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The objectives of the study are:
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Abt-335 | Experimental | ABT-335 (choline fenofibrate) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| choline fenofibrate | Drug | 135 mg choline fenofibrate daily(oral, capsule) |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) | baseline to 12 weeks |
| Mean Change in Plasma Triglycerides | Change in plasma triglyceride, baseline (average Day 0, 1 10) to end-of-treatment (12 weeks treatment,Day 95) | baseline to 12 weeks |
| 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) | Baseline to 12 weeks |
| Total Cholesterol | Mean Change in total cholesterol from baseline to End-of-treatment (Day 95) | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael H Davidson, MD,FACC | Radiant Research | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Radiant Research, 515 N State St, #2700 | Chicago | Illinois | 60610 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | ABT 335 | choline fenofibrate, 135 mg/day,orally, 12 weeks |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | ABT 335 | choline fenofibrate, 135 mg/day,orally, 12 weeks |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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) | Posted | Mean | Standard Deviation | mg/dL | baseline to 12 weeks |
|
|
12 weeks
All adverse events occurring during the study are reported - the study included a treatment period, with pre-study baseline and post-study end-of-treatment procedures.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ABT 335 | choline fenofibrate, 135 mg/day,orally, 12 weeks |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| diarrhoea | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Michael H. Davidson, MD FACC | Radiant Research | 312-494-2220 | 2220 | michaeldavidson@radiantresearch.com |
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| ID | Term |
|---|---|
| D050171 | Dyslipidemias |
| ID | Term |
|---|---|
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C533234 | 2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropanoic acid |
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| 12 weeks |
| Change in Plasma Cholesterol Ester Fractional Catabolic Rate (FCR) | Change in FCR from baseline to end-of-treatment (12 weeks) | Baseline to 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. | Baseline to 12 weeks |
| 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. | baseline to 12 weeks |
| Change in Bile Acid Excretion | Change in bile acid excretion from baseline to end-of-treatment | Baseline to 12 weeks |
| Neutral Sterol Endogenous Excretion | Change in neutral sterol endogenous excretion from baseline to end-of-treatment | 12 weeks |
| Endogenous Bile Acid Excretion | Change in endogenous bile acid excretion from baseline to end-of-treatment | 12 weeks |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Total cholesterol (TC) | Mean of fasting (> 12 hours) total cholesterol measured at screening, Day 0, 1PM and Day 1, 1AM (Visit 1),Day 10 (Visit 4);23 values, per protocol population | Mean | Standard Deviation | mg/dL |
|
| Triglycerides (TG) | Mean fasting (> 12 hours) triglycerides measured at screening, Day 0, 1PM and Day 1, 1AM (Visit 1), Day 10 (Visit 4);23 values, per protocol population | Mean | Standard Deviation | mg/dL |
|
| High Density Lipoprotein Cholesterol (HDL) | Mean fasting (> 12 hours) HDL cholesterol measured at screening, Day 0, 1PM and Day 1, 1AM (Visit 1), Day 10 (Visit 4); 23 values, per protocol population | Mean | Standard Deviation | mg/dL |
|
| Low density lipoprotein cholesterol (LDL) | Mean fasting (> 12 hours) LDL cholesterol measured at screening, Day 0, 1PM and Day 1, 1AM (Visit 1), Day 10 (Visit 4); 23 values, per protocol population | Mean | Standard Deviation | mg/dL |
|
|
|
| Primary | Mean Change in Plasma Triglycerides | Change in plasma triglyceride, baseline (average Day 0, 1 10) to end-of-treatment (12 weeks treatment,Day 95) | per protocol | Posted | Mean | Standard Deviation | mg/dL | baseline to 12 weeks |
|
|
|
|
| Primary | 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) | Posted | Mean | Standard Deviation | mg/dL | Baseline to 12 weeks |
|
|
|
|
| Secondary | 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. | Not Posted | Mean | Full Range | mg/kg/hr | 12 weeks |
| Secondary | Change in Plasma Cholesterol Ester Fractional Catabolic Rate (FCR) | Change in FCR from baseline to end-of-treatment (12 weeks) | Not Posted | Number | mg/kg/day | Baseline to 12 weeks |
| Secondary | 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. | Not Posted | Number | change, percent | Baseline to 12 weeks |
| Secondary | 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. | Not Posted | Number | Change, mg/day | baseline to 12 weeks |
| Secondary | Change in Bile Acid Excretion | Change in bile acid excretion from baseline to end-of-treatment | Not Posted | Number | percent change | Baseline to 12 weeks |
| Secondary | Neutral Sterol Endogenous Excretion | Change in neutral sterol endogenous excretion from baseline to end-of-treatment | Not Posted | Number | percent | 12 weeks |
| Secondary | Endogenous Bile Acid Excretion | Change in endogenous bile acid excretion from baseline to end-of-treatment | Not Posted | Number | percent | 12 weeks |
| Primary | Total Cholesterol | Mean Change in total cholesterol from baseline to End-of-treatment (Day 95) | Posted | Mean | Standard Deviation | mg/dL | 12 weeks |
|
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|
|
| 0 |
| 25 |
| 14 |
| 25 |
| Dyspepsia | Gastrointestinal disorders | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | Systematic Assessment |
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| back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
|
| rhinorrhea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
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