A Study of INT-747 (6-ECDCA) Monotherapy in Patientswith Primary Biliary Cirrhosis

Phase 1

• Conditions: Primary biliary cirrhosis; MedDRA version: 9.1Level: PTClassification code 10004661Term: Biliary cirrhosis primary

• Registration Number: EUCTR2007-001424-12-FR
• Lead Sponsor: Intercept Pharmaceuticals

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-05-16
• Last Update Posted: 8 January 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

Patients are required to meet the following criteria in order to be included in the study:
•Male or female age 18 to 70 years.
•Female patients must be postmenopausal or surgically sterile.
•Male patients must be prepared to use 2 methods of contraception with all sexual partners during the study and for 90 days after the end of dosing, 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:
oHistory of increased AP levels for at least 6 months prior to Day 0
oPositive AMA titer (>1:40 titer on immunofluorescence or M2 positive by ELISA) or PBC-specific antinuclear antibodies (antinuclear dot and nuclear rim positive)
oLiver biopsy consistent with PBC
•Screening AP level between 1.5 and 10 × ULN
•Willing and able to give written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Patients with the following characteristics will be excluded from the study:
•Females of child bearing potential
•Administration of the following drugs at any time during the 3 months prior to screening for the study: ursodeoxycholic acid (UDCA, Urso®), colchicine, methotrexate, azathioprine, or systemic corticosteroids
•Screening conjugated (direct) bilirubin >2 × ULN
•Screening ALT or AST >5 × ULN
•Screening serum creatinine >133 umol/L (>1.5 mg/dL)
•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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objectives of this study are to assess the effects of INT-747 in patients with proven or likely PBC on:<br>• Alkaline Phosphatase levels<br>• Safety<br>;Secondary Objective: The secondary objectives of this study are to assess the effects of INT-747 in patients with proven or likely PBC on:<br>•Hepatocellular injury and liver function <br>•Disease-specific and general health symptoms<br>•Biomarkers of hepatic inflammation and fibrosis<br>•Plasma trough concentrations of INT-747 and its major, known metabolites<br>;Primary end point(s): The primary efficacy endpoint for this study is the effect of INT-747 on serum AP levels. The specific statistical analyses regarding serum AP levels will be specified in the statistical analysis plan.