Phase 2 Study on Effects of Obeticholic Acid (OCA) on Lipoprotein Metabolism in Participants With Primary Biliary Cirrhosis

NCT ID: NCT01865812

Last Updated: 2022-08-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-03
• Study Completion Date: 2016-09-12

Brief Summary

The purpose of this study was to determine if OCA had an effect on cholesterol levels in the blood in participants with primary biliary cirrhosis (PBC).

Detailed Description

This was a phase 2, open-label, multicenter study evaluating the effects of OCA on lipoprotein metabolism in participants with PBC; in particular, OCA's effects on high-density lipoprotein cholesterol. Nuclear magnetic resonance spectroscopy was utilized to quantify the changes in lipoprotein particle sizes and concentrations. Components of reverse cholesterol transport were also assessed.

Conditions

Primary Biliary Cirrhosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

OCA: 10 mg

Obeticholic acid, oral administration, 10 milligrams (mg), 8 weeks

Group Type: EXPERIMENTAL

Obeticholic Acid

Intervention Type: DRUG

All participants were treated with OCA (oral administration, 10 mg, once daily \[QD\]) for 8 weeks and continued their prestudy dose of ursodeoxycholic acid (UDCA). After completion of the 8-week Primary Treatment Phase of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter an open-label, long-term safety extension phase, during which they could receive 10 mg OCA QD for up to 2 years.

Interventions

Obeticholic Acid

All participants were treated with OCA (oral administration, 10 mg, once daily \[QD\]) for 8 weeks and continued their prestudy dose of ursodeoxycholic acid (UDCA). After completion of the 8-week Primary Treatment Phase of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter an open-label, long-term safety extension phase, during which they could receive 10 mg OCA QD for up to 2 years.

Intervention Type: DRUG

Other Intervention Names

6α-Ethyl chenodeoxycholic acid (6-ECDCA); INT-747

Eligibility Criteria

Inclusion Criteria

1. Definite or probable PBC diagnosis as demonstrated by the presence of ≥ 2 of the following 3 diagnostic factors:

• History of elevated alkaline phosphatase levels for at least 6 months
• A positive anti-microbial antibody (AMA) titer or, if AMA negative or in low titer (<1:80), PBC-specific antibodies
• Liver biopsy consistent with PBC

2. Taking UDCA for at least 12 months (stable dose for ≥ 3 months) prior to Day 0 or unable to tolerate UDCA (no UDCA for ≥ 3 months prior to Day 0).

3. Contraception: Female participants must have been postmenopausal, surgically sterile, or if premenopausal, were prepared to use ≥ 1 effective (≤ 1% failure rate) method of contraception during the trial and until at least 30 days after the last dose of Investigational Product.

4. Must have provided written informed consent and agreed to comply with the trial protocol.

Exclusion Criteria

1. Participants with decompensated PBC (as determined by the Investigator).

2. Severe pruritus or systemic treatment for pruritus (for example, treatment with bile acid sequestrants or rifampicin) within 2 months of Day 0.

3. History or presence of other significant liver diseases including:

• Active or chronic Hepatitis B or C virus infection
• Primary sclerosing cholangitis
• Alcoholic liver disease
• Definite autoimmune liver disease or overlap hepatitis
• Nonalcoholic steatohepatitis

Note: Participants with Gilbert's disease or those with a history of hepatitis B who were currently antigen negative and seroconverted were not considered exclusionary.

4. Uncontrolled diabetes or other uncontrolled or unstable medical condition that may have interfered with trial results.

5. Administration of any of the following medications as specified below:

• Prohibited 28 days prior to Day 0: bile acid sequestrants including cholestyramine, colesevelam, colestipol or omega-3 fatty acid containing dietary supplements
• Prohibited 3 months prior to Day 0 and throughout trial participation: serum-lipid modifying agents including 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, fenofibrate or other fibrates, nicotinic acid and derivatives, ezetimibe, Vitamin E (other than as standard dietary supplement)
• Prohibited 6 months prior to Day 0 and throughout the trial participation: azathioprine, colchicine, cyclosporine, methotrexate, mycophenolate mofetil, pentoxifylline; budesonide and other systemic corticosteroids; potentially hepatotoxic drugs (including α-methyl-dopa, sodium valproic acid, isoniazide, or nitrofurantoin)
• Prohibited 12 months prior to Day 0 and throughout the trial participation: antibodies or immunotherapy directed against interleukins or other cytokines or chemokines

6. Planned change in diet or exercise habits during participation in the trial.

7. Presence or history of clinically significant cardiac arrhythmias that may have prohibited the participant from participating in the trial.

8. If female: known pregnancy, or had a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating.

9. Recent (3 months prior to day 0) participation in another trial involving OCA or participation in another investigational trial (30 days prior to Day 0) and during the trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Intercept Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

George Harb, MD

Role: STUDY_DIRECTOR

Intercept Pharmaceuticals, Inc.

Locations

Scripps Clinic

La Jolla, California, United States

University of California, Davis Medical Center

Sacramento, California, United States

University of Miami

Miami, Florida, United States

Indiana University Medical Center

Indianapolis, Indiana, United States

Beth Israel Medical Center

New York, New York, United States

McGuire DVAMC

Richmond, Virginia, United States

Swedish Medical Center

Seattle, Washington, United States

Countries

United States

Other Identifiers

747-205

Identifier Type: -

Identifier Source: org_study_id