of California Davis

Sacramento, California, 95817, United States

Location

University of Colorado Anschutz

Aurora, Colorado, 80045, United States

Location

Mercy Medical Center

Baltimore, Maryland, 21202, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Henry Ford Health System

Novi, Michigan, 48377, United States

Location

Southern Therapy and Advanced Research LLC

Jackson, Mississippi, 39216, United States

Location

Weill Medical College of Cornell University

New York, New York, 10021, United States

Location

The Liver Institute at Methodist Dallas Medical Center

Dallas, Texas, 75203, United States

Location

American Research Corporation

San Antonio, Texas, 78215, United States

Location

Pinnacle Clinical Research- SA

San Antonio, Texas, 78229, United States

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

Inje University Busan Paik Hospital

Busan, South Korea

Location

Kyungpook National University Hospital

Daegu, 41944, South Korea

Location

Seoul National University Hospital

Seoul, 3080, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, 3722, South Korea

Location

Hospital General Universitario Gregorio Maran

Madrid, 28007, Spain

Location

NIHR BRC Centre for Liver and Gastrointestinal Research Birmingham

Birmingham, B15 2GW, United Kingdom

Location

The Royal Free London NHS Foundation Trust

London, NW2 2QG, United Kingdom

Location

Kings College Hospital

London, SE5 9RS, United Kingdom

Location

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Interventions

seladelpar

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2021
• First Posted: July 6, 2021
• Study Start: November 16, 2021
• Primary Completion: February 24, 2025
• Study Completion: February 27, 2025
• Last Updated: May 4, 2026
• Results First Posted: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 18 months after study completion and at least 6 months after the FDA and EMA approval
• Access Criteria: A secured external environment with username, password, and RSA code.

Locations

US (11); KR (5); GB (3); ES (1)