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

Sponsor

CymaBay Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04950764

Collaborator

(none)

Enrollment

Locations

Arms

17.4

Anticipated Duration (Months)

2.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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)

Condition or Disease	Intervention/Treatment	Phase
Primary Biliary Cholangitis Compensated Cirrhosis Hepatic Impairment	Drug: Seladelpar 10 mg Drug: Seladelpar 10 mg or less	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Intervention Model Description:

Seladelpar 10 mgSeladelpar 10 mg

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 17, 2021

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Mar 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Seladelpar 10 mg Part A: Single oral dose 10 mg	Drug: Seladelpar 10 mg Seladelpar 10 mg single oral dose
Experimental: Seladelpar 10 mg or less Part B: Multiple oral dose of 10 mg or less	Drug: Seladelpar 10 mg or less Seladelpar 10 mg or less, once daily for 28 days

Arm

Intervention/Treatment

Experimental: Seladelpar 10 mg

Part A: Single oral dose 10 mg

Drug: Seladelpar 10 mg

Seladelpar 10 mg single oral dose

Experimental: Seladelpar 10 mg or less

Part B: Multiple oral dose of 10 mg or less

Drug: Seladelpar 10 mg or less

Seladelpar 10 mg or less, once daily for 28 days

Outcome Measures

Primary Outcome Measures

Evaluate maximum concentration (Cmax) of seladelpar and metabolites [17 weeks]
Evaluate the time take to reach Cmax (Tmax) of seladelpar and metabolites [17 weeks]
Evaluate area under the concentration curve versus time curve of seladelpar and metabolites [17 weeks]
Evaluate the amount of seladelpar excreted in the urine (Ae) [17 weeks]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)
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 subject 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:

ALP, ALT and AST < 10 × 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
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
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 subjects who are pregnant or nursing
Screening 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 HBsAg, HCV RNA, or anti 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 subjects 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California Davis Medical Center	Sacramento	California	United States	95817
2	University of Colorado Anschutz Medical Campus	Aurora	Colorado	United States	80045
3	Mercy Medical Center	Baltimore	Maryland	United States	21202
4	Henry Ford Columbus Center	Novi	Michigan	United States	48377
5	Southern Therapy and Advanced Research	Jackson	Missouri	United States	39216
6	The Liver Institute at Methodist Dallas Medical Center	Dallas	Texas	United States	75203
7	American Research Corporation at the Texas Liver Institute	San Antonio	Texas	United States	78215
8	Pinnacle Clinical Research	San Antonio	Texas	United States	78229
9	Pusan National University Hospital	Busan		Korea, Republic of	49241
10	Seoul National University Hospital	Seoul		Korea, Republic of	03080
11	Hospital General Universitario Gregorio Marañón	Madrid		Spain	28007