Dyslipidemia, Coronary Heart Disease, Mixed Dyslipidemia
Conditions
Keywords
Dyslipidemia, Coronary Heart Disease, Mixed Dyslipidemia
Brief summary
The purpose of this study is to compare the safety and efficacy of fenofibric acid (ABT-335) + simvastatin combination therapy with ABT-335 and simvastatin monotherapy in subjects with multiple abnormal lipid levels in the blood.
Interventions
DRUGABT-335
135 mg, daily, 12 weeks
DRUGSimvastatin
daily, 12 weeks, see Arm Description for dosage information
DRUGPlacebo
Daily, 12 weeks, see Arm Description for placebo information
Sponsors
Abbott
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with mixed dyslipidemia * Subjects agree to utilize adequate birth control methods and to adhere to the American Heart Association (AHA) diet.
Exclusion criteria
* Subjects with unstable medical conditions or medical conditions considered inappropriate in a clinical trial. * Patients who are taking certain medications or unstable dose of specific medications. * Women who are pregnant or plan on becoming pregnant, or women who are lactating.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change in Triglycerides From Baseline to Final Visit | Baseline to 12 Weeks (Final Visit) | \[(Week 12 triglycerides minus baseline triglycerides)/baseline triglycerides\] x 100 |
| Mean Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Final Visit | Baseline to 12 Weeks (Final Visit) | \[(Week 12 HDL-C minus baseline HDL-C)/baseline HDL-C\] x 100 |
| Mean Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Final Visit | Baseline to 12 Weeks (Final Visit) | \[(Week 12 LDL-C minus baseline LDL-C)/baseline LDL-C\] x 100 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change in Lipoprotein Apo B (Apo B) From Baseline to Final Visit | Baseline to 12 Weeks (Final Visit) | \[(Week 12 Apo B minus baseline Apo B)/baseline Apo B\] x 100 |
| Mean Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Final Visit | Baseline to 12 Weeks (Final Visit) | \[(Week 12 non-HDL-C minus baseline non-HDL-C)/baseline non-HDL-C\] x 100 |
| Median Percent Change in High-sensitivity C-reactive Protein (hsCRP) From Baseline to Final Visit | Baseline to 12 Weeks (Final Visit) | \[(Week 12 hsCRP minus baseline hsCRP)/baseline hsCRP\] x 100 |
| Mean Percent Change in Very Low-density Lipoprotein Cholesterol (VLDL-C)From Baseline to Final Visit | Baseline to 12 Weeks (Final Visit) | \[(Week 12 VLDL-C minus baseline VLDL-C)/baseline VLDL-C\] x 100 |
| Mean Percent Change in Total Cholesterol From Baseline to Final Visit | Baseline to 12 Weeks (Final Visit) | \[(Week 12 total cholesterol minus baseline total cholesterol)/baseline total cholesterol\] x 100 |
Countries
United States
Participant flow
Pre-assignment details
Seven subjects were randomized but never treated: 2 were taking a prohibited concomitant medication, 1 did not meet the entry criteria for lipid levels, 1 had an abnormal baseline electrocardiogram, 1 was unable to swallow pills, and 2 withdrew consent.
Participants by arm
| Arm | Count |
|---|---|
| ABT-335 + 20 mg Simvastatin ABT-335 + 20 mg simvastatin combination therapy once daily | 119 |
| ABT-335 + 40 mg Simvastatin ABT-335 + 40 mg simvastatin combination therapy once daily | 118 |
| ABT-335 ABT-335 monotherapy once daily | 119 |
| 20 mg Simvastatin 20 mg simvastatin monotherapy once daily | 119 |
| 40 mg Simvastatin 40 mg simvastatin monotherapy once daily | 116 |
| 80 mg Simvastatin 80 mg simvastatin monotherapy once daily | 59 |
| Total | 650 |
Baseline characteristics
| Characteristic | ABT-335 + 20 mg Simvastatin | ABT-335 + 40 mg Simvastatin | ABT-335 | 20 mg Simvastatin | 40 mg Simvastatin | 80 mg Simvastatin | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 18 Participants | 22 Participants | 21 Participants | 15 Participants | 12 Participants | 11 Participants | 99 Participants |
| Age, Categorical Between 18 and 65 years | 101 Participants | 96 Participants | 98 Participants | 104 Participants | 104 Participants | 48 Participants | 551 Participants |
| Region of Enrollment North America | 119 participants | 118 participants | 119 participants | 119 participants | 116 participants | 59 participants | 650 participants |
| Sex: Female, Male Female | 59 Participants | 57 Participants | 68 Participants | 56 Participants | 61 Participants | 31 Participants | 332 Participants |
| Sex: Female, Male Male | 60 Participants | 61 Participants | 51 Participants | 63 Participants | 55 Participants | 28 Participants | 318 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 65 / — | 72 / — | 67 / — | 60 / — | 65 / — | 26 / — |
| serious Total, serious adverse events | 1 / — | 3 / — | 6 / — | 1 / — | 1 / — | 2 / — |
Outcome results
Primary
Mean Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Final Visit
\[(Week 12 HDL-C minus baseline HDL-C)/baseline HDL-C\] x 100
Time frame: Baseline to 12 Weeks (Final Visit)
Population: All randomized subjects with a baseline HDL-C value and at least 1 postbaseline HDL-C value, last observation carried forward
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-335 + 20 mg Simvastatin | Mean Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Final Visit | 17.8 percent change | Standard Error 1.86 |
| ABT-335 + 40 mg Simvastatin | Mean Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Final Visit | 18.9 percent change | Standard Error 1.86 |
| ABT-335 | Mean Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Final Visit | 16.2 percent change | Standard Error 1.85 |
| 20 mg Simvastatin | Mean Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Final Visit | 7.2 percent change | Standard Error 1.8 |
| 40 mg Simvastatin | Mean Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Final Visit | 8.5 percent change | Standard Error 1.89 |
| 80 mg Simvastatin | Mean Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Final Visit | 6.8 percent change | Standard Error 2.61 |
Comparison: An n = 92 per arm would provide 98% power to detect a 9% increase in HDL-C relative to statin monotherapy for each combo therapy dose, assuming an SD of 15%p-value: <0.001ANCOVA
Comparison: An n = 92 per arm would provide 98% power to detect a 9% increase in HDL-C relative to statin monotherapy for each combo therapy dose, assuming an SD of 15%p-value: <0.001ANCOVA
Primary
Mean Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Final Visit
\[(Week 12 LDL-C minus baseline LDL-C)/baseline LDL-C\] x 100
Time frame: Baseline to 12 Weeks (Final Visit)
Population: All randomized subjects with a baseline LDL-C value and at least 1 postbaseline LDL-C value, last observation carried forward
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-335 + 20 mg Simvastatin | Mean Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Final Visit | -24.0 percent change | Standard Error 1.94 |
| ABT-335 + 40 mg Simvastatin | Mean Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Final Visit | -25.3 percent change | Standard Error 1.96 |
| ABT-335 | Mean Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Final Visit | -4.0 percent change | Standard Error 1.96 |
| 20 mg Simvastatin | Mean Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Final Visit | -22.4 percent change | Standard Error 1.9 |
| 40 mg Simvastatin | Mean Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Final Visit | -31.7 percent change | Standard Error 1.98 |
| 80 mg Simvastatin | Mean Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Final Visit | -40.8 percent change | Standard Error 2.69 |
Comparison: An n = 92 per arm would provide \>99% power to detect an 11% decrease in LDL-C relative to ABT-335 monotherapy for each combo therapy dose, assuming an SD of 15%p-value: <0.001ANCOVA
Comparison: An n = 92 per arm would provide \>99% power to detect an 11% decrease in LDL-C relative to ABT-335 monotherapy for each combo therapy dose, assuming an SD of 15%p-value: <0.001ANCOVA
Primary
Mean Percent Change in Triglycerides From Baseline to Final Visit
\[(Week 12 triglycerides minus baseline triglycerides)/baseline triglycerides\] x 100
Time frame: Baseline to 12 Weeks (Final Visit)
Population: All randomized subjects with a baseline triglyceride value and at least 1 postbaseline triglyceride value, last observation carried forward
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-335 + 20 mg Simvastatin | Mean Percent Change in Triglycerides From Baseline to Final Visit | -37.4 percent change | Standard Error 2.75 |
| ABT-335 + 40 mg Simvastatin | Mean Percent Change in Triglycerides From Baseline to Final Visit | -42.7 percent change | Standard Error 2.77 |
| ABT-335 | Mean Percent Change in Triglycerides From Baseline to Final Visit | -31.7 percent change | Standard Error 2.74 |
| 20 mg Simvastatin | Mean Percent Change in Triglycerides From Baseline to Final Visit | -14.2 percent change | Standard Error 2.71 |
| 40 mg Simvastatin | Mean Percent Change in Triglycerides From Baseline to Final Visit | -22.4 percent change | Standard Error 2.76 |
| 80 mg Simvastatin | Mean Percent Change in Triglycerides From Baseline to Final Visit | -20.2 percent change | Standard Error 3.82 |
Comparison: An n = 92 per arm would provide \>99% power to detect a 24% decrease in triglycerides relative to statin monotherapy for each combo therapy dose, assuming an SD of 30%p-value: <0.001ANCOVA
Comparison: An n = 92 per arm would provide \>99% power to detect 24% decrease in triglycerides relative to statin monotherapy for each combo therapy dose, assuming an SD of 30%p-value: <0.001ANCOVA
Secondary
Mean Percent Change in Lipoprotein Apo B (Apo B) From Baseline to Final Visit
\[(Week 12 Apo B minus baseline Apo B)/baseline Apo B\] x 100
Time frame: Baseline to 12 Weeks (Final Visit)
Population: All randomized subjects with a baseline ApoB value and at least 1 postbaseline ApoB value, LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-335 + 20 mg Simvastatin | Mean Percent Change in Lipoprotein Apo B (Apo B) From Baseline to Final Visit | -29.5 percent change | Standard Error 1.47 |
| ABT-335 + 40 mg Simvastatin | Mean Percent Change in Lipoprotein Apo B (Apo B) From Baseline to Final Visit | -31.2 percent change | Standard Error 1.47 |
| ABT-335 | Mean Percent Change in Lipoprotein Apo B (Apo B) From Baseline to Final Visit | -17.6 percent change | Standard Error 1.45 |
| 20 mg Simvastatin | Mean Percent Change in Lipoprotein Apo B (Apo B) From Baseline to Final Visit | -22.9 percent change | Standard Error 1.45 |
| 40 mg Simvastatin | Mean Percent Change in Lipoprotein Apo B (Apo B) From Baseline to Final Visit | -32.7 percent change | Standard Error 1.46 |
| 80 mg Simvastatin | Mean Percent Change in Lipoprotein Apo B (Apo B) From Baseline to Final Visit | -38.9 percent change | Standard Error 2.05 |
Secondary
Mean Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Final Visit
\[(Week 12 non-HDL-C minus baseline non-HDL-C)/baseline non-HDL-C\] x 100
Time frame: Baseline to 12 Weeks (Final Visit)
Population: All randomized subjects with a baseline non-HDL-C value and at least 1 postbaseline non-HDL-C value, LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-335 + 20 mg Simvastatin | Mean Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Final Visit | -30.7 percent change | Standard Error 1.48 |
| ABT-335 + 40 mg Simvastatin | Mean Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Final Visit | -35.0 percent change | Standard Error 1.48 |
| ABT-335 | Mean Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Final Visit | -17.3 percent change | Standard Error 1.46 |
| 20 mg Simvastatin | Mean Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Final Visit | -24.4 percent change | Standard Error 1.43 |
| 40 mg Simvastatin | Mean Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Final Visit | -35.9 percent change | Standard Error 1.49 |
| 80 mg Simvastatin | Mean Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Final Visit | -40.6 percent change | Standard Error 2.06 |
Secondary
Mean Percent Change in Total Cholesterol From Baseline to Final Visit
\[(Week 12 total cholesterol minus baseline total cholesterol)/baseline total cholesterol\] x 100
Time frame: Baseline to 12 Weeks (Final Visit)
Population: All randomized subjects with a baseline total cholesterol value and at least 1 postbaseline total cholesterol value, LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-335 + 20 mg Simvastatin | Mean Percent Change in Total Cholesterol From Baseline to Final Visit | -23.9 percent change | Standard Error 1.2 |
| ABT-335 + 40 mg Simvastatin | Mean Percent Change in Total Cholesterol From Baseline to Final Visit | -27.1 percent change | Standard Error 1.21 |
| ABT-335 | Mean Percent Change in Total Cholesterol From Baseline to Final Visit | -12.4 percent change | Standard Error 1.2 |
| 20 mg Simvastatin | Mean Percent Change in Total Cholesterol From Baseline to Final Visit | -19.8 percent change | Standard Error 1.19 |
| 40 mg Simvastatin | Mean Percent Change in Total Cholesterol From Baseline to Final Visit | -30.0 percent change | Standard Error 1.21 |
| 80 mg Simvastatin | Mean Percent Change in Total Cholesterol From Baseline to Final Visit | -33.6 percent change | Standard Error 1.67 |
Secondary
Mean Percent Change in Very Low-density Lipoprotein Cholesterol (VLDL-C)From Baseline to Final Visit
\[(Week 12 VLDL-C minus baseline VLDL-C)/baseline VLDL-C\] x 100
Time frame: Baseline to 12 Weeks (Final Visit)
Population: All randomized subjects with a baseline VLDL-C value and at least 1 postbaseline VLDL-C value, LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-335 + 20 mg Simvastatin | Mean Percent Change in Very Low-density Lipoprotein Cholesterol (VLDL-C)From Baseline to Final Visit | -38.9 percent change | Standard Error 4.06 |
| ABT-335 + 40 mg Simvastatin | Mean Percent Change in Very Low-density Lipoprotein Cholesterol (VLDL-C)From Baseline to Final Visit | -51.1 percent change | Standard Error 4.03 |
| ABT-335 | Mean Percent Change in Very Low-density Lipoprotein Cholesterol (VLDL-C)From Baseline to Final Visit | -36.9 percent change | Standard Error 4.04 |
| 20 mg Simvastatin | Mean Percent Change in Very Low-density Lipoprotein Cholesterol (VLDL-C)From Baseline to Final Visit | -19.2 percent change | Standard Error 4.04 |
| 40 mg Simvastatin | Mean Percent Change in Very Low-density Lipoprotein Cholesterol (VLDL-C)From Baseline to Final Visit | -35.7 percent change | Standard Error 4.06 |
| 80 mg Simvastatin | Mean Percent Change in Very Low-density Lipoprotein Cholesterol (VLDL-C)From Baseline to Final Visit | -30.0 percent change | Standard Error 5.66 |
Secondary
Median Percent Change in High-sensitivity C-reactive Protein (hsCRP) From Baseline to Final Visit
\[(Week 12 hsCRP minus baseline hsCRP)/baseline hsCRP\] x 100
Time frame: Baseline to 12 Weeks (Final Visit)
Population: All randomized subjects with a baseline hsCRP value and at least 1 postbaseline hsCRP value, LOCF
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| ABT-335 + 20 mg Simvastatin | Median Percent Change in High-sensitivity C-reactive Protein (hsCRP) From Baseline to Final Visit | -26.8 percent change | Inter-Quartile Range 48.27 |
| ABT-335 + 40 mg Simvastatin | Median Percent Change in High-sensitivity C-reactive Protein (hsCRP) From Baseline to Final Visit | -32.1 percent change | Inter-Quartile Range 48.7 |
| ABT-335 | Median Percent Change in High-sensitivity C-reactive Protein (hsCRP) From Baseline to Final Visit | -15.8 percent change | Inter-Quartile Range 48.01 |
| 20 mg Simvastatin | Median Percent Change in High-sensitivity C-reactive Protein (hsCRP) From Baseline to Final Visit | -11.4 percent change | Inter-Quartile Range 48.18 |
| 40 mg Simvastatin | Median Percent Change in High-sensitivity C-reactive Protein (hsCRP) From Baseline to Final Visit | -14.8 percent change | Inter-Quartile Range 48.25 |
| 80 mg Simvastatin | Median Percent Change in High-sensitivity C-reactive Protein (hsCRP) From Baseline to Final Visit | -19.8 percent change | Inter-Quartile Range 67.84 |