Study of Obeticholic Acid (OCA) Evaluating Pharmacokinetics and Safety in Participants With Primary Biliary Cholangitis (PBC) and Hepatic Impairment

A Phase 4, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Pharmacokinetics and Safety of Obeticholic Acid in Patients With Primary Biliary Cholangitis and Moderate to Severe Hepatic Impairment

This Phase 4, randomized, double-blind, placebo-controlled study will evaluate the pharmacokinetics (PK) and safety of OCA treatment in participants with PBC and moderate to severe hepatic impairment over a 48-week treatment period. Participants who have completed their 48-week double blind treatment period will continue double-blind treatment until all randomized participants have completed their 48-week treatment period and the database for that period is locked. An open-label extension study in which all participants receive OCA will be considered following review of blinded safety and PK data.

Inclusion Criteria:

1. A definite or probable diagnosis of PBC (consistent with American Association for the Study of Liver Diseases [AASLD] and European Association for the Study of the Liver [EASL] Practice Guidelines, defined as having ≥2 of the following 3 diagnostic factors:

   • History of elevated alkaline phosphatase (ALP) levels for at least 6 months
   • Positive antimitochondrial antibody (AMA) titer or if AMA negative or low titer (≤1:80), PBC specific antibodies (anti-glycoprotein 210 [GP210] and/or anti-SP100) and/or antibodies against the major M2 components (E2 component of mitochondrial pyruvate dehydrogenase complex [PDC-E2], 2-oxo-glutaric acid dehydrogenase complex)
   • Liver biopsy consistent with PBC (collected at any time prior to Screening)

2. Evidence of cirrhosis including at least one of the following:

   • Biopsy results consistent with PBC Stage 4

   • Liver stiffness as assessed by Transient Elastography (TE) Median Value ≥16.9 kilopascals (kPa)

   • Clinical evidence in the absence of acute liver failure consistent with cirrhosis including: gastroesophageal varices, ascites, radiological evidence of cirrhosis (nodular liver or enlargement of portal vein and splenomegaly)

   • Combined low platelet count (<140,000/cubic millimeter [mm^3]) with

     • persistent decrease in serum albumin, or
     • elevation in prothrombin time/international normalized ratio (INR) (not due to antithrombotic agent use), or
     • elevated bilirubin (2*upper limit of normal [ULN])

3. Satisfy the criteria of the modified Child-Pugh (CP) classification for hepatic impairment during Screening:

   • Moderate: CP-B (Scores 7 to 9) or
   • Severe: CP-C (Scores 10 to 12)

4. Model of end-stage liver disease (MELD) score of 6 to 24 at Screening

5. Taking ursodeoxycholic acid (UDCA) for at least 12 months (stable dose for ≥3 months) prior to Day 1, or unable to tolerate or unresponsive to UDCA (no UDCA for ≥3 months)

Exclusion Criteria:

1. Non-cirrhotic or cirrhotic CP-A (Mild; Score 5 to 6)

2. History of liver transplant or organ transplant

3. History of alcohol or drug abuse within 12 months prior to Screening

4. Hepatic encephalopathy (as defined by a West Haven score of ≥2

5. History or presence of other concomitant liver diseases including:

   • Hepatitis C virus infection and ribonucleic acid (RNA) positive
   • Active hepatitis B infection; however, participants who have seroconverted (hepatitis B surface antigen and hepatitis B e antigen negative) may be included in this study after consultation with the medical monitor
   • Primary sclerosing cholangitis
   • Alcoholic liver disease
   • Definite autoimmune liver disease or overlap hepatitis
   • Gilbert's Syndrome

6. In the opinion of the Investigator, fluctuating or rapidly deteriorating hepatic function prior to randomization

Other inclusion/exclusion criteria may apply.