Clinical trial NCT04950764: An Open-Label Study Following Oral Dosing of Seladelpar to Subjects With Primary Biliary Cholangitis (PBC) and Hepatic Impairment (HI)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Primary Biliary Cholangitis
Compensated Cirrhosis
Hepatic Impairment
Keywords: PBC
Primary Biliary Cholangitis (PBC)
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2021-07-06
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Seladelpar 10 mg
Primary purpose: TREATMENT

Brief summary: 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)


Eligibility criteria: 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

Primary outcomes:
measure: Evaluate maximum concentration (Cmax) of seladelpar and metabolites
timeFrame: 17 weeks
measure: Evaluate the time to reach Cmax (Tmax) of seladelpar and metabolites
timeFrame: 17 weeks
measure: Evaluate area under the concentration curve versus time curve of seladelpar and metabolites
timeFrame: 17 weeks
measure: Evaluate the amount of seladelpar excreted in the urine (Ae)
timeFrame: 17 weeks
measure: Evaluate safety and tolerability as assessed by the incidence of treatment emergent adverse events and serious treatment emergent adverse events across child pugh treatment groups
timeFrame: 17 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Arizona Liver Health
state: Arizona
city: Sacramento
country: United States
facility: University of California Davis
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz
state: Colorado
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Novi
country: United States
facility: Henry Ford Health System
state: Michigan
city: Jackson
country: United States
facility: Southern Therapy and Advanced Research LLC
state: Mississippi
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: Dallas
country: United States
facility: The Liver Institute at Methodist Dallas Medical Center
state: Texas
city: San Antonio
country: United States
facility: American Research Corporation
state: Texas
city: San Antonio
country: United States
facility: Pinnacle Clinical Research- SA
state: Texas
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maran
city: Birmingham
country: United Kingdom
facility: NIHR BRC Centre for Liver and Gastrointestinal Research Birmingham
city: London
country: United Kingdom
facility: The Royal Free London NHS Foundation Trust
city: London
country: United Kingdom
facility: Kings College Hospital
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: