ABT-335 (Choline Fenofibrate) Reverse Cholesterol Transport (RCT) Study

This study has been completed.
Sponsor:
Information provided by:
Radiant Research
ClinicalTrials.gov Identifier:
NCT00673881
First received: May 5, 2008
Last updated: March 25, 2011
Last verified: March 2011
  Purpose

The objectives of the study are:

  1. To evaluate the effect of ABT-335 (choline fenofibrate) on several parameters of RCT (reverse cholesterol transport) in men and post-menopausal women diagnosed with dyslipidemia (i.e., low high-density lipoprotein [HDL] cholesterol levels and elevated triglyceride [TG] concentrations).
  2. To evaluate longitudinal changes in several parameters of RCT in subjects with low HDL.
  3. To obtain pilot data for power calculations for subsequent comparative study.

Condition Intervention Phase
Dyslipidemia
Drug: choline fenofibrate
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: ABT-335 (Choline Fenofibrate)Reverse Cholesterol Transport (RCT) Study

Resource links provided by NLM:


Further study details as provided by Radiant Research:

Primary Outcome Measures:
  • Mean Change in Calculated Low Density Lipoprotein Cholesterol [ Time Frame: baseline to 12 weeks ] [ Designated as safety issue: No ]
    Mean change in calculated LDL, baseline (average Day 0, 1 10) to end-of-treatment (12 weeks treatment,average Day 95)

  • Mean Change in Plasma Triglycerides [ Time Frame: baseline to 12 weeks ] [ Designated as safety issue: No ]
    Change in plasma triglyceride, baseline (average Day 0, 1 10) to end-of-treatment (12 weeks treatment,Day 95)

  • Mean Change in High Density Lipoprotein Cholesterol [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Mean change in plasma high density plasma lipoprotein cholesterol (HDL-C)baseline (average Day 0, 1 10) to end-of-treatment (12 weeks treatment,Day 95)

  • Total Cholesterol [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Mean Change in total cholesterol from baseline to End-of-treatment (Day 95)


Secondary Outcome Measures:
  • Plasma Cholesterol Efflux [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Change in efflux rate from baseline to end-of-treatment. The efflux rate of cholesterol from peripheral tissues into the plasma was measured as mg/kg/hr. An IV infusion of [13C2] cholesterol mixed in 10% Intralipid® or Liposyn® and 10 % ethanol was given piggy-backed into normal saline over 24 hours. This was used to determine rate of appearance (Ra) cholesterol, measured by dilution of infused [13C2] cholesterol during the plateau phase of plasma enrichment (approximately the last 4 hours of the infusion), as well as to provide the plasma cholesterol traced into biliary sterols.

  • Change in Plasma Cholesterol Ester Fractional Catabolic Rate (FCR) [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Change in FCR from baseline to end-of-treatment (12 weeks)

  • Percent Change in de Novo Cholesterol Synthesis [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Plasma DNC was measured three times from blood draws on the 3 visits in the 10 day period following the isotope infusion at baseline and again at end-of-treatment at 12 weeks, and expressed in percent. Change from baseline to end-of-treatment expressed as percent.

  • Change in Neutral Sterol Excretion [ Time Frame: baseline to 12 weeks ] [ Designated as safety issue: No ]
    The excretion rate of fecal neutral and acidic sterols was measured as mg/day, for each individual three times during the 10 day period following the isotope infusions at baseline and end-of-treatment.

  • Change in Bile Acid Excretion [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Change in bile acid excretion from baseline to end-of-treatment

  • Neutral Sterol Endogenous Excretion [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Change in neutral sterol endogenous excretion from baseline to end-of-treatment

  • Endogenous Bile Acid Excretion [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Change in endogenous bile acid excretion from baseline to end-of-treatment


Enrollment: 25
Study Start Date: March 2008
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Abt-335
ABT-335 (choline fenofibrate)
Drug: choline fenofibrate
135 mg choline fenofibrate daily(oral, capsule)
Other Name: ABT-335

Detailed Description:

This trial assesses the effects of ABT-335 on RCT as measured by cholesterol efflux or rate of appearance of cholesterol (Ra in mg/kg/hr), cholesterol excretion (%/day), RCT efflux (mg/kg/day) and de novo cholesterol synthesis (%) during a baseline period (7 days) and during a treatment period (94 days).

The goal of using RCT to reverse atherosclerosis is to increase the rate of cholesterol export or "efflux" from the tissues and plaques. An increase in this cholesterol efflux rate should shrink arterial plaques by decreasing their static accumulation of cholesterol. While some currently marketed drugs have a positive impact on RCT by increasing the rate of cholesterol excretion from the body, no drug has yet been approved to increase the rate of cholesterol efflux from the tissues

  Eligibility

Ages Eligible for Study:   21 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Male, non-smoker, 21 - 75 years of age inclusive.
  2. Female, non-smoker, 40 - 75 years of age inclusive.
  3. Post-menopausal women, as defined by lack of menses for at least 2 years and age > 55, OR history of documented bilateral surgical oophorectomy, confirmed with an elevated follicle-stimulating hormone (FSH) at screening.
  4. HDL concentration (≤ 50 mg/dl women, ≤ 40mg/dl men)
  5. TG concentration 150-500 mg/dl, inclusive
  6. Ability to give informed consent

Exclusion Criteria:

  1. Subject has history of diabetes mellitus, active hepatitis, gall bladder disease, gastric bypass surgery, or clinically significant abnormalities on screening (prestudy) physical examination or laboratory tests.
  2. Screening laboratory tests with hematocrit <30%, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2X upper limit of normal, abnormal thyroid-stimulating hormone (TSH), fasting glucose ≥126 mg/dl.
  3. Renal impairment with creatinine clearance < 80 ml/min.
  4. Treatment within the last 6 months with drugs known to alter lipid metabolism including beta blockers, thiazide diuretics, bile acid resins, ezetimibe, fibrates, niacin, and fish oils (see Appendix 1). Washout of fibrates is not permitted.
  5. Treatment with drugs known to interact with ABT-335, e.g., warfarin (see Appendix 1).
  6. Treatment with HMG CoA reductase inhibitors (statins) within the past 4 weeks (see Appendix 1).
  7. History of allergy to egg or soy products.
  8. History of coronary heart disease (CHD), stroke or revascularization procedure in the six months prior to Visit 1.
  9. Current or recent history (past 12 months) of drug abuse or alcohol abuse. Alcohol abuse will be defined as >14 drinks per week (1 drink = 12 oz beer, 5 oz wine, or 1.5 oz hard liquor).
  10. Participation in another clinical trial or exposure to any investigational agent within 30 days before visit 1.
  11. Individual has a condition the Principal Investigator believes would interfere with his/her ability to provide informed consent, comply with study instructions, or which might confound the interpretation of the study results or put the subject at undue risk.
  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: NCT00673881

Locations
United States, Illinois
Radiant Research, 515 N State St, #2700
Chicago, Illinois, United States, 60610
Sponsors and Collaborators
Radiant Research
Investigators
Principal Investigator: Michael H Davidson, MD,FACC Radiant Research
  More Information

Additional Information:
No publications provided

Responsible Party: Michael H. Davidson,MD, FACC, Radiant Research
ClinicalTrials.gov Identifier: NCT00673881     History of Changes
Other Study ID Numbers: ABT-335-001
Study First Received: May 5, 2008
Results First Received: January 24, 2011
Last Updated: March 25, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Choline
Fenofibrate
Lipotropic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Gastrointestinal Agents
Therapeutic Uses
Lipid Regulating Agents
Nootropic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 28, 2014