Primary Biliary Cholangitis and Moderate to Severe Hepatic Impairment
Conditions
Sponsors
Intercept Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion 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 [Lindor 2009, EASL 2009]), defined as having =2 of the following 3 diagnostic factors: - History of elevated 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-GP210 and/or anti-SP100) and/or antibodies against the major M2 components (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 TE Value =16.9 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 (=65 years) yes F.1.3.1 Number of subjects for this age range 19
Exclusion criteria
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. Current 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 RNA positive • Active hepatitis B infection; however, patients 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the PK of OCA and its conjugates, glyco-OCA and tauro-OCA, and OCA metabolite glucuronide compared with placebo. To evaluate the safety and tolerability of OCA treatment compared with placebo;Secondary Objective: To evaluate the effect of OCA treatment compared to placebo on: - The MELD score and its components - CP score and its components - Liver biochemistry including total and direct bilirubin, alkaline phosphatase (ALP), and aminotransferases (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and gamma glutamyl transaminase [GGT]), international normalized ratio (INR), creatinine, albumin, platelets - Biomarkers of bile acid synthesis and homeostasis including fibroblast growth factor 19 (FGF-19), 7a-hydroxy-4-cholesten-3-one (C4), and plasma bile acids;Primary end point(s): Primary Objective: • To evaluate the pharmacokinetics (PK) of OCA and its conjugates, glyco-OCA and tauro-OCA, and metabolite OCA glucuronide compared with placebo • To evaluate the safety and tolerability of OCA treatment compared with placebo;Timepoint(s) of evaluation of this end point: week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • To evaluate the effect of OCA treatment compared to placebo on: - The model of end stage liver disease (MELD) score and its components - Child-Pugh (CP) score and its components - Liver biochemistry including total and direct bilirubin, alkaline phosphatase (ALP), and aminotransferases (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and gamma glutamyl transaminase [GGT]), international normalized ratio (INR), creatinine, albumin, platelets - Biomarkers of bile acid synthesis and homeostasis including fibroblast growth factor 19 (FGF-19), 7a-hydroxy-4-cholesten-3-one (C4), and plasma bile acids ;Timepoint(s) of evaluation of this end point: week 48 | — |
Countries
Argentina, Australia, Belgium, Brazil, Estonia, Germany, Hungary, Italy, Lithuania, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactSusanna Giorgi
INC Research, LLC
Outcome results
None listed