study of obeticholic acid (oca) evaluating pharmacokinetics and safety in participants with primary biliary cholangitis (pbc) and hepatic impairment

Conditions: Liver Cirrhosis, Biliary

Summary: 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.


Eligibility criteria:
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.

Keywords: primary biliary cholangitis primary biliary cirrhosis pbc hepatic impairment cirrhosis liver