Clinical trial NCT00570765: Study of INT-747 as Monotherapy in Participants With Primary Biliary Cirrhosis (PBC)
Official title: A Study of INT-747 (6-ECDCA) Monotherapy in Patients With Primary Biliary Cirrhosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Liver Cirrhosis, Biliary
Lead sponsor: Intercept Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2007-12-11
Enrollment: 60
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 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.

Detailed description: The study included 2 phases: a 3-month randomized, double-blind (DB), placebo-controlled, parallel group phase, followed by a long-term safety extension (LTSE). The planned duration of the LTSE phase was country-specific, ranging from 108 months to indefinitely. On-site visits occurred at least every 6 months.

Following completion of the 3-month DB phase, participants who continued to meet protocol requirements were given the opportunity to enroll in the LTSE phase of the study at selected study sites. The participants who enrolled in the LTSE phase started OCA administration, from a starting dose (10 or 50 milligrams \[mg\]) based on the dose of OCA or placebo received in the DB phase or on the timing of entry into the LTSE phase.

Because the LTSE phase was not planned in the original study design, participants had varied gaps between the end of the DB phase and the start of the LTSE phase. Moreover, some participants initiated ursodeoxycholic acid during the course of that break.

Eligibility criteria: Inclusion Criteria:

* 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).

Exclusion Criteria:

* 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.

Primary outcomes:
measure: DB Phase: Mean Percent Change In Serum Alkaline Phosphatase (ALP) From Baseline To Day 85
timeFrame: Baseline, Day 85
Secondary outcomes:
measure: DB Phase: Mean Percent Change In Gamma-glutamyl Transferase (GGT) From Baseline To Day 85
timeFrame: Baseline, Day 85
measure: DB Phase: Mean Percent Change In Alanine Transaminase (ALT) From Baseline To Day 85
timeFrame: Baseline, Day 85
measure: DB: Plasma Trough Concentrations Of OCA And Its Major, Known Metabolites
timeFrame: 12 weeks
measure: DB Phase: Mean Percent Change In Conjugated Bilirubin From Baseline To Day 85
timeFrame: Baseline, Day 85
measure: LTSE Phase: Median Percent Change In Serum ALP From Baseline To Month 24, Month 48, Month 72, And Last Available Visit
timeFrame: Baseline (DB), Month 24, Month 48, Month 72, Last Available Visit (up to 96 months)
measure: LTSE Phase: Mean Percent Change In Serum ALP From Baseline To Month 24, Month 48, Month 72, And Last Available Visit
timeFrame: Baseline (DB), Month 24, Month 48, Month 72, Last Available Visit (up to 96 months)
measure: LTSE: Median Percent Change In GGT From Baseline To Last Available Visit
timeFrame: Baseline (DB), Last Available Visit (up to 96 months)
measure: LTSE: Mean Percent Change In GGT From Baseline To Last Available Visit
timeFrame: Baseline (DB), Last Available Visit (up to 96 months)
measure: LTSE: Median Percent Change In ALT From Baseline To Last Available Visit
timeFrame: Baseline (DB), Last Available Visit (up to 96 months)
measure: LTSE: Mean Percent Change In ALT From Baseline To Last Available Visit
timeFrame: Baseline (DB), Last Available Visit (up to 96 months)
measure: LTSE: Median Percent Change In Conjugated Bilirubin From Baseline To Last Available Visit
timeFrame: Baseline (DB), Last Available Visit (up to 96 months)
measure: LTSE: Mean Percent Change In Conjugated Bilirubin From Baseline To Last Available Visit
timeFrame: Baseline (DB), Last Available Visit (up to 96 months)
measure: LTSE: Median Percent Change In Total Bilirubin From Baseline To Last Available Visit
timeFrame: Baseline (DB), Last Available Visit (up to 96 months)
measure: LTSE: Mean Percent Change In Total Bilirubin From Baseline To Last Available Visit
timeFrame: Baseline (DB), Last Available Visit (up to 96 months)
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Henry Ford
state: Michigan
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Graz
country: Austria
facility: Karls-Franzens University
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Toronto
country: Canada
facility: University of Toronto
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: Paris
country: France
facility: Hopital Saint-Antoine
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: 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: Jarrow
country: United Kingdom
facility: Sunderland Research Ethics Committee
city: Newcastle Upon Tyne
country: United Kingdom
facility: University Upon Tyne/Newcastle
Study officials:
affiliation: Intercept Pharmaceuticals, Inc.
name: Christian Weyer, MD
role: STUDY_CHAIR
References:
citation: 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.