Study of INT 747 in Combination With URSO in Patients With Primay Biliary Cirrhosis (PBC)

NCT00550862 | Terminated Phase 2 Results DMC

• 1 other identifier: 747-202
• Study Type: interventional
• Target: 165
• Locations: 8 countries
• Sites: 32

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.

Conditions

Liver Cirrhosis, Biliary

Keywords

PBC, Primary Biliary Cirrhosis, Liver,

Outcome Measures

Primary Outcomes (1)

• Double-blind Phase: Percent Change From Baseline in Serum Alkaline Phosphatase (ALP)

  Blood samples were collected for the analysis of serum ALP. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Percent change from Baseline was calculated as Post Baseline minus Baseline value divided by Baseline value and multiplied by 100.

  Baseline and Up to Day 85

Secondary Outcomes (36)

• Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels

  Baseline and at Days 15, 29, 57 and 85

• Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels

  Baseline and at Days 15, 29, 57 and 85

• LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels

  Baseline and at 3, 6, 9 and 12 Months

• Double-blind Phase: Absolute Values for Albumin Levels

  Baseline and at Days 15, 29, 57 and 85

• Double-blind Phase: Percent Change From Baseline in Albumin Levels

  Baseline and at Days 15, 29, 57 and 85

Study Arms (4)

INT-747 10 mg

EXPERIMENTAL

INT-747 10 mg once daily in combination with URSO for 12 weeks.

Drug: INT-747; Drug: Ursodeoxycholic Acid (URSO)

INT-747 25 mg

EXPERIMENTAL

INT-747 25 mg once daily in combination with URSO for 12 weeks.

Drug: INT-747; Drug: Ursodeoxycholic Acid (URSO)

INT-747 50 mg

EXPERIMENTAL

INT-747 50 mg once daily in combination with URSO for 12 weeks.

Drug: INT-747; Drug: Ursodeoxycholic Acid (URSO)

Placebo

PLACEBO COMPARATOR

Placebo once daily in combination with URSO for 12 weeks.

Drug: INT-747; Drug: Ursodeoxycholic Acid (URSO); Drug: Placebo

Interventions

INT-747 DRUG

Once a day (QD) by mouth (PO)

Also known as: Obeticholic acid (OCA), 6-ECDCA

INT-747 10 mg; INT-747 25 mg; INT-747 50 mg; Placebo

Ursodeoxycholic Acid (URSO) DRUG

Stable dose for at least 6 months prior to screening. Dose as prescribed by physician.

Also known as: URSO, UDCA

INT-747 10 mg; INT-747 25 mg; INT-747 50 mg; Placebo

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Intercept Pharmaceuticals: lead

Study Sites (32)

U Florida Hepatology

Gainesville, Florida, 32610, United States

Location

University of Miami - Center for Liver Diseases

Miami, Florida, 33136, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Henry Ford Health Center Columbus

Novi, Michigan, 48377, United States

Location

Mayo Clinic

Rochester, Minnesota, 555905, United States

Location

Saint Louis University

St Louis, Missouri, 63104, United States

Location

Beth Israel Medical Center

New York, New York, 10003, United States

Location

Mt. Sinai School of Medicine

New York, New York, 10029, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

McGuire DVAMC

Richmond, Virginia, 23249, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Karls-Franzens University

Graz, A8036, Austria

Location

University of Calgary

Calgary, Alberta, T2N 4N1, Canada

Location

University of Alberta

Edmonton, Alberta, T5G 2X8, Canada

Location

University of Manitoba

Winnipeg, Manitoba, R3E 3P4, Canada

Location

University of Toronto Western Hospital

Toronto, Ontario, M5T2S8, Canada

Location

Centre de Recherche du CHUM / University of Montreal

Montreal, Quebec, H2X 1P1, Canada

Location

Hopital de l'Hotel Dieu

Lyon, 69288, France

Location

Johann Wolfgang Goethe University

Frankfurt, 60590, Germany

Location

University Medical Centre Hamburg-Eppendorf

Hamburg, D20246, Germany

Location

Medical School of Hannover

Hanover, 30623, Germany

Location

University of Munich

Munich, D81377, Germany

Location

AMC University of Amsterdam

Amsterdam, NL-1100, Netherlands

Location

Erasmus Medical Centre

Rotterdam, 3000, Netherlands

Location

Hospital Clinic i Provincial

Barcelona, 08036, Spain

Location

Queen Elizabeth Medical Center

Edgbaston, Birmingham, B15 2TH, United Kingdom

Location

Royal Free Hospital

Hampstead, London, NW3 2QG, United Kingdom

Location

John Radcliffe Hospital

Headington, Oxford, OX3 9DU, United Kingdom

Location

Royal Infirmary

Edinburgh, EH16 4SA, United Kingdom

Location

University Upon Tyne/Newcastle

Newcastle upon Tyne, NE2 4HH, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 25500425 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Interventions

obeticholic acid; Ursodeoxycholic Acid

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes

Results Point of Contact

• Title: Dr. David Shapiro
• Organization: Intercept Pharmaceuticals

dshapiro@interceptpharma.com

858-652-6800

Study Officials

• David A Shapiro, MD

  Intercept Pharmaceuticals - Chief Medical Officer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2007
• First Posted: October 30, 2007
• Study Start: October 1, 2007
• Primary Completion: August 1, 2009
• Study Completion: December 1, 2010
• Last Updated: February 6, 2024
• Results First Posted: January 23, 2012

Record last verified: 2024-01

Locations

GB (5); DE (4); NL (2); ES (1); AU (1); US (13); CA (5); FR (1)