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

This is an interventional treatment trial for Liver Cirrhosis, Biliary focused on measuring Primary Biliary Cholangitis, Primary Biliary Cirrhosis, PBC, Hepatic Impairment, Cirrhosis, Liver Read More

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.