Back to resultsABT-335 (Choline Fenofibrate) Reverse Cholesterol Transport (RCT) Study
Primary Purpose
Dyslipidemia
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
choline fenofibrate
Sponsored by
About this trial
This is an interventional treatment trial for Dyslipidemia
Eligibility Criteria
Inclusion Criteria:
- Male, non-smoker, 21 - 75 years of age inclusive.
- Female, non-smoker, 40 - 75 years of age inclusive.
- 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.
- HDL concentration (≤ 50 mg/dl women, ≤ 40mg/dl men)
- TG concentration 150-500 mg/dl, inclusive
- Ability to give informed consent
Exclusion Criteria:
- 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.
- 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.
- Renal impairment with creatinine clearance < 80 ml/min.
- 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.
- Treatment with drugs known to interact with ABT-335, e.g., warfarin (see Appendix 1).
- Treatment with HMG CoA reductase inhibitors (statins) within the past 4 weeks (see Appendix 1).
- History of allergy to egg or soy products.
- History of coronary heart disease (CHD), stroke or revascularization procedure in the six months prior to Visit 1.
- 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).
- Participation in another clinical trial or exposure to any investigational agent within 30 days before visit 1.
- 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.
Sites / Locations
- Radiant Research, 515 N State St, #2700
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Abt-335
Arm Description
ABT-335 (choline fenofibrate)
Outcomes
Primary Outcome Measures
Mean Change in Calculated Low Density Lipoprotein Cholesterol
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
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
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
Mean Change in total cholesterol from baseline to End-of-treatment (Day 95)
Secondary Outcome Measures
Plasma Cholesterol Efflux
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)
Change in FCR from baseline to end-of-treatment (12 weeks)
Percent Change in de Novo Cholesterol Synthesis
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
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
Change in bile acid excretion from baseline to end-of-treatment
Neutral Sterol Endogenous Excretion
Change in neutral sterol endogenous excretion from baseline to end-of-treatment
Endogenous Bile Acid Excretion
Change in endogenous bile acid excretion from baseline to end-of-treatment
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00673881
Brief Title
ABT-335 (Choline Fenofibrate) Reverse Cholesterol Transport (RCT) Study
Official Title
ABT-335 (Choline Fenofibrate)Reverse Cholesterol Transport (RCT) Study
Study Type
Interventional
2. Study Status
Record Verification Date
March 2011
Overall Recruitment Status
Completed
Study Start Date
March 2008 (undefined)
Primary Completion Date
May 2009 (Actual)
Study Completion Date
May 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Radiant Research
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The objectives of the study are:
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).
To evaluate longitudinal changes in several parameters of RCT in subjects with low HDL.
To obtain pilot data for power calculations for subsequent comparative study.
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dyslipidemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Abt-335
Arm Type
Experimental
Arm Description
ABT-335 (choline fenofibrate)
Intervention Type
Drug
Intervention Name(s)
choline fenofibrate
Other Intervention Name(s)
ABT-335
Intervention Description
135 mg choline fenofibrate daily(oral, capsule)
Primary Outcome Measure Information:
Title
Mean Change in Calculated Low Density Lipoprotein Cholesterol
Description
Mean change in calculated LDL, baseline (average Day 0, 1 10) to end-of-treatment (12 weeks treatment,average Day 95)
Time Frame
baseline to 12 weeks
Title
Mean Change in Plasma Triglycerides
Description
Change in plasma triglyceride, baseline (average Day 0, 1 10) to end-of-treatment (12 weeks treatment,Day 95)
Time Frame
baseline to 12 weeks
Title
Mean Change in High Density Lipoprotein Cholesterol
Description
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)
Time Frame
Baseline to 12 weeks
Title
Total Cholesterol
Description
Mean Change in total cholesterol from baseline to End-of-treatment (Day 95)
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Plasma Cholesterol Efflux
Description
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.
Time Frame
12 weeks
Title
Change in Plasma Cholesterol Ester Fractional Catabolic Rate (FCR)
Description
Change in FCR from baseline to end-of-treatment (12 weeks)
Time Frame
Baseline to 12 weeks
Title
Percent Change in de Novo Cholesterol Synthesis
Description
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.
Time Frame
Baseline to 12 weeks
Title
Change in Neutral Sterol Excretion
Description
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.
Time Frame
baseline to 12 weeks
Title
Change in Bile Acid Excretion
Description
Change in bile acid excretion from baseline to end-of-treatment
Time Frame
Baseline to 12 weeks
Title
Neutral Sterol Endogenous Excretion
Description
Change in neutral sterol endogenous excretion from baseline to end-of-treatment
Time Frame
12 weeks
Title
Endogenous Bile Acid Excretion
Description
Change in endogenous bile acid excretion from baseline to end-of-treatment
Time Frame
12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Male, non-smoker, 21 - 75 years of age inclusive.
Female, non-smoker, 40 - 75 years of age inclusive.
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.
HDL concentration (≤ 50 mg/dl women, ≤ 40mg/dl men)
TG concentration 150-500 mg/dl, inclusive
Ability to give informed consent
Exclusion Criteria:
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.
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.
Renal impairment with creatinine clearance < 80 ml/min.
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.
Treatment with drugs known to interact with ABT-335, e.g., warfarin (see Appendix 1).
Treatment with HMG CoA reductase inhibitors (statins) within the past 4 weeks (see Appendix 1).
History of allergy to egg or soy products.
History of coronary heart disease (CHD), stroke or revascularization procedure in the six months prior to Visit 1.
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).
Participation in another clinical trial or exposure to any investigational agent within 30 days before visit 1.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael H Davidson, MD,FACC
Organizational Affiliation
Radiant Research
Official's Role
Principal Investigator
Facility Information:
Facility Name
Radiant Research, 515 N State St, #2700
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60610
Country
United States
12. IPD Sharing Statement
Links:
URL
http://radiantresearch.com
Description
Radiant has 25 wholly-owned clinical research sites (more than 8,000 clinical trials across 18 therapeutic specialties), participant recruitment services (92% enrollment rate), and a full service CRO (IND, phase 1-4, NDA/CTD)
Learn more about this trial
ABT-335 (Choline Fenofibrate) Reverse Cholesterol Transport (RCT) Study
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