Contact information
Type
Scientific
Primary contact
Dr Erin Castelloe
ORCID ID
Contact details
Clinical Consultant - Pharmacovigilance
4370 La Jolla Village Drive
Suite 1050
San Diego
92122
United States of America
+1 (0)858 354 6441
ecastelloe@interceptpharma.com
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT00550862
Protocol/serial number
747-202
Study information
Scientific title
A study of INT-747 (6-ethyl chenodeoxycholic acid [6-ECDCA]) in combination with ursodeoxycholic acid (UDCA [URSO®]) in patients with primary biliary cirrhosis (PBC)
Acronym
Study hypothesis
The primary hypothesis is that INT-747 will cause a reduction in alkaline phosphatase (AP) levels in primary biliary cirrhosis (PBC) patients, over a 12 week treatment period, as compared to placebo.
Ethics approval
Ethics approval received from:
1. USA: Institutional Review Board, Beth Israel Medical Centre on the 2nd October 2007 (ref: 133-07)
2. Canada: University of Toronto, University Health Network Research Ethics Board on the 10th June 2008 (ref: 07-0624-A)
Ethics approval received from (as of 09/12/2009):
3. Austria: Ethikkommission der Medizinischen Universität Graz on the 1st October 2008 (ref: 19-316 ex 07/09)
4. France: CPP Ile de France VI on the 27th October 2008 (ref: 85-08)
5. Germany: Ethik-Kommission der Medizinischen Hochschule Hannover on the 17th December 2008 (ref: 5162M)
6. Spain: Comitè Ètic Investigació Clínica on the 19th September 2008 (ref: 747-202)
Ethics approval pending from:
7. UK: Multicentre Research Ethics Committee (MREC)
8. The Netherlands
9. Italy
All other centres within recruiting countries will seek ethics approval before recruiting participants.
Study design
Treatment, randomised, double blind (subject, investigator), placebo controlled, parallel assignment, safety/efficacy study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the sponsor details to request a patient information sheet
Condition
Primary biliary cirrhosis
Intervention
1. Experimental treatment: INT-747 10 mg orally po once daily (QD)
2. Experimental treatment: INT-747 25 mg po QD
3. Experimental treatment INT-747 50 mg po QD
4. Matched placebo comparator: placebo po QD
Screening can last up to 4 weeks. Treatment is 12 weeks. Follow up after treatment is 2 weeks. Ursodeoxycholic acid (UDCA) treatment is prescribed by each patient's physician; the UDCA dose and timing of its administration each day is determined by each patient's physician (not by the protocol).
Intervention type
Drug
Phase
Not Applicable
Drug names
INT-747 (6-ethyl chenodeoxycholic acid [6-ECDCA]), ursodeoxycholic acid (UDCA [URSO®])
Primary outcome measure
To assess the effects of INT-747 on:
1. Alkaline phosphatase (AP) levels
2. Safety
Time frame: 12 weeks
Secondary outcome measures
1. To assess the effects of INT-747 on:
1.1. Hepatocellular injury and liver function
1.2. Disease-specific and general health symptoms
1.3. Biomarkers of hepatic inflammation and fibrosis
2. Plasma trough concentrations of INT-747 and its major, known metabolites
Time frame: 12 weeks
Overall trial start date
01/11/2007
Overall trial end date
02/12/2010
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Male or female age 18 to 70 years
2. Stable dose of ursodeoxycholic acid (UDCA [URSO®]) for at least six months prior to screening
3. Female patients must be post-menopausal, surgically sterile, or prepared to use two methods of contraception with all sexual partners during the study and for 14 days after the end of dosing
4. Male patients must be prepared to use two methods of contraception with all sexual partners during the study and for 14 days after the end of the dosing
5. Proven or likely PBC, as demonstrated by the patient presenting with at least two of the following three diagnostic factors:
5.1. History of increased AP levels for at least 6 months prior to Day 0
5.2. Positive antimitochondrial antibody (AMA) titre (greater than 1:40 titre on immunofluorescence or M2 positive by enzyme-linked immunosorbent assay [ELISA]) or PBC-specific antinuclear antibodies (antinuclear dot and nuclear rim positive)
5.3. Liver biopsy consistent with PBC
6. Screening AP value between 1.5 and 10 x upper limit of normal (ULN)
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
140
Participant exclusion criteria
1. Administration of the following drugs at any time during the three months prior to screening for the study:
1.1. Colchicine
1.2. Methotrexate
1.3. Azathioprine
1.4. Systemic corticosteroids
2. Screening conjugated (direct) bilirubin greater than 2 x ULN
3. Screening alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 5 x ULN
4. Screening serum creatinine greater than 133 µmol/L (1.5 mg/dL)
5. History or presence of hepatic decompensation (e.g., variceal bleeds, encephalopathy, or poorly controlled ascites)
6. History or presence of other concomitant liver diseases including hepatitis due to hepatitis B or C virus (HBV, HCV) infection, primary sclerosing cholangitis (PSC), alcoholic liver disease, definite autoimmune liver disease or biopsy proven nonalcoholic steatohepatitis (NASH)
7. Pregnancy
Recruitment start date
01/11/2007
Recruitment end date
02/12/2010
Locations
Countries of recruitment
Austria, Canada, France, Germany, Italy, Netherlands, Spain, United Kingdom, United States of America
Trial participating centre
Intercept Pharmaceuticals
San Diego
92122
United States of America
Sponsor information
Organisation
Intercept Pharmaceuticals (USA)
Sponsor details
4370 La Jolla Village Drive
Suite 1050
San Diego
92122
United States of America
+1 (0)858 652 6800
csciacca@interceptpharma.com
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
Genextra S.p.A. (Italy)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Visium (USA)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
JAFCO Life Science Investment (Japan)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
See https://clinicaltrials.gov/ct2/show/results/NCT00550862
Publication list
2015 results in: https://www.ncbi.nlm.nih.gov/pubmed/25500425