Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01865812
Recruitment Status : Completed
First Posted : May 31, 2013
Results First Posted : October 19, 2016
Last Update Posted : March 14, 2018
Sponsor:
Information provided by (Responsible Party):
Intercept Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE May 23, 2013
First Posted Date  ICMJE May 31, 2013
Results First Submitted Date  ICMJE August 25, 2016
Results First Posted Date  ICMJE October 19, 2016
Last Update Posted Date March 14, 2018
Study Start Date  ICMJE November 2013
Actual Primary Completion Date August 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 28, 2016)
  • Absolute Change From Baseline in High-density Lipoprotein (HDL) Cholesterol Concentration [ Time Frame: Baseline, Week 8 ]
  • Absolute Change From Baseline in High-density Lipoprotein (HDL) Particle Size [ Time Frame: Baseline, Week 8 ]
  • Absolute Change From Baseline in High-density Lipoprotein (HDL) Particle Concentration [ Time Frame: Baseline, Week 8 ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 28, 2013)
Change from baseline in High-density lipoprotein (HDL) Metabolism [ Time Frame: Week 4, Week 8 and Week 12 ]
HDL metabolism will be assessed by measuring HDL cholesterol concentration, HDL particle size and number.
Change History Complete list of historical versions of study NCT01865812 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: May 28, 2013)
  • Change from baseline in Lipoprotein Metabolism [ Time Frame: Week 4, Week 8 and Week 12 ]
    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 ]
    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 Cholesterylester transfer protein (CETP) activity.
    • pre-β1 HDL concentration
    • macrophage cholesterol efflux
  • Pharmacokinetic parameters of OCA and OCA conjugates [ Time Frame: Week 8 ]
    In a subset of patients who agree to participate, non-compartmental pharmacokinetic parameters of OCA and its conjugates will be assessed.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: May 28, 2013)
  • Fasting OCA and OCA Conjugates [ Time Frame: Week 8 ]
  • Change from baseline in fibroblast growth factor 19 (FGF-19) [ Time Frame: Week 4, Week 8 and Week 12 ]
  • Change from baseline in Lipoprotein X [ Time Frame: Week 4, Week 8 and Week 12 ]
 
Descriptive Information
Brief Title  ICMJE Phase 2 Study on Effects of Obeticholic Acid (OCA) on Lipoprotein Metabolism in Subjects With Primary Biliary Cirrhosis
Official Title  ICMJE A Phase 2 Clinical Trial Investigating the Effects of Obeticholic Acid on Lipoprotein Metabolism in Subjects With Primary Biliary Cirrhosis
Brief Summary 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.
Detailed Description This was a phase 2, open-label, multicenter study evaluating the effects of OCA on lipoprotein metabolism in subjects with PBC; in particular, OCA's effects on high density lipoprotein (HDL) cholesterol. Nuclear magnetic resonance (NMR) spectroscopy was utilized to quantify the changes in lipoprotein particle sizes and concentrations. Components of reverse cholesterol transport were also assessed.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Primary Biliary Cirrhosis
Intervention  ICMJE 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). After completion of the 8 week Primary Treatment Phase of the study and the 4 week follow up period, during which time subjects do not take OCA, all eligible subjects will be offered the opportunity to enter an open label long term safety extension phase, during which they will receive 10 mg OCA daily for up to 2 years.
Other Name: 6α-ethyl chenodeoxycholic acid (6-ECDCA); INT-747
Study Arms  ICMJE Experimental: OCA: 10 mg
obeticholic acid, oral administration, 10 mg, 8 weeks
Intervention: Drug: obeticholic acid (OCA)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 25, 2016)
26
Original Estimated Enrollment  ICMJE
 (submitted: May 28, 2013)
25
Actual Study Completion Date  ICMJE September 2016
Actual Primary Completion Date August 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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, 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 (HMG CoA) 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 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01865812
Other Study ID Numbers  ICMJE 747-205
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Intercept Pharmaceuticals
Study Sponsor  ICMJE Intercept Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: David Shapiro, MD Intercept Pharmaceuticals
PRS Account Intercept Pharmaceuticals
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP