A Study of INT-747 (6-ECDCA) in Combination with Ursodeoxycholic Acid (URSO®, UDCA) in Patients with Primary Biliary Cirrhosis

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 30

Inclusion Criteria

•Male or female age 18 to 70 years.
•Stable dose of ursodeoxycholic acid (URSO®, UDCA) for at least 6 months prior to screening.
• Female patients must be postmenopausal, surgically sterile, or if premenopausal, prepared to use 1 effective method of contraception with all sexual partners during the study and for 14 days after the end of dosing. Effective methods of contraception are considered to be: o Barrier method, i.e., (a) condom (male or female) or (b) diaphragm with spermicide; or o Hormonal (e.g., contraceptive pill, patch); or o Intrauterine device (IUD); or o Vasectomy (partner).
• Male patients must be prepared to use 1 effective method of contraception with all sexual partners during the study unless they have had a prior vasectomy.
• Proven or likely PBC, as demonstrated by the patient presenting with at least 2 of the following 3 diagnostic factors:
o History of increased AP levels for at least 6 months prior to Day 0
o Positive AMA titer (>1:40 titer on immunofluorescence or M2 positive by ELISA) or PBC-specific antinuclear antibodies (antinuclear dot and nuclear rim positive)
o Liver biopsy consistent with PBC
• Screening AP level between 1.5 and 10 × ULN.
• Willing and able to give written informed consent

Exclusion Criteria

• Administration of the following drugs at any time during the 3 months prior to screening for the study: colchicine, methotrexate, azathioprine, or systemic corticosteroids.
• Screening conjugated (direct) bilirubin >2 × ULN.
• Screening ALT or AST >5 × ULN.
• Screening serum creatinine >1.5 mg/dL (133 micromol/L).
• History or presence of hepatic decompensation (e.g., variceal bleeds, encephalopathy, or poorly controlled ascites).
• History or presence of other concomitant liver diseases including hepatitis due to hepatitis B or C virus (HCV, HBV) infection, primary sclerosing cholangitis (PSC), alcoholic liver disease, definite autoimmune liver disease or biopsy proven nonalcoholic steatohepatitis (NASH).
• Known history of human immunodeficiency virus (HIV) infection.
• History or presence of any other disease or condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs including bile salt metabolism in the large intestine (e.g., inflammatory bowel disease).
• Other clinically significant medical conditions, including renal insufficiency.
• Other medical conditions that are not well controlled or for which medication needs are anticipated to change during the study. Concomitant medications must be stable for 14 days prior to the first dose of study medication, and should be expected to remain stable during the course of the study.
• History of alcohol abuse (defined as consumption of more than 210 mL of alcohol per week; or the equivalent of 14 4-ounce glasses of wine, or 14 12-ounce cans/bottles of beer or wine coolers) or other substance abuse within the prior 1 year.
• Participation in another investigational drug, biologic, or medical device study within 30 days prior to Day 0.
• History of noncompliance with medical regimens, or patients who are considered to be potentially unreliable.
• Blood or plasma donation within 30 days prior to dosing.
• Mental instability or incompetence, such that the validity of informed consent or compliance with the study is uncertain.
• If female: pregnant, lactating, or positive serum or urine pregnancy test.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary efficacy endpoint is the effect of INT-747 on serum AP levels at<br /><br>baseline (Day 0) and the end of the study (Day 85). </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Safety and secondary efficacy endpoints will be evaluated by monitoring the<br /><br>following:<br /><br>- Adverse experiences<br /><br>- Clinical laboratory values (including aminotransferase liver enzymes, protein<br /><br>concentrations, and prothrombin time to assess hepatocellular injury and liver<br /><br>function)<br /><br>- Vital signs<br /><br>- Disease-specific and general health questionnaires (PBC-40, 5D, and SF-36)<br /><br>- Symptoms (pruritus VAS questionnaire)<br /><br>- Liver inflammation and fibrosis biomarkers<br /><br>- Plasma drug and metabolite concentrations </p><br>

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