Clinical trial NCT00550862: Study of INT 747 in Combination With URSO in Patients With Primay Biliary Cirrhosis (PBC)
Official title: A Study of INT 747 (6α-ethyl Chenodeoxycholic Acid (6-ECDCA)) in Combination With Ursodeoxycholic Acid (URSO®, UDCA) in Patients With Primary Biliary Cirrhosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Liver Cirrhosis, Biliary
Keywords: PBC, Primary Biliary Cirrhosis, Liver,
Lead sponsor: Intercept Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2007-10-30
Enrollment: 165
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary hypothesis is that INT-747 will cause a reduction in alkaline phosphatase levels in Primary Biliary Cirrhosis patients, over a 12 week treatment period, as compared to placebo.

Detailed description: None provided

Eligibility criteria: 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 prepared to use 2 methods of contraception with all sexual partners during the study and for 14 days after the end of dosing.
* Male patients must be prepared to use 2 methods of contraception with all sexual partners during the study and for 14 days after the end of the dosing.
* Proven or likely PBC, as demonstrated by the patient presenting with at least 2 of the following 3 diagnostic factors:

  1. History of increased AP levels for at least 6 months prior to Day 0
  2. Positive AMA titer (\>1:40 titer on immunofluorescence or M2 positive by ELISA) or PBC-specific antinuclear antibodies (antinuclear dot and nuclear rim positive)
  3. Liver biopsy consistent with PBC.
* Screening AP value between 1.5 and 10 × ULN.

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 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).
* Pregnancy.

Primary outcomes:
measure: Double-blind Phase: Percent Change From Baseline in Serum Alkaline Phosphatase (ALP)
timeFrame: Baseline and Up to Day 85
Secondary outcomes:
measure: Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels
timeFrame: Baseline and at Days 15, 29, 57 and 85
measure: Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
timeFrame: Baseline and at Days 15, 29, 57 and 85
measure: LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
timeFrame: Baseline and at 3, 6, 9 and 12 Months
measure: Double-blind Phase: Absolute Values for Albumin Levels
timeFrame: Baseline and at Days 15, 29, 57 and 85
measure: Double-blind Phase: Percent Change From Baseline in Albumin Levels
timeFrame: Baseline and at Days 15, 29, 57 and 85
measure: Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin
timeFrame: Baseline and at Days 15, 29, 57 and 85
measure: Double-blind Phase: Percent Change From Baseline in Conjugated (Direct) Bilirubin
timeFrame: Baseline and at Days 15, 29, 57 and 85
measure: LTSE Phase: Mean Percent Change From Baseline in Total and Conjugated (Direct) Bilirubin
timeFrame: Baseline and at 3, 6, 9 and 12 Months
measure: Double-blind Phase: Change From Baseline in Enhanced Liver Fibrosis (ELF) Score
timeFrame: Baseline and up to Day 85
measure: Double-blind Phase: Change From Baseline in HA, P3NP, and TIMP-1 Levels
timeFrame: Baseline and Up to Day 85
measure: Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: C-reactive Protein
timeFrame: Baseline and Up to Day 85
measure: Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: C-reactive Protein
timeFrame: Baseline and Up to Day 85
measure: Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Non-essential Fatty Acid (NEFA)
timeFrame: Baseline and Up to Day 85
measure: Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: NEFA
timeFrame: Baseline and Up to Day 85
measure: Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Tumor Necrosis Factor Alpha (TNF-alpha)
timeFrame: Baseline and Up to Day 85
measure: Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: TNF-alpha
timeFrame: Baseline and Up to Day 85
measure: Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: TNF-beta and Tumor Growth Factor Beta (TGF-beta)
timeFrame: Baseline and Up to Day 85
measure: Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: TNF-beta and TGF-beta
timeFrame: Baseline and Up to Day 85
measure: Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion
timeFrame: Baseline and Up to Day 85
measure: Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion
timeFrame: Baseline and Up to Day 85
measure: Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Immunoglobulin M (IgM)
timeFrame: Baseline and Up to Day 85
measure: Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: IgM
timeFrame: Baseline and Up to Day 85
measure: Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Osteopontin
timeFrame: Baseline and Up to Day 85
measure: Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: Osteopontin
timeFrame: Baseline and Up to Day 85
measure: Double-blind Phase: Absolute Values for Total Endogenous Bile Acids
timeFrame: Baseline and Up to Day 85
measure: Double-blind Phase: Change From Baseline in Total Endogenous Bile Acids
timeFrame: Baseline and Up to Day 85
measure: Double-blind Phase: Absolute Values for Fibroblast Growth Factor 19 (FGF19)
timeFrame: Baseline and Up to Day 85
measure: Double-blind Phase: Percent Change From Baseline Values for FGF19
timeFrame: Baseline and Up to Day 85
measure: Double-blind Phase: Change From Baseline to Day 85 in Quality of Life as Determined by Short Form-36 (SF-36) Scale
timeFrame: Baseline and Up to Day 85
measure: LTSE Phase: Absolute Values of Quality of Life as Determined by SF-36 Scale
timeFrame: Baseline and at 3, 6, 9 and 12 Months
measure: Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale
timeFrame: Baseline and at Days 29, 57 and 85
measure: LTSE Phase: Change From Baseline in Quality of Life as Determined by PBC-40 Scale
timeFrame: Baseline and at 6 and 12 months
measure: Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale
timeFrame: Baseline and at Days 29, 57 and 85
measure: Double-blind Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Day 85
measure: Double-blind Phase: Change From Baseline in Pruritus Visual Analog Scale (VAS)
timeFrame: Baseline and at Days 29, 57 and 85
measure: LTSE Phase: Number of Participants With TEAEs and SAEs
timeFrame: Up to 12 Months
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: U Florida Hepatology
state: Florida
city: Miami
country: United States
facility: University of Miami - Center for Liver Diseases
state: Florida
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Novi
country: United States
facility: Henry Ford Health Center Columbus
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: New York
country: United States
facility: Mt. Sinai School of Medicine
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Richmond
country: United States
facility: McGuire DVAMC
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Graz
country: Austria
facility: Karls-Franzens University
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Winnipeg
country: Canada
facility: University of Manitoba
state: Manitoba
city: Toronto
country: Canada
facility: University of Toronto Western Hospital
state: Ontario
city: Montreal
country: Canada
facility: Centre de Recherche du CHUM / University of Montreal
state: Quebec
city: Lyon
country: France
facility: Hopital de l'Hotel Dieu
city: Frankfurt
country: Germany
facility: Johann Wolfgang Goethe University
city: Hamburg
country: Germany
facility: University Medical Centre Hamburg-Eppendorf
city: Hannover
country: Germany
facility: Medical School of Hannover
city: Munich
country: Germany
facility: University of Munich
city: Amsterdam
country: Netherlands
facility: AMC University of Amsterdam
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Centre
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial
city: Edgbaston
country: United Kingdom
facility: Queen Elizabeth Medical Center
state: Birmingham
city: Hampstead
country: United Kingdom
facility: Royal Free Hospital
state: London
city: Headington
country: United Kingdom
facility: John Radcliffe Hospital
state: Oxford
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary
city: Newcastle Upon Tyne
country: United Kingdom
facility: University Upon Tyne/Newcastle
Study officials:
affiliation: Intercept Pharmaceuticals - Chief Medical Officer
name: David A Shapiro, MD
role: STUDY_DIRECTOR
References:
citation: Hirschfield GM, Mason A, Luketic V, Lindor K, Gordon SC, Mayo M, Kowdley KV, Vincent C, Bodhenheimer HC Jr, Pares A, Trauner M, Marschall HU, Adorini L, Sciacca C, Beecher-Jones T, Castelloe E, Bohm O, Shapiro D. Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid. Gastroenterology. 2015 Apr;148(4):751-61.e8. doi: 10.1053/j.gastro.2014.12.005. Epub 2014 Dec 11.