Obeticholic Acid (OCA) in Primary Sclerosing Cholangitis (PSC)

Inclusion Criteria

• Must have had a diagnosis of PSC (based on cholangiography at any point in time).
• Alkaline phosphatase at Screening ≥2x ULN.
• Total bilirubin at Screening 4x ULN at Screening or evidence of IgG4 sclerosing cholangitis.
• Small duct cholangitis in the absence of large duct disease.
• Presence of clinical complications of chronic liver disease or clinically significant hepatic decompensation, including:
• Current Child Pugh classification B or C
• History of, or current diagnosis or suspicion of, cholangiocarcinoma or other hepatobiliary malignancy, or biliary tract dysplasia.
• History of liver transplantation, or current model of end stage liver disease score ≥12
• History of, or current, cirrhosis with complications, including history or presence of spontaneous bacterial peritonitis hepatocellular carcinoma or hepatic encephalopathy (as assessed by the Investigator)
• Current known portal hypertension with complications, including known gastric or large esophageal varices, poorly controlled or diuretic resistant ascites, history of variceal bleeds, or related therapeutic or prophylactic interventions (for example, beta blockers, insertion of variceal bands or transjugular intrahepatic portosystemic shunt).
• History of, or current, hepatorenal syndrome (type I or II) or Screening serum creatinine >2 mg/deciliter (178 micromoles/liter [L]).
• Platelet count ULN or unconjugated (indirect) bilirubin >ULN at Screening.
• Known history of human immunodeficiency virus infection.
• Currently experiencing, or experienced within ≤3 months of Screening, pruritus requiring systemic or enteral treatment.
• Known or suspected acute cholangitis in the 3 months prior to, and including, Day 0 including cholangitis treated with antibiotics.
• Administration of antibiotics is prohibited ≤1 month of Day 0 (unless participant was on a stable prophylaxis dose for at least 3 months prior to Day 0).
• Administration of the following medications was prohibited ≤6 months of Day 0 and throughout the trial: fenofibrate or other fibrates and potentially hepatotoxic medications (including alpha-methyl-dopa, sodium valproic acid, isoniazide, or nitrofurantoin).
• IBD flare during Screening (up to and including Day 0), where "flare" was defined as follows:
• UC flare: partial Mayo Score ≥5, and
• CD flare: CDAI ≥250
• Evidence of deleterious effects of alcohol abuse (as assessed by the Investigator) or excessive alcohol consumption (>4 units/day for males, >2 units/day for females).
• Known or suspected use of illicit drugs or drugs of abuse (allowed if medically prescribed or indicated) within 3 months of Day 0.
• If female: known pregnancy, or had a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating.
• Other concomitant disease, malignancy, or condition likely to significantly decrease life expectancy to less than the duration of the trial (for example, moderate to severe congestive heart failure).
• Participation in another investigational drug, biologic, or medical device trial within 30 days prior to Screening.
• History of noncompliance with medical regimens, or participants who were considered to be potentially unreliable.
• Blood or plasma donation within 30 days prior to Day 0.
• Mental instability or incompetence such that the validity of informed consent or compliance with the trial was uncertain.