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

Hepatic Impairment Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04950764
• Other study ID #: CB8025-21838
• Status: Recruiting
• Phase: Phase 1
• Start date: September 17, 2021
• Est. completion date: June 2024

Study information

• Verified date: April 2023
• Source: CymaBay Therapeutics, Inc.
• Contact: Barry Crittenden, MD
• Phone: 510-293-8800
• Email: medinfo[@]cymabay.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: June 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Cholangitis
• Compensated Cirrhosis
• Hepatic Impairment
• Liver Cirrhosis, Biliary
• Liver Diseases
• Primary Biliary Cholangitis

Intervention

Drug:
• Seladelpar 10 mg
Seladelpar 10 mg single oral dose
• Seladelpar 10 mg or less
Seladelpar 10 mg or less, once daily for 28 days

Locations

Country	Name	City	State
Korea, Republic of	Inje University Busan Paik Hospital	Busan
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Korea - Kyungpook National University Hospital	Daegu
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Spain	Hospital General Universitario Gregorio Marañón	Madrid
United Kingdom	University Hopsitals Birmingham	Birmingham
United Kingdom	King's College NHS Foundation Trust	London
United Kingdom	The Royal Free London NHS Foundation Trust	London
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado
United States	Mercy Medical Center	Baltimore	Maryland
United States	The Institute of Liver Health dba Arizona Liver Health	Chandler	Arizona
United States	The Liver Institute at Methodist Dallas Medical Center	Dallas	Texas
United States	Southern Therapy and Advanced Research	Jackson	Missouri
United States	Henry Ford Columbus Center	Novi	Michigan
United States	University of California Davis Medical Center	Sacramento	California
United States	American Research Corporation at the Texas Liver Institute	San Antonio	Texas
United States	Pinnacle Clinical Research	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
CymaBay Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Korea, Republic of,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate maximum concentration (Cmax) of seladelpar and metabolites		17 weeks
Primary	Evaluate the time to reach Cmax (Tmax) of seladelpar and metabolites		17 weeks
Primary	Evaluate area under the concentration curve versus time curve of seladelpar and metabolites		17 weeks
Primary	Evaluate the amount of seladelpar excreted in the urine (Ae)		17 weeks
Primary	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		17 weeks