Clinical trial NCT00673881: ABT-335 (Choline Fenofibrate) Reverse Cholesterol Transport (RCT) Study
Official title: ABT-335 (Choline Fenofibrate)Reverse Cholesterol Transport (RCT) Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Dyslipidemia
Lead sponsor: Radiant Research
Sponsor class: OTHER
First posted: 2008-05-07
Enrollment: 25
Sex: ALL
Minimum age (years): 21
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Primary outcomes:
measure: Mean Change in Calculated Low Density Lipoprotein Cholesterol
timeFrame: baseline to 12 weeks
measure: Mean Change in Plasma Triglycerides
timeFrame: baseline to 12 weeks
measure: Mean Change in High Density Lipoprotein Cholesterol
timeFrame: Baseline to 12 weeks
measure: Total Cholesterol
timeFrame: 12 weeks
Secondary outcomes:
measure: Plasma Cholesterol Efflux
timeFrame: 12 weeks
measure: Change in Plasma Cholesterol Ester Fractional Catabolic Rate (FCR)
timeFrame: Baseline to 12 weeks
measure: Percent Change in de Novo Cholesterol Synthesis
timeFrame: Baseline to 12 weeks
measure: Change in Neutral Sterol Excretion
timeFrame: baseline to 12 weeks
measure: Change in Bile Acid Excretion
timeFrame: Baseline to 12 weeks
measure: Neutral Sterol Endogenous Excretion
timeFrame: 12 weeks
measure: Endogenous Bile Acid Excretion
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Radiant Research, 515 N State St, #2700
state: Illinois
Study officials:
affiliation: Radiant Research
name: Michael H Davidson, MD,FACC
role: PRINCIPAL_INVESTIGATOR
References: