Safety and Efficacy Study Using ABT-335 (Investigational Drug) in Combination With Atorvastatin, to Study the Effects on Thickening of the Blood Vessel Wall in Patients With Abnormal Lipid (Fat) Levels in the Blood

Study Overview
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Brief Summary
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The primary purpose of this study is to test the effect and safety of once daily ABT-335 on the thickness of the lining of the carotid artery (a blood vessel to the brain) in patients with abnormal blood lipids who have optimal levels of low density lipoprotein cholesterol (bad cholesterol) after taking atorvastatin.

Official Title
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Evaluation of Choline Fenofibrate (ABT-335) on Carotid Intima-Media Thickness (cIMT) in Subjects With Type IIb Dyslipidemia With Residual Risk in Addition to Atorvastatin Therapy (FIRST) Trial

Conditions
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Coronary Artery Disease, Coronary Heart Disease, Dyslipidemia

Intervention / Treatment
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* Drug: ABT-335
* Drug: Placebo
* Other: Atorvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with mixed dyslipidemia Qualifying cIMT thickness Exclusion Criteria: Patients with certain chronic or unstable medical conditions. Patients with unstable dose of medications or receiving coumadin, cyclosporine, or certain other medications Pregnant or lactating women or women intending to become pregnant Patients with diabetes mellitus that is poorly controlled

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABT-335 + Atorvastatin<br>ABT-335 (135 mg) and atorvastatin (up to 40 mg) once daily for 2 years. | Drug: ABT-335<br>* Capsule<br>* Other names: Fenofibric acid;Other: Atorvastatin<br>* Capsule<br>|
| Placebo Comparator: Placebo + Atorvastatin<br>Placebo and atorvastatin (up to 40 mg) once daily for 2 years. | Drug: Placebo<br>* Capsule<br>Other: Atorvastatin<br>* Capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Change in Mean Posterior-wall Carotid Intima-media Thickness (cIMT) | Rate of change (mm/year) from baseline in mean of posterior-wall carotid intima-media thickness (cIMT) of the left and right common carotid artery. The statistical model used change from baseline as the dependent variable, with time of cIMT assessment (in years) as one of the factors in the model. The between-group difference in the rate of change was based on the parameter coefficient for the time-by-treatment interaction. The within-group rate of change was obtained from estimate statements within the repeated measures analysis. cIMT was measured using non-invasive ultrasound. | Baseline, 6 months, 12 months, 18 months, and 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Change in Mean of Maximal Posterior-wall Carotid Intima-media Thickness (cIMT) | Rate of change (mm/year) from baseline in mean of maximal posterior-wall carotid intima-media thickness (cIMT) of the left and right common carotid artery. The statistical model used change from baseline as the dependent variable, with time of cIMT assessment (in years) as one of the factors in the model. The between-group difference in the rate of change was based on the parameter coefficient for the time-by-treatment interaction. The within-group rate of change was obtained from estimate statements within the repeated measures analysis. cIMT was measured using non-invasive ultrasound. | Baseline, 6 months, 12 months, 18 months, and 24 months | 
| Rate of Change in Composite of Mean of the Mean Posterior-wall Intima-media Thickness (IMT) | Rate of change (mm/year) from baseline in composite of mean of the mean posterior-wall intima-media thickness (IMT) of the left and right common carotid artery, internal carotid artery, and carotid bifurcation. The statistical model used change from baseline as the dependent variable, with time of IMT assessment (in years) as one of the factors in the model. The between-group difference in the rate of change was based on the parameter coefficient for the time-by-treatment interaction. The within-group rate of change was obtained from estimate statements within the repeated measures analysis. IMT was measured using non-invasive ultrasound. | Baseline, 6 months, 12 months, 18 months, and 24 months | 
| Rate of Change in Composite of Mean of Maximal Posterior-wall Intima-media Thickness (IMT) | Rate of change (mm/year) from baseline in composite of mean of maximal posterior-wall intima-media thickness (IMT) of the left and right common carotid artery, internal carotid artery, and carotid bifurcation. The statistical model used change from baseline as the dependent variable, with time of IMT assessment (in years) as one of the factors in the model. The between-group difference in the rate of change was based on the parameter coefficient for the time-by-treatment interaction. The within-group rate of change was obtained from estimate statements within the repeated measures analysis. IMT was measured using non-invasive ultrasound. | Baseline, 6 months, 12 months, 18 months, and 24 months | 
| Rate of Change in Composite of Mean of Maximal Posterior-wall and Anterior-wall Intima-media Thickness (IMT) | Rate of change (mm/year) from baseline in composite of mean of maximal posterior-wall and anterior-wall intima-media thickness (IMT) of the left and right common carotid artery, internal carotid artery, and carotid bifurcation. The statistical model used change from baseline as the dependent variable, with time of IMT assessment (in years) as one of the factors in the model. The between-group difference in the rate of change was based on the parameter coefficient for the time-by-treatment interaction. The within-group rate of change was obtained from estimate statements within the repeated measures analysis. IMT was measured using non-invasive ultrasound. | Baseline, 6 months, 12 months, 18 months, and 24 months |