Mixed Dyslipidemia
Conditions
Brief summary
The objective of the study is to assess the continued safety of the daily coadministration of ABT-335 in combination with rosuvastatin calcium, simvastatin or atorvastatin calcium.
Interventions
DRUGABT-335
Oral coadministration of ABT-335 (135 mg) once daily, beginning in either the 12-week double-blind study or the previous 52-week open-label year 1 study and continuing in 52-week year 2 study
Oral coadministration of rosuvastatin calcium (20 mg) once daily, beginning in either the 12-week double-blind study or the previous 52-week open-label year 1 study and continuing in 52-week year 2 study
DRUGsimvastatin
Oral coadministration of simvastatin (40 mg) once daily, beginning in either the 12-week double-blind study or the previous 52-week open-label year 1 study and continuing in 52-week year 2 study
DRUGatorvastatin calcium
Oral coadministration of atorvastatin calcium (40 mg) once daily, beginning in either the 12-week double-blind study or the previous 52-week open-label year 1 study and continuing in 52-week year 2 study
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 the treatment phase of the preceding open-label year 1 study.
Exclusion criteria
* Subject is using or will use investigational medications, except as approved by Abbott. * Subject has prematurely discontinued his/her combination therapy administered in the preceding open-label year 1 study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Reporting Adverse Events During Combination Therapy in the Preceding Double-Blind Studies or in the Preceding Open-Label Year 1 Study or in This Open-Label Year 2 Study | Anytime after initiation of combination therapy (in the preceding 12-week double-blind studies or in the preceding open-label year 1 study) up to 116 weeks, to within 30 days after the last dose of combination therapy. | All serious and non-serious adverse events are reported from the time of combination study drug initiation until 30 days after discontinuation of study drug. Adverse events are unfavorable changes in health that occur in subjects during a clinical trial or within a specified period following a trial. Serious adverse events are those that result in death, require inpatient hospitalization or the prolongation of hospitalization, result in congenital anomaly/birth defect, or significant disability/incapacity or are life-threatening. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change in High-Density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 104 of This Open-Label Year 2 Study | Baseline to Week 104 (may include weeks in preceding double-blind studies [combination treatment arms], plus 52 weeks in preceding open-label year 1 study, and open-label year 2 study, up to 104 weeks) | \[(Week 104 HDL-C minus baseline HDL-C)/baseline HDL-C\] X 100. Baseline is the last value prior to the first dose of combination therapy. |
| Mean Percent Change in Direct Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 104 of This Open-Label Year 2 Study | Baseline to Week 104 (may include weeks in preceding double-blind studies [combination treatment arms], plus 52 weeks in preceding open-label year 1 study, and open-label year 2 study, up to 104 weeks) | \[(Week 104 LDL-C minus baseline LDL-C)/baseline LDL-C\] X 100. Baseline is the last value prior to the first dose of combination therapy. |
| Median Percent Change in Triglycerides From Baseline to Week 104 of This Open-Label Year 2 Study | Baseline to Week 104 (may include weeks in preceding double-blind studies [combination treatment arms], plus 52 weeks in preceding open-label year 1 study, and open-label year 2 study, up to 104 weeks) | \[(Week 104 triglycerides minus baseline triglycerides)/baseline triglycerides\] X 100. Baseline is the last value prior to the first dose of combination therapy. |
| Mean Percent Change in Very Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Week 104 of This Open-Label Year 2 Study | Baseline to Week 104 (may include weeks in preceding double-blind studies [combination treatment arms], plus 52 weeks in preceding open-label year 1 study, and open-label year 2 study, up to 104 weeks) | \[(Week 104 VLDL-C minus baseline VLDL-C)/baseline VLDL-C\] X 100. Baseline is the last value prior to the first dose of combination therapy. |
| Mean Percent Change in Total Cholesterol (Total-C) From Baseline to Week 104 of This Open-Label Year 2 Study | Baseline to Week 104 (may include weeks in preceding double-blind studies [combination treatment arms], plus 52 weeks in preceding open-label year 1 study, and open-label year 2 study, up to 104 weeks) | \[(Week 104 Total-C minus baseline Total-C)/baseline Total-C\] X 100. Baseline is the last value prior to the first dose of combination therapy. |
| Mean Percent Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 104 of This Open-Label Year 2 Study | Baseline to Week 104 (may include weeks in preceding double-blind studies [combination treatment arms], plus 52 weeks in preceding open-label year 1 study, and open-label year 2 study, up to 104 weeks) | \[(Week 104 Non-HDL-C minus baseline Non-HDL-C)/baseline Non-HDL-C\] X 100. Baseline is the last value prior to the first dose of combination therapy. |
Countries
United States
Participant flow
Recruitment details
Subjects who had completed ABT-335/statin therapy in the preceding open-label year 1 study at a subset of sites were eligible for recruitment in this open-label year 2 extension study. Subjects continued to receive the treatment they had received in the preceding open-label year 1 study.
Participants by arm
| Arm | Count |
|---|---|
| ABT-335 + 20 mg Rosuvastatin Oral coadministration of ABT-335 (135 mg) + rosuvastatin (20 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study | 174 |
| ABT-335 + 40 mg Simvastatin Oral coadministration of ABT-335 (135 mg) + simvastatin (40 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study | 50 |
| ABT-335 + 40 mg Atorvastatin Oral coadministration of ABT-335 (135 mg) + atorvastatin (40 mg), once daily, for up to 116 weeks (if beginning in the 12-week double-blind study) or up to 104 weeks (if beginning in the previous 52-week open-label year 1 study) and continuing in 52-week year 2 study | 86 |
| Total | 310 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 1 | 2 |
| Overall Study | Investigator Discretion | 0 | 1 | 0 |
| Overall Study | Lack of Efficacy | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 2 | 2 |
| Overall Study | Patient Request | 0 | 1 | 0 |
| Overall Study | Use of Prohibited Medication | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | ABT-335 + 20 mg Rosuvastatin | ABT-335 + 40 mg Simvastatin | ABT-335 + 40 mg Atorvastatin | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 36 Participants | 10 Participants | 18 Participants | 64 Participants |
| Age, Categorical Between 18 and 65 years | 138 Participants | 40 Participants | 68 Participants | 246 Participants |
| Age Continuous | 56.1 years STANDARD_DEVIATION 10.71 | 55.3 years STANDARD_DEVIATION 10.55 | 55.4 years STANDARD_DEVIATION 10.94 | 55.8 years STANDARD_DEVIATION 10.72 |
| Region of Enrollment United States | 174 participants | 50 participants | 86 participants | 310 participants |
| Sex: Female, Male Female | 77 Participants | 29 Participants | 42 Participants | 148 Participants |
| Sex: Female, Male Male | 97 Participants | 21 Participants | 44 Participants | 162 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 | 153 / 174 | 44 / 50 | 81 / 86 |
| serious Total, serious adverse events | 26 / 174 | 4 / 50 | 5 / 86 |
Outcome results
Primary
Percentage of Subjects Reporting Adverse Events During Combination Therapy in the Preceding Double-Blind Studies or in the Preceding Open-Label Year 1 Study or in This Open-Label Year 2 Study
All serious and non-serious adverse events are reported from the time of combination study drug initiation until 30 days after discontinuation of study drug. Adverse events are unfavorable changes in health that occur in subjects during a clinical trial or within a specified period following a trial. Serious adverse events are those that result in death, require inpatient hospitalization or the prolongation of hospitalization, result in congenital anomaly/birth defect, or significant disability/incapacity or are life-threatening.
Time frame: Anytime after initiation of combination therapy (in the preceding 12-week double-blind studies or in the preceding open-label year 1 study) up to 116 weeks, 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 preceding open-label year 1 study, and in this open-label year 2 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 in the Preceding Double-Blind Studies or in the Preceding Open-Label Year 1 Study or in This Open-Label Year 2 Study | 94.8 percentage of participants |
| ABT-335 + 40 mg Simvastatin | Percentage of Subjects Reporting Adverse Events During Combination Therapy in the Preceding Double-Blind Studies or in the Preceding Open-Label Year 1 Study or in This Open-Label Year 2 Study | 90.0 percentage of participants |
| ABT-335 + 40 mg Atorvastatin | Percentage of Subjects Reporting Adverse Events During Combination Therapy in the Preceding Double-Blind Studies or in the Preceding Open-Label Year 1 Study or in This Open-Label Year 2 Study | 97.7 percentage of participants |
Secondary
Mean Percent Change in Direct Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 104 of This Open-Label Year 2 Study
\[(Week 104 LDL-C minus baseline LDL-C)/baseline LDL-C\] X 100. Baseline is the last value prior to the first dose of combination therapy.
Time frame: Baseline to Week 104 (may include weeks in preceding double-blind studies [combination treatment arms], plus 52 weeks in preceding open-label year 1 study, and open-label year 2 study, up to 104 weeks)
Population: Subjects who took at least 1 dose of ABT-335 plus a statin in the preceding double-blind studies or preceding open-label year 1 study, and in this open-label year 2 study. Only subjects with a combination therapy baseline value and postbaseline value at Week 104 are included.
| 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 104 of This Open-Label Year 2 Study | -19.2 percent change | Standard Deviation 30.87 |
| ABT-335 + 40 mg Simvastatin | Mean Percent Change in Direct Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 104 of This Open-Label Year 2 Study | -20.2 percent change | Standard Deviation 22.56 |
| ABT-335 + 40 mg Atorvastatin | Mean Percent Change in Direct Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 104 of This Open-Label Year 2 Study | -20.5 percent change | Standard Deviation 30.04 |
Secondary
Mean Percent Change in High-Density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 104 of This Open-Label Year 2 Study
\[(Week 104 HDL-C minus baseline HDL-C)/baseline HDL-C\] X 100. Baseline is the last value prior to the first dose of combination therapy.
Time frame: Baseline to Week 104 (may include weeks in preceding double-blind studies [combination treatment arms], plus 52 weeks in preceding open-label year 1 study, and open-label year 2 study, up to 104 weeks)
Population: Subjects who took at least 1 dose of ABT-335 plus a statin in the preceding double-blind studies or preceding open-label year 1 study, and in this open-label year 2 study. Only subjects with a combination therapy baseline value and postbaseline value at week 104 are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-335 + 20 mg Rosuvastatin | Mean Percent Change in High-Density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 104 of This Open-Label Year 2 Study | 13.7 percent change | Standard Deviation 22.15 |
| ABT-335 + 40 mg Simvastatin | Mean Percent Change in High-Density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 104 of This Open-Label Year 2 Study | 11.2 percent change | Standard Deviation 22.53 |
| ABT-335 + 40 mg Atorvastatin | Mean Percent Change in High-Density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 104 of This Open-Label Year 2 Study | 5.2 percent change | Standard Deviation 17.53 |
Secondary
Mean Percent Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 104 of This Open-Label Year 2 Study
\[(Week 104 Non-HDL-C minus baseline Non-HDL-C)/baseline Non-HDL-C\] X 100. Baseline is the last value prior to the first dose of combination therapy.
Time frame: Baseline to Week 104 (may include weeks in preceding double-blind studies [combination treatment arms], plus 52 weeks in preceding open-label year 1 study, and open-label year 2 study, up to 104 weeks)
Population: Subjects who took at least 1 dose of ABT-335 plus a statin in the preceding double-blind studies or preceding open-label year 1 study, and in this open-label year 2 study. Only subjects with a combination therapy baseline value and postbaseline value at Week 104 are included.
| 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 104 of This Open-Label Year 2 Study | -26.9 percent change | Standard Deviation 26.12 |
| ABT-335 + 40 mg Simvastatin | Mean Percent Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 104 of This Open-Label Year 2 Study | -23.8 percent change | Standard Deviation 21.99 |
| ABT-335 + 40 mg Atorvastatin | Mean Percent Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 104 of This Open-Label Year 2 Study | -25.1 percent change | Standard Deviation 27.83 |
Secondary
Mean Percent Change in Total Cholesterol (Total-C) From Baseline to Week 104 of This Open-Label Year 2 Study
\[(Week 104 Total-C minus baseline Total-C)/baseline Total-C\] X 100. Baseline is the last value prior to the first dose of combination therapy.
Time frame: Baseline to Week 104 (may include weeks in preceding double-blind studies [combination treatment arms], plus 52 weeks in preceding open-label year 1 study, and open-label year 2 study, up to 104 weeks)
Population: Subjects who took at least 1 dose of ABT-335 plus a statin in the preceding double-blind studies or preceding open-label year 1 study, and in this open-label year 2 study. Only subjects with a combination therapy baseline value and postbaseline value at Week 104 are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-335 + 20 mg Rosuvastatin | Mean Percent Change in Total Cholesterol (Total-C) From Baseline to Week 104 of This Open-Label Year 2 Study | -20.1 percent change | Standard Deviation 21.41 |
| ABT-335 + 40 mg Simvastatin | Mean Percent Change in Total Cholesterol (Total-C) From Baseline to Week 104 of This Open-Label Year 2 Study | -17.9 percent change | Standard Deviation 18.54 |
| ABT-335 + 40 mg Atorvastatin | Mean Percent Change in Total Cholesterol (Total-C) From Baseline to Week 104 of This Open-Label Year 2 Study | -20.4 percent change | Standard Deviation 21.57 |
Secondary
Mean Percent Change in Very Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Week 104 of This Open-Label Year 2 Study
\[(Week 104 VLDL-C minus baseline VLDL-C)/baseline VLDL-C\] X 100. Baseline is the last value prior to the first dose of combination therapy.
Time frame: Baseline to Week 104 (may include weeks in preceding double-blind studies [combination treatment arms], plus 52 weeks in preceding open-label year 1 study, and open-label year 2 study, up to 104 weeks)
Population: Subjects who took at least 1 dose of ABT-335 plus a statin in the preceding double-blind studies or preceding open-label year 1 study, and in this open-label year 2 study. Only subjects with a combination therapy baseline value and postbaseline value at Week 104 are included.
| 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 104 of This Open-Label Year 2 Study | -33.7 percent change | Standard Deviation 42.5 |
| ABT-335 + 40 mg Simvastatin | Mean Percent Change in Very Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Week 104 of This Open-Label Year 2 Study | -18.7 percent change | Standard Deviation 58.37 |
| ABT-335 + 40 mg Atorvastatin | Mean Percent Change in Very Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Week 104 of This Open-Label Year 2 Study | -26.6 percent change | Standard Deviation 65.88 |
Secondary
Median Percent Change in Triglycerides From Baseline to Week 104 of This Open-Label Year 2 Study
\[(Week 104 triglycerides minus baseline triglycerides)/baseline triglycerides\] X 100. Baseline is the last value prior to the first dose of combination therapy.
Time frame: Baseline to Week 104 (may include weeks in preceding double-blind studies [combination treatment arms], plus 52 weeks in preceding open-label year 1 study, and open-label year 2 study, up to 104 weeks)
Population: Subjects who took at least 1 dose of ABT-335 plus a statin in the preceding double-blind studies or preceding open-label year 1 study, and in this open-label year 2 study. Only subjects with a combination therapy baseline value and postbaseline value at Week 104 are included.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| ABT-335 + 20 mg Rosuvastatin | Median Percent Change in Triglycerides From Baseline to Week 104 of This Open-Label Year 2 Study | -36.9 percent change | Full Range 34.91 |
| ABT-335 + 40 mg Simvastatin | Median Percent Change in Triglycerides From Baseline to Week 104 of This Open-Label Year 2 Study | -29.6 percent change | Full Range 36.61 |
| ABT-335 + 40 mg Atorvastatin | Median Percent Change in Triglycerides From Baseline to Week 104 of This Open-Label Year 2 Study | -38.7 percent change | Full Range 32.31 |