Ensayos clínicos

Inclusion Criteria:

• Definite or probable primary biliary cirrhosis diagnosis (consistent with American Association for the Study of Liver Diseases [AASLD] and the European Association for the Study of the Liver [EASL] practice guidelines) as demonstrated by the presence of ≥2 of the following 3 diagnostic factors  
  • History of elevated Alkaline phosphatase levels for at least 6 months prior to day 0
  • Positive antimitochondrial antibody (AMA) titer or if AMA negative or in 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
• A mean total bilirubin >ULN and ≤3x ULN or an ALP >5x ULN
• Age ≥18 years
• Taking Ursodeoxycholic acid (UDCA) for at least 12 months (stable dose for ≥3 months) prior to day 0, or unable to tolerate UDCA (no UDCA for ≥3 months) prior to day 0
• Female subjects must be postmenopausal, surgically sterile, or if premenopausal, be prepared to use ≥1 effective (≤1% failure rate) method of contraception during the trial and for 30 days after the end of treatment visit. Effective methods of contraception are considered to be
  • Hormonal (e.g. contraceptive pill, patch, intramuscular implant or injection; or
  • Double barrier method, i.e. 
    • condom (male or female) 
    • diaphragm, with spermicide
  • Vasectomy (partner)
• Must provide written informed consent and agree to comply with the study protocol

Exclusion Criteria

• History or presence of other concomitant liver diseases including
  • Hepatitis B or C virus infection
  • Primary sclerosing cholangitis
  • Alcoholic liver disease
  • Definite autoimmune liver disease or overlap hepatitis
  • Nonalcoholic steatohepatitis
  • Gilbert's Syndrome
• Presence of clinical complications of PBC or clinically significant hepatic decompensation, including
  • History of liver transplant, current placement on a liver transplant list, or current Model of End Stage Liver Disease (MELD) score >12
  • Cirrhosis with complications, including history (within the past 12 months) or presence of
    • Variceal bleed
    • Uncontrolled ascites
    • Encephalopathy
    • Spontaneous bacterial peritonitis
  • Known or suspected hepatocellular carcinoma
  • Prior transjugular intrahepatic portosystemic shunt procedure
  • Hepatorenal syndrome (type I or II) or screening serum creatinine >2 mg/dL (178 μmol/L)
• Have undergone gastric bypass procedures (gastric lap band is acceptable) or ileal resection or plan to undergo either of these procedures
• Other medical conditions that may diminish life expectancy to <2 years, including known cancers (except carcinomas in situ or other stable, relatively benign conditions such as chronic lymphatic leukemia)
• History or presence of clinically concerning cardiac arrhythmias likely to affect survival during the study, or prolongation of screening (pretreatment) QT
• If female: plans to become pregnant, known pregnancy or a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating
• Known history of human immunodeficiency virus infection
• Medical conditions that may cause nonhepatic increases in ALP (eg, Paget's disease or fractures within 3 months)
• Other clinically significant medical conditions that are not well controlled or for which medication needs are anticipated to change during the study
• History of alcohol abuse or other substance abuse within 1 year prior to day 0
• Participation in another investigational product, biologic, or medical device study within 30 days prior to screening
  • Participation in a previous study of OCA is allowed with 3 months washout prior to enrollment in this study
• Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain
• History of known or suspected clinically significant hypersensitivity to OCA or any of its components