Coronary Artery Disease, Coronary Heart Disease, Dyslipidemia
Conditions
Brief summary
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.
Interventions
Sponsors
AbbVie (prior sponsor, Abbott)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Change in Mean Posterior-wall Carotid Intima-media Thickness (cIMT) | Baseline, 6 months, 12 months, 18 months, and 24 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Change in Mean of Maximal Posterior-wall Carotid Intima-media Thickness (cIMT) | Baseline, 6 months, 12 months, 18 months, and 24 months | 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. |
| Rate of Change in Composite of Mean of the Mean Posterior-wall Intima-media Thickness (IMT) | Baseline, 6 months, 12 months, 18 months, and 24 months | 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. |
| Rate of Change in Composite of Mean of Maximal Posterior-wall Intima-media Thickness (IMT) | Baseline, 6 months, 12 months, 18 months, and 24 months | 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. |
| Rate of Change in Composite of Mean of Maximal Posterior-wall and Anterior-wall Intima-media Thickness (IMT) | Baseline, 6 months, 12 months, 18 months, and 24 months | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ABT-335 + Atorvastatin ABT-335 (135 mg) and atorvastatin (up to 40 mg) once daily for 2 years. | 337 |
| Placebo + Atorvastatin Placebo and atorvastatin (up to 40 mg) once daily for 2 years. | 339 |
| Total | 676 |
Baseline characteristics
| Characteristic | ABT-335 + Atorvastatin | Placebo + Atorvastatin | Total |
|---|---|---|---|
| Age, Continuous | 60.8 years STANDARD_DEVIATION 8.71 | 60.7 years STANDARD_DEVIATION 8.79 | 60.8 years STANDARD_DEVIATION 8.75 |
| Low-density Lipoprotein Cholesterol (LDL-C) | 84.0 mg/dL STANDARD_DEVIATION 21.3 | 84.5 mg/dL STANDARD_DEVIATION 20.47 | 84.3 mg/dL STANDARD_DEVIATION 20.88 |
| Posterior-wall Carotid Intima-media (cIMT) Thickness | 0.76 mm STANDARD_DEVIATION 0.1 | 0.78 mm STANDARD_DEVIATION 0.12 | 0.77 mm STANDARD_DEVIATION 0.11 |
| Sex: Female, Male Female | 109 Participants | 109 Participants | 218 Participants |
| Sex: Female, Male Male | 228 Participants | 230 Participants | 458 Participants |
| Triglycerides | 226.3 mg/dL STANDARD_DEVIATION 110.01 | 228.7 mg/dL STANDARD_DEVIATION 127.06 | 227.5 mg/dL STANDARD_DEVIATION 118.78 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 235 / 337 | 241 / 339 |
| serious Total, serious adverse events | 58 / 337 | 66 / 339 |
Outcome results
Primary
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.
Time frame: Baseline, 6 months, 12 months, 18 months, and 24 months
Population: All randomized participants who had both a baseline value and at least 1 postbaseline value for that parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-335 + Atorvastatin | Rate of Change in Mean Posterior-wall Carotid Intima-media Thickness (cIMT) | -0.006 mm/year | Standard Error 0.0037 |
| Placebo + Atorvastatin | Rate of Change in Mean Posterior-wall Carotid Intima-media Thickness (cIMT) | 0.000 mm/year | Standard Error 0.0036 |
p-value: 0.2295% CI: [-0.016, 0.004]Repeated measures linear mixed model
Secondary
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.
Time frame: Baseline, 6 months, 12 months, 18 months, and 24 months
Population: All randomized subjects who had both a baseline value and at least 1 postbaseline value for that parameter, as well as 6 or more matching segments at baseline and the 2-year visit. Observations at the interim visits were included only if 6 or more segments matched the segments at baseline and at 2 years.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-335 + Atorvastatin | Rate of Change in Composite of Mean of Maximal Posterior-wall and Anterior-wall Intima-media Thickness (IMT) | -0.003 mm/year | Standard Error 0.007 |
| Placebo + Atorvastatin | Rate of Change in Composite of Mean of Maximal Posterior-wall and Anterior-wall Intima-media Thickness (IMT) | -0.019 mm/year | Standard Error 0.0067 |
p-value: 0.11295% CI: [-0.004, 0.035]Repeated measures linear mixed model
Secondary
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.
Time frame: Baseline, 6 months, 12 months, 18 months, and 24 months
Population: All randomized subjects who had both a baseline value and at least 1 postbaseline value for that parameter, as well as 3 or more matching segments at baseline and the 2-year visit. Observations at the interim visits were included only if 3 or more segments matched the segments at baseline and at 2 years.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-335 + Atorvastatin | Rate of Change in Composite of Mean of Maximal Posterior-wall Intima-media Thickness (IMT) | -0.014 mm/year | Standard Error 0.0053 |
| Placebo + Atorvastatin | Rate of Change in Composite of Mean of Maximal Posterior-wall Intima-media Thickness (IMT) | -0.008 mm/year | Standard Error 0.0056 |
p-value: 0.48795% CI: [-0.02, 0.01]Repeated measures linear mixed model
Secondary
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.
Time frame: Baseline, 6 months, 12 months, 18 months, and 24 months
Population: All randomized subjects who had both a baseline value and at least 1 postbaseline value for that parameter, as well as 3 or more matching segments at baseline and the 2-year visit. Observations at the interim visits were included only if 3 or more segments matched the segments at baseline and at 2 years.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-335 + Atorvastatin | Rate of Change in Composite of Mean of the Mean Posterior-wall Intima-media Thickness (IMT) | -0.010 mm/year | Standard Error 0.0039 |
| Placebo + Atorvastatin | Rate of Change in Composite of Mean of the Mean Posterior-wall Intima-media Thickness (IMT) | -0.004 mm/year | Standard Error 0.0041 |
p-value: 0.24995% CI: [-0.018, 0.005]Repeated measures linear mixed model
Secondary
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.
Time frame: Baseline, 6 months, 12 months, 18 months, and 24 months
Population: All randomized subjects who had both a baseline value and at least 1 postbaseline value for that parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-335 + Atorvastatin | Rate of Change in Mean of Maximal Posterior-wall Carotid Intima-media Thickness (cIMT) | -0.005 mm/year | Standard Error 0.0047 |
| Placebo + Atorvastatin | Rate of Change in Mean of Maximal Posterior-wall Carotid Intima-media Thickness (cIMT) | -0.003 mm/year | Standard Error 0.0046 |
p-value: 0.81395% CI: [-0.014, 0.011]Repeated measures linear mixed model