Dyslipidemia, Coronary Heart Disease, Mixed Dyslipidemia
Conditions
Brief summary
The primary purpose of this study is to test the safety and the effects of using an investigational drug regimen; once daily ABT-335 (Investigational drug) administered in combination with once daily atorvastatin calcium, rosuvastatin calcium or simvastatin in patients with abnormal lipid levels in the blood.
Interventions
ABT-335 135 mg plus rosuvastatin calcium daily, 52 weeks
DRUGABT-335 and atorvastatin calcium
ABT-335 135 mg plus atorvastatin calcium daily, 52 weeks
DRUGABT-335 and simvastatin
ABT-335 135 mg plus simvastatin daily, 52 weeks
Sponsors
Abbott
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult male and female subjects who voluntarily sign the informed consent. * Subject has successfully completed one of the three ABT-335, rosuvastatin, simvastatin and atorvastatin combination therapy studies.
Exclusion criteria
* Subject is using or will use investigational medications, except as approved by Abbott. * Subject has prematurely discontinued his/her initial therapy one of the prior ABT-335, rosuvastatin, simvastatin and atorvastatin calcium combination therapy studies.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Subjects Reporting Adverse Events During Combination Therapy, Either in the Preceding Double-blind Studies or in This Open-label Study | Anytime after initiation of combination therapy (either in the double-blind or open-label study) to within 30 days after the last dose of combination therapy |
Secondary
| Measure | Time frame |
|---|---|
| Mean Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52 of the Open-label Study | Baseline to Week 52 of the open-label study |
| Mean Percent Change in Direct Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 52 of the Open-label Study | Baseline to Week 52 of the open-label study |
| Mean Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 52 in This Open-label Study | Baseline to Week 52 in this open-label study |
| Median Percent Change in Triglycerides From Baseline to Week 52 of the Open-label Study | Baseline to Week 52 of the open-label study |
| Mean Percent Change in Total Cholesterol From Baseline to Week 52 of the Open-label Study | Baseline to Week 52 of the open-label study |
| Mean Percent Change in Apolipoprotein B (Apo B) From Baseline to Week 52 of the Open-label Study | Baseline to Week 52 of the open-label study |
| Median Percent Change in High-sensitivity C-reactive Protein (hsCRP) From Baseline to Week 52 of the Open-label Study | Baseline to Week 52 of the open-label study |
| Mean Percent Change in Very Low-density Lipoprotein Cholesterol (VLDL-C) From Baseline to Week 52 of the Open-label Study | Baseline to Week 52 of the open-label study |
Countries
United States
Participant flow
Pre-assignment details
1895 subjects were treated in this study. 306 others who did not enroll in this study but were treated with combo therapy in preceding double-blind studies are included in analyses of adverse events. Six subjects were enrolled, but never received study drug. An additional 10 subjects from a site that was closed were not included in any analysis.
Participants by arm
| Arm | Count |
|---|---|
| ABT-335 + 20 mg Rosuvastatin ABT-335 and 20 mg rosuvastatin combination therapy | 1,186 |
| ABT-335 + 40 mg Simvastatin ABT-335 and 40 mg simvastatin combination therapy | 514 |
| ABT-335 + 40 mg Atorvastatin ABT-335 and 40 mg atorvastatin combination therapy | 501 |
| Total | 2,201 |
Baseline characteristics
| Characteristic | ABT-335 + 40 mg Simvastatin | ABT-335 + 40 mg Atorvastatin | ABT-335 + 20 mg Rosuvastatin | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 74 Participants | 103 Participants | 221 Participants | 398 Participants |
| Age, Categorical Between 18 and 65 years | 440 Participants | 397 Participants | 965 Participants | 1802 Participants |
| Age Continuous | 54.1 years STANDARD_DEVIATION 10.25 | 55.5 years STANDARD_DEVIATION 10.86 | 55.1 years STANDARD_DEVIATION 10.79 | 55.0 years STANDARD_DEVIATION 10.69 |
| Region of Enrollment North America | 514 participants | 501 participants | 1186 participants | 2201 participants |
| Sex: Female, Male Female | 256 Participants | 256 Participants | 608 Participants | 1120 Participants |
| Sex: Female, Male Male | 258 Participants | 245 Participants | 578 Participants | 1081 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 646 / — | 308 / — | 283 / — |
| serious Total, serious adverse events | 85 / — | 40 / — | 23 / — |
Outcome results
Primary
Percentage of Subjects Reporting Adverse Events During Combination Therapy, Either in the Preceding Double-blind Studies or in This Open-label Study
Time frame: Anytime after initiation of combination therapy (either in the double-blind or open-label study) to within 30 days after the last dose of combination therapy
Population: Subjects who took at least 1 dose of ABT-335 plus a statin in the preceding double-blind studies or in this open-label study. All adverse events in the preceding studies or in this study occurring with exposure to combination therapy are summarized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-335 + 20 mg Rosuvastatin | Percentage of Subjects Reporting Adverse Events During Combination Therapy, Either in the Preceding Double-blind Studies or in This Open-label Study | 83 percentage of participants |
| ABT-335 + 40 mg Simvastatin | Percentage of Subjects Reporting Adverse Events During Combination Therapy, Either in the Preceding Double-blind Studies or in This Open-label Study | 86 percentage of participants |
| ABT-335 + 40 mg Atorvastatin | Percentage of Subjects Reporting Adverse Events During Combination Therapy, Either in the Preceding Double-blind Studies or in This Open-label Study | 85 percentage of participants |
Secondary
Mean Percent Change in Apolipoprotein B (Apo B) From Baseline to Week 52 of the Open-label Study
Time frame: Baseline to Week 52 of the open-label study
Population: Subjects who took at least 1 dose of ABT-335 plus a statin in the preceding double-blind studies. Baseline is the last value before the first dose of combination therapy in the preceding studies. Percent changes from baseline to Week 52 in this open-label study are summarized. No imputations were made for missing values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-335 + 20 mg Rosuvastatin | Mean Percent Change in Apolipoprotein B (Apo B) From Baseline to Week 52 of the Open-label Study | -44.8 percent change | Standard Deviation 15.4 |
| ABT-335 + 40 mg Simvastatin | Mean Percent Change in Apolipoprotein B (Apo B) From Baseline to Week 52 of the Open-label Study | -35.5 percent change | Standard Deviation 14.85 |
| ABT-335 + 40 mg Atorvastatin | Mean Percent Change in Apolipoprotein B (Apo B) From Baseline to Week 52 of the Open-label Study | -42.9 percent change | Standard Deviation 14.23 |
Secondary
Mean Percent Change in Direct Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 52 of the Open-label Study
Time frame: Baseline to Week 52 of the open-label study
Population: Subjects who took at least 1 dose of ABT-335 plus a statin in the preceding double-blind studies. Baseline is the last value before the first dose of combination therapy in the preceding studies. Percent changes from baseline to Week 52 in this open-label study are summarized. No imputations were made for missing values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-335 + 20 mg Rosuvastatin | Mean Percent Change in Direct Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 52 of the Open-label Study | -41.6 percent change | Standard Deviation 20.77 |
| ABT-335 + 40 mg Simvastatin | Mean Percent Change in Direct Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 52 of the Open-label Study | -30.2 percent change | Standard Deviation 21.83 |
| ABT-335 + 40 mg Atorvastatin | Mean Percent Change in Direct Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 52 of the Open-label Study | -38.1 percent change | Standard Deviation 19.09 |
Secondary
Mean Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52 of the Open-label Study
Time frame: Baseline to Week 52 of the open-label study
Population: Subjects who took at least 1 dose of ABT-335 plus a statin in the preceding double-blind studies. Baseline is the last value before the first dose of combination therapy in the preceding studies. Percent changes from baseline to Week 52 in this open-label study are summarized. No imputations were made for missing values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-335 + 20 mg Rosuvastatin | Mean Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52 of the Open-label Study | 25.2 percent change | Standard Deviation 23.22 |
| ABT-335 + 40 mg Simvastatin | Mean Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52 of the Open-label Study | 25.1 percent change | Standard Deviation 25.08 |
| ABT-335 + 40 mg Atorvastatin | Mean Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52 of the Open-label Study | 19.4 percent change | Standard Deviation 20.58 |
Secondary
Mean Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 52 in This Open-label Study
Time frame: Baseline to Week 52 in this open-label study
Population: Subjects who took at least 1 dose of ABT-335 plus a statin in the preceding double-blind studies. Baseline is the last value before the first dose of combination therapy in the preceding studies. Percent changes from baseline to Week 52 in this open-label study are summarized. No imputations were made for missing values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-335 + 20 mg Rosuvastatin | Mean Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 52 in This Open-label Study | -48.8 percent change | Standard Deviation 15.8 |
| ABT-335 + 40 mg Simvastatin | Mean Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 52 in This Open-label Study | -36.6 percent change | Standard Deviation 16.9 |
| ABT-335 + 40 mg Atorvastatin | Mean Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 52 in This Open-label Study | -44.3 percent change | Standard Deviation 15.72 |
Secondary
Mean Percent Change in Total Cholesterol From Baseline to Week 52 of the Open-label Study
Time frame: Baseline to Week 52 of the open-label study
Population: Subjects who took at least 1 dose of ABT-335 plus a statin in the preceding double-blind studies. Baseline is the last value before the first dose of combination therapy in the preceding studies. Percent changes from baseline to Week 52 in this open-label study are summarized. No imputations were made for missing values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-335 + 20 mg Rosuvastatin | Mean Percent Change in Total Cholesterol From Baseline to Week 52 of the Open-label Study | -37.9 percent change | Standard Deviation 13.14 |
| ABT-335 + 40 mg Simvastatin | Mean Percent Change in Total Cholesterol From Baseline to Week 52 of the Open-label Study | -27.5 percent change | Standard Deviation 14.6 |
| ABT-335 + 40 mg Atorvastatin | Mean Percent Change in Total Cholesterol From Baseline to Week 52 of the Open-label Study | -35.0 percent change | Standard Deviation 13.01 |
Secondary
Mean Percent Change in Very Low-density Lipoprotein Cholesterol (VLDL-C) From Baseline to Week 52 of the Open-label Study
Time frame: Baseline to Week 52 of the open-label study
Population: Subjects who took at least 1 dose of ABT-335 plus a statin in the preceding double-blind studies. Baseline is the last value before the first dose of combination therapy in the preceding studies. Percent changes from baseline to Week 52 in this open-label study are summarized. No imputations were made for missing values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-335 + 20 mg Rosuvastatin | Mean Percent Change in Very Low-density Lipoprotein Cholesterol (VLDL-C) From Baseline to Week 52 of the Open-label Study | -56.9 percent change | Standard Deviation 27.85 |
| ABT-335 + 40 mg Simvastatin | Mean Percent Change in Very Low-density Lipoprotein Cholesterol (VLDL-C) From Baseline to Week 52 of the Open-label Study | -37.7 percent change | Standard Deviation 63.12 |
| ABT-335 + 40 mg Atorvastatin | Mean Percent Change in Very Low-density Lipoprotein Cholesterol (VLDL-C) From Baseline to Week 52 of the Open-label Study | -52.2 percent change | Standard Deviation 36.54 |
Secondary
Median Percent Change in High-sensitivity C-reactive Protein (hsCRP) From Baseline to Week 52 of the Open-label Study
Time frame: Baseline to Week 52 of the open-label study
Population: Subjects who took at least 1 dose of ABT-335 plus a statin in the preceding double-blind studies. Baseline is the last value before the first dose of combination therapy in the preceding studies. Percent changes from baseline to Week 52 in this open-label study are summarized. No imputations were made for missing values.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| ABT-335 + 20 mg Rosuvastatin | Median Percent Change in High-sensitivity C-reactive Protein (hsCRP) From Baseline to Week 52 of the Open-label Study | -38.87 percent change | Full Range 265.37 |
| ABT-335 + 40 mg Simvastatin | Median Percent Change in High-sensitivity C-reactive Protein (hsCRP) From Baseline to Week 52 of the Open-label Study | -27.72 percent change | Full Range 93.62 |
| ABT-335 + 40 mg Atorvastatin | Median Percent Change in High-sensitivity C-reactive Protein (hsCRP) From Baseline to Week 52 of the Open-label Study | -39.13 percent change | Full Range 70.99 |
Secondary
Median Percent Change in Triglycerides From Baseline to Week 52 of the Open-label Study
Time frame: Baseline to Week 52 of the open-label study
Population: Subjects who took at least 1 dose of ABT-335 plus a statin in the preceding double-blind studies. Baseline is the last value before the first dose of combination therapy in the preceding studies. Percent changes from baseline to Week 52 in this open-label study are summarized. No imputations were made for missing values.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| ABT-335 + 20 mg Rosuvastatin | Median Percent Change in Triglycerides From Baseline to Week 52 of the Open-label Study | -53.0 percent change | Full Range 27.67 |
| ABT-335 + 40 mg Simvastatin | Median Percent Change in Triglycerides From Baseline to Week 52 of the Open-label Study | -47.7 percent change | Full Range 24.62 |
| ABT-335 + 40 mg Atorvastatin | Median Percent Change in Triglycerides From Baseline to Week 52 of the Open-label Study | -56.2 percent change | Full Range 24.56 |