Study of INT-747 in combination with ursodeoxycholic acid (UDCA [URSO®]) in patients with primary biliary cirrhosis (PBC)

ISRCTN ISRCTN67465025
DOI https://doi.org/10.1186/ISRCTN67465025
ClinicalTrials.gov number NCT00550862
Secondary identifying numbers 747-202
Submission date
03/07/2008
Registration date
13/08/2008
Last edited
27/04/2018
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Digestive System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Erin Castelloe
Scientific

Clinical Consultant - Pharmacovigilance
4370 La Jolla Village Drive
Suite 1050
San Diego
92122
United States of America

Phone +1 (0)858 354 6441
Email ecastelloe@interceptpharma.com

Study information

Study designTreatment, randomised, double blind (subject, investigator), placebo controlled, parallel assignment, safety/efficacy study
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the sponsor details to request a patient information sheet
Scientific titleA study of INT-747 (6-ethyl chenodeoxycholic acid [6-ECDCA]) in combination with ursodeoxycholic acid (UDCA [URSO®]) in patients with primary biliary cirrhosis (PBC)
Study objectivesThe 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(s)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.
Health condition(s) or problem(s) studiedPrimary biliary cirrhosis
Intervention1. 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 typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)INT-747 (6-ethyl chenodeoxycholic acid [6-ECDCA]), ursodeoxycholic acid (UDCA [URSO®])
Primary outcome measureTo assess the effects of INT-747 on:
1. Alkaline phosphatase (AP) levels
2. Safety

Time frame: 12 weeks
Secondary outcome measures1. 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 study start date01/11/2007
Completion date02/12/2010

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants140
Key inclusion criteria1. 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)
Key exclusion criteria1. 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
Date of first enrolment01/11/2007
Date of final enrolment02/12/2010

Locations

Countries of recruitment

  • Austria
  • Canada
  • France
  • Germany
  • Italy
  • Netherlands
  • Spain
  • United Kingdom
  • United States of America

Study participating centre

Intercept Pharmaceuticals
San Diego
92122
United States of America

Sponsor information

Intercept Pharmaceuticals (USA)
Industry

4370 La Jolla Village Drive
Suite 1050
San Diego
92122
United States of America

Phone +1 (0)858 652 6800
Email csciacca@interceptpharma.com
Website http://www.interceptpharma.com
ROR logo "ROR" https://ror.org/01sx6jc36

Funders

Funder type

Industry

Genextra S.p.A. (Italy)

No information available

Visium (USA)

No information available

JAFCO Life Science Investment (Japan)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Basic results No No
Results article results 01/04/2015 Yes No

Editorial Notes

27/04/2018: Publication reference added.
22/03/2016: Added link to results - basic reporting.
15/01/2013: The overall trial end date was changed from 01/12/2008 to 02/12/2010.