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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Intercept Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01865812
First received: May 23, 2013
Last updated: June 19, 2014
Last verified: June 2014
  Purpose

The purpose of this study is to determine if obeticholic acid (OCA) has an effect on cholesterol levels in the blood in patients with PBC.


Condition Intervention Phase
Primary Biliary Cirrhosis
Drug: obeticholic acid (OCA)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Phase 2 Clinical Trial Investigating the Effects of Obeticholic Acid on Lipoprotein Metabolism in Subjects With Primary Biliary Cirrhosis

Resource links provided by NLM:


Further study details as provided by Intercept Pharmaceuticals:

Primary Outcome Measures:
  • Change from baseline in High-density lipoprotein (HDL) Metabolism [ Time Frame: Week 4, Week 8 and Week 12 ] [ Designated as safety issue: No ]
    HDL metabolism will be assessed by measuring HDL cholesterol concentration, HDL particle size and number.


Secondary Outcome Measures:
  • Change from baseline in Lipoprotein Metabolism [ Time Frame: Week 4, Week 8 and Week 12 ] [ Designated as safety issue: No ]

    Lipoprotein metabolism will be assessed by measuring the following:

    • concentrations of total cholesterol and triglycerides
    • Low-density lipoprotein (LDL) and very low density lipoprotein (VLDL) cholesterol concentrations, particle size and number
    • concentrations of apolipoprotein A (ApoA), apolipoprotein B (ApoB), apolipoprotein E (ApoE), and lipoprotein (a) [Lp(a)]

  • Change from baseline Reverse Cholesterol Transport [ Time Frame: Week 4, Week 8 and Week 12 ] [ Designated as safety issue: No ]

    Components of reverse cholesterol transport will also be assessed as part of the lipoprotein analysis. This will include measurements of:

    • HDL capacity to accept cholesterol measured by lecithin-cholesterol acyltransferase (LCAT) and Cholesterol ester transfer protein (CETP) activity.
    • pre-β1 HDL concentration
    • macrophage cholesterol efflux

  • Pharmacokinetic parameters of OCA and OCA conjugates [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    In a subset of patients who agree to participate, non-compartmental pharmacokinetic parameters of OCA and its conjugates (glyco-OCA and tauro-OCA) will be assessed.


Other Outcome Measures:
  • Fasting levels of OCA and Conjugates [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
  • Change from baseline in fibroblast growth factor 19 (FGF-19) [ Time Frame: Week 4, Week 8 and Week 12 ] [ Designated as safety issue: No ]
  • Change from baseline in Lipoprotein X [ Time Frame: Week 4, Week 8 and Week 12 ] [ Designated as safety issue: No ]
  • Markers of inflammation including: C-Reactive Protein, GlycA and GlycB [ Time Frame: Week 8 ] [ Designated as safety issue: No ]

Estimated Enrollment: 25
Study Start Date: November 2013
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: OCA: 10 mg
obeticholic acid, oral administration, 10mg, 8 weeks
Drug: obeticholic acid (OCA)
All subjects will be treated with OCA (oral administration, 10 mg, once daily) for 8 weeks and should continue their prestudy dose of ursodeoxycholic acid (UDCA).
Other Name: 6α-ethyl chenodeoxycholic acid (6-ECDCA); INT-747

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

    • History of elevated alkaline phosphatase (ALP) 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. Age ≥ 18 years
  3. 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)
  4. Contraception: Female subjects must be postmenopausal, surgically sterile, or if premenopausal, be 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.
  5. Must provide written informed consent and agree to comply with the trial protocol.

Exclusion Criteria:

  1. Subjects with decompensated PBC (as determined by the Investigator)
  2. Severe pruritus or systemic treatment for pruritus (e.g. 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 (HBV, HCV) infection
    • Primary sclerosing cholangitis (PSC)
    • Alcoholic liver disease
    • Definite autoimmune liver disease or overlap hepatitis
    • Nonalcoholic steatohepatitis (NASH)

    NOTE: Subjects with Gilbert's disease or those with a history of hepatitis B who are currently antigen negative and seroconverted should not be considered exclusionary

  4. Uncontrolled diabetes or other uncontrolled or unstable medical condition that may interfere with trial results
  5. Administration of any of the following medications as specified below:

    • Prohibited 28 days prior to Day 0: bile acid sequestrants (BAS) including cholestyramine, colesevelam, or colestipol
    • Prohibited 3 months prior to Day 0 and throughout trial participation: serum-lipid modifying agents including 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase inhibitors, fenofibrate or other fibrates, nicotinic acid and derivatives, ezetimibe, Vitamin E (other than as standard dietary supplement), omega-3 fatty acid containing dietary supplements
    • 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 prohibit the subject from participating in the trial
  8. If female: known pregnancy, or has 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01865812

Locations
United States, Florida
University of Miami
Miami, Florida, United States, 33136
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New York
Beth Israel Medical Center
New York, New York, United States, 10003
United States, Virginia
McGuire DVAMC
Richmond, Virginia, United States, 23249
United States, Washington
Virginia Mason Medical Center
Seattle, Washington, United States, 98034
Sponsors and Collaborators
Intercept Pharmaceuticals
Investigators
Study Director: David Shapiro, MD Intercept Pharmaceuticals
  More Information

No publications provided

Responsible Party: Intercept Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01865812     History of Changes
Other Study ID Numbers: 747-205
Study First Received: May 23, 2013
Last Updated: June 19, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Liver Cirrhosis, Biliary
Liver Cirrhosis
Fibrosis
Cholestasis, Intrahepatic
Cholestasis
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Liver Diseases
Pathologic Processes
Chenodeoxycholic Acid
Cathartics
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 11, 2014