Study of INT-747 as Monotherapy in Participants With Primary Biliary Cirrhosis (PBC)

NCT00570765 | Completed Phase 2 Results DMC

• 2 other identifiers: 747-2012007-001424-12
• Study Type: interventional
• Target: 60
• Locations: 7 countries
• Sites: 21

Brief Summary

The primary hypothesis was that obeticholic acid (OCA) will cause a reduction in alkaline phosphatase levels in PBC participants, over a 12-week treatment period, as compared to placebo.

Conditions

Liver Cirrhosis, Biliary

Outcome Measures

Primary Outcomes (1)

• DB Phase: Mean Percent Change In Serum Alkaline Phosphatase (ALP) From Baseline To Day 85

  The percent change in serum ALP from baseline to Day 85 is reported. The baseline value used was the mean of the pretreatment Screening and Day 0 evaluations.

  Baseline, Day 85

Secondary Outcomes (14)

• DB Phase: Mean Percent Change In Gamma-glutamyl Transferase (GGT) From Baseline To Day 85

  Baseline, Day 85

• DB Phase: Mean Percent Change In Alanine Transaminase (ALT) From Baseline To Day 85

  Baseline, Day 85

• DB: Plasma Trough Concentrations Of OCA And Its Major, Known Metabolites

  12 weeks

• DB Phase: Mean Percent Change In Conjugated Bilirubin From Baseline To Day 85

  Baseline, Day 85

• LTSE Phase: Median Percent Change In Serum ALP From Baseline To Month 24, Month 48, Month 72, And Last Available Visit

  Baseline (DB), Month 24, Month 48, Month 72, Last Available Visit (up to 96 months)

Study Arms (4)

DB OCA 10 mg

EXPERIMENTAL

OCA 10 mg for 3 months during the DB phase.

Drug: Obeticholic Acid (OCA)

DB OCA 50 mg

EXPERIMENTAL

OCA 50 mg for 3 months during the DB phase.

Drug: Obeticholic Acid (OCA)

DB OCA Placebo

PLACEBO COMPARATOR

Matching placebo for 3 months during the DB phase.

Drug: Placebo

LTSE OCA Total

EXPERIMENTAL

After completion of the 3-month DB phase, all eligible participants were offered the opportunity to enter an open-label LTSE for up to 96 months beginning at 10 mg OCA. Doses up to 50 mg daily were evaluated.

Drug: Obeticholic Acid (OCA)

Interventions

Placebo DRUG

Matching placebo tablets were administered orally once daily.

DB OCA Placebo

Obeticholic Acid (OCA) DRUG

Starting dose of 10 or 50 mg administered orally once daily, followed by dose titration planned from 10 mg to 25 mg to 50 mg once daily, which could be modified for safety and tolerability issues or to achieve adequate therapeutic response.

Also known as: INT-747, 6α-ethyl-chenodeoxycholic acid (6-ECDCA)

DB OCA 10 mg; DB OCA 50 mg; LTSE OCA Total

Eligibility Criteria

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

You may qualify if:

• Female participants must be postmenopausal, surgically sterile, or if premenopausal, be prepared to use 1 effective method of contraception with all sexual partners during the study and for 14 days after the end of dosing.
• Male participants must be prepared to use 1 effective method of contraception with all sexual partners during the study during the study unless they had a prior vasectomy.
• Proven or likely PBC, as demonstrated by the participant presenting with at least 2 of the following 3 diagnostic factors:
• History of increased alkaline phosphatase (ALP) levels for at least 6 months;
• Positive antimitochondrial antibody titer (\>1:40 titer on immunofluorescence or M2 positive by enzyme-linked immunosorbent assay) or PBC-specific antinuclear antibodies (antinuclear dot and nuclear rim positive);
• Liver biopsy consistent with PBC
• Screening ALP level between 1.5 and 10 × upper limit of normal (ULN).

You may not qualify if:

• Administration of the following drugs at any time during the 3 months prior to screening for the study: ursodeoxycholic acid, colchicine, methotrexate, azathioprine, or systemic corticosteroids.
• Screening conjugated (direct) bilirubin \>2 × ULN.
• Screening alanine aminotransferase or aspartate aminotransferase \>5 × ULN.
• Screening serum creatinine \>133 micromoles/liter (1.5 mg/deciliter).
• History or presence of hepatic decompensation (for example, variceal bleeds, encephalopathy, or poorly controlled ascites).
• History or presence of other concomitant liver diseases including hepatitis due to hepatitis B or C virus infection, primary sclerosing cholangitis, alcoholic liver disease, definite autoimmune liver disease or biopsy proven nonalcoholic steatohepatitis.
• Pregnancy.

Sponsors & Collaborators

• Intercept Pharmaceuticals: lead

Study Sites (21)

Henry Ford

Detroit, Michigan, 48202, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98105, United States

Location

Karls-Franzens University

Graz, 8036, Austria

Location

University of Alberta

Edmonton, Alberta, T6G 1K8, Canada

Location

University of Toronto

Toronto, Ontario, M5T 1S8, Canada

Location

Centre de Recherche du CHUM / University of Montreal

Montreal, Quebec, H2L 3R4, Canada

Location

Hopital de l'Hotel Dieu

Lyon, 69288, France

Location

Hopital Saint-Antoine

Paris, 75012, France

Location

Johann Wolfgang Goethe University

Frankfurt, 60590, Germany

Location

University Medical Centre Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Medical School of Hannover

Hanover, 30625, Germany

Location

University of Munich

Munich, 81377, Germany

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

Sunderland Research Ethics Committee

Jarrow, NE32 3DT, United Kingdom

Location

University Upon Tyne/Newcastle

Newcastle upon Tyne, NE2 4HH, United Kingdom

Location

Related Publications (1)

• Kowdley KV, Luketic V, Chapman R, Hirschfield GM, Poupon R, Schramm C, Vincent C, Rust C, Pares A, Mason A, Marschall HU, Shapiro D, Adorini L, Sciacca C, Beecher-Jones T, Bohm O, Pencek R, Jones D; Obeticholic Acid PBC Monotherapy Study Group. A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis. Hepatology. 2018 May;67(5):1890-1902. doi: 10.1002/hep.29569. Epub 2018 Jan 29.

  PMID: 29023915 BACKGROUND

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Interventions

obeticholic 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

Limitations and Caveats

Limitations of the study include the use of ursodeoxycholic acid that disallowed meeting key inclusion/exclusion criteria, a short double-blind phase, and the reason participants were not receiving ursodeoxycholic acid at baseline was not captured.

Results Point of Contact

• Title: Medical Information
• Organization: Intercept Pharmaceuticals, Inc.

medinfo@interceptpharma.com

844-782-4278

Study Officials

• Christian Weyer, MD

  Intercept Pharmaceuticals, Inc.

  STUDY CHAIR

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: December 7, 2007
• First Posted: December 11, 2007
• Study Start: January 17, 2008
• Primary Completion: September 21, 2010
• Study Completion: September 25, 2017
• Last Updated: June 22, 2021
• Results First Posted: July 7, 2011

Record last verified: 2021-05

Locations

US (4); CA (3); FR (2); ES (1); GB (6); AU (1); DE (4)