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

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-001425-10-NL
• Date of registration: 03/09/2008
• Prospective Registration: Yes
• Primary sponsor: Intercept Pharmaceuticals
• Public title: A Study of INT-747 (6-ECDCA) in Combination with Ursodeoxycholic Acid (URSO®, UDCA) in Patients with Primary Biliary Cirrhosis
• Scientific title: A Study of INT-747 (6-ECDCA) in Combination with Ursodeoxycholic Acid (URSO®, UDCA) in Patients with Primary Biliary Cirrhosis
• Date of first enrolment: 11/02/2009
• Target sample size: 140
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-001425-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Austria, France, Germany, Netherlands, Spain, United Kingdom

Key inclusion & exclusion criteria

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.
•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
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:
• 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 ?mol/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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Primary biliary cirrhosis
MedDRA version: 9.1 Level: PT Classification code 10004661 Term: Biliary cirrhosis primary

Intervention(s)

Product Name: INT-747
Product Code: INT-747
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: 3a,7a-dihydroxy-6a-ethyl-5ßcholan-24-oic acid
CAS Number: 459789-99-2
Current Sponsor code: 6-ECDCA or INT-747
Other descriptive name: 6a-ethylchenodeoxycholic acid, 6-ethylchenodeoxycholic acid
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: INT-747
Product Code: INT-747
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: 3a,7a-dihydroxy-6a-ethyl-5ßcholan-24-oic acid
CAS Number: 459789-99-2
Current Sponsor code: 6-ECDCA or INT-747
Other descriptive name: 6a-ethylchenodeoxycholic acid , 6-ethylchenodeoxycholic acid
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: INT-747
Product Code: INT-747
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: 3a,7a-dihydroxy-6a-ethyl-5ßcholan-24-oic acid
CAS Number: 459789-99-2
Current Sponsor code: 6-ECDCA or INT-747
Other descriptive name: 6a-ethylchenodeoxycholic acid , 6-ethylchenodeoxycholic acid
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary objectives of this study are to assess the effects of INT-747 in patients with proven or likely PBC in combination with ursodeoxycholic acid (URSO®, UDCA), on:
• Alkaline Phosphatase levels
• Safety

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.

Secondary Objective: The secondary objectives of this study are to assess the effects of INT-747 in patients with proven or likely PBC in combination with ursodeoxycholic acid (URSO®, UDCA), on:
•Hepatocellular injury and liver function
•Disease-specific and general health symptoms
•Biomarkers of hepatic inflammation and fibrosis
•Plasma trough concentrations of INT-747 and its major, known metabolites

Secondary ID(s)

747-202

2007-001425-10-GB