Dyslipidemia, Hypercholesterolemia, Hypertriglyceridemia
Conditions
Keywords
Dyslipidemia, Hypercholesterolemia, Hypertriglyceridemia
Brief summary
The primary purpose of this study is to test the effect and safety of three different doses of ABT-143 compared to simvastatin in subjects with elevated levels of low density lipoprotein cholesterol (bad cholesterol) and triglycerides.
Detailed description
There are 4 treatment groups in the study: ABT-143 capsules 20/135 mg, ABT-143 capsules 10/135 mg, ABT-143 5/135 mg, and simvastatin capsules 40 mg. The primary outcome measure only compares 2 of these groups: ABT-143 capsules 20/135 mg and the simvastatin capsules 40 mg groups, therefore there are only results for these 2 groups and not all 4 groups for this outcome measure . Secondary outcome measure (mean percent change in LDL-C comparing ABT-143 capsules 10/135 mg to simvastatin capsules 40 mg) only compares these 2 groups: ABT-143 capsules 10/135 mg and simvastatin capsules 40 mg, therefore there are only results for these 2 groups and not all 4 groups for this outcome measure. Secondary outcome measure (mean percent change in LDL-C comparing ABT-143 capsules 5/135 mg to simvastatin capsules 40 mg) only compares these 2 groups: ABT-143 capsules 5/135 mg and simvastatin capsules 40 mg, therefore there are only results for these 2 groups and not all 4 groups for this outcome measure. For the other pre-specified outcome measures, median percent change in triglycerides from baseline to the final visit and mean percent change in HDL-C from baseline to the final visit for the full analysis sets, all 3 ABT-143 capsules 20/135 mg, 10/135 mg, and 5/135 mg groups were compared to the simvastatin capsules 40 mg group, therefore there are results for all 4 treatment groups for these outcome measures.
Interventions
DRUGABT-143
Once daily for 8 weeks
DRUGsimvastatin
Once daily for 8 weeks simvastatin capsules 40 mg
Sponsors
AstraZeneca
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
* Participants with hypercholesterolemia and hypertriglyceridemia. * Participants had the following fasting lipid results following a greater than or equal to 12 hour fasting period (measured at the Screening Visit(s)): * Triglycerides level greater than or equal to 150 milligrams/deciliter (mg/dL) and less than 400 milligrams/deciliter, and * Low-density lipoprotein cholesterol greater than or equal to 160 milligrams/deciliter and less than or equal to 240 milligrams/deciliter.
Exclusion criteria
* Participants with certain chronic or unstable medical conditions. * Participants receiving coumarin anticoagulants, systemic cyclosporins, or certain other medications. * Pregnant or lactating women, or women intending to become pregnant. * Participants with diabetes mellitus that is poorly controlled. * Participant was of Asian ancestry (having Filipino, Chinese, Japanese, Korean, Vietnamese, or Asian-Indian origin).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change From Baseline to the Final Visit in Low-density Lipoprotein Cholesterol (LDL-C) (Full Analysis Set) | Baseline to 8 weeks | The mean percent change from Baseline to the Final Visit in low-density lipoprotein cholesterol, comparing the following two treatment groups: ABT-143 capsules 20/135 milligrams versus simvastatin capsules 40 milligrams for the full analysis set. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change From Baseline to the Final Visit in Low-density Lipoprotein Cholesterol (LDL-C), With ABT-143 Capsules 10/135 Milligrams Versus Simvastatin Capsules 40 Milligrams (Full Analysis Set) | Baseline to 8 weeks | The mean percent change from Baseline to the Final Visit in low-density lipoprotein cholesterol, comparing the following treatment groups, ABT-143 capsules 10/135 milligrams versus simvastatin capsules 40 milligrams for the full analysis set. |
| Mean Percent Change From Baseline to the Final Visit in Low-density Lipoprotein Cholesterol (LDL-C), With ABT-143 Capsules 5/135 Milligrams Versus Simvastatin Capsules 40 Milligrams (Full Analysis Set) | Baseline to 8 weeks | The mean percent change from Baseline to the Final Visit in low-density lipoprotein cholesterol, comparing the following treatment groups, ABT-143 capsules 5/135 milligrams versus simvastatin capsules 40 milligrams for the full analysis set. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Median Percent Change in Triglycerides From Baseline to the Final Visit (Full Analysis Set) | Baseline to 8 weeks | The ABT-143 capsules 20/135 milligram, ABT-143 capsules 10/135 milligram, and ABT-143 capsules 5/135 milligram groups were compared to the simvastatin capsules 40 milligram group for median percent change in triglycerides from Baseline to the Final Visit for the full analysis set. |
| Mean Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to the Final Visit (Full Analysis Set) | Baseline to 8 weeks | The ABT-143 capsules 20/135 milligram, ABT-143 capsules 10/135 milligram, and ABT-143 capsules 5/135 milligram groups were compared to the simvastatin capsules 40 milligram group for mean percent change in high-density lipoprotein cholesterol from Baseline to the Final Visit for the full analysis set. |
Countries
United States
Participant flow
Recruitment details
474 subjects were randomized and treated at 111 sites in the United States between 29 December 2008 and 14 May 2009.
Participants by arm
| Arm | Count |
|---|---|
| Simvastatin Capsules 40 mg Simvastatin capsules 40 mg once daily for 8 weeks | 119 |
| ABT-143 Capsules 5/135 mg ABT-143 capsules 5/135 mg once daily for 8 weeks | 118 |
| ABT-143 Capsules 10/135 mg ABT-143 capsules 10/135 mg once daily for 8 weeks | 119 |
| ABT-143 Capsules 20/135 mg ABT-143 capsules 20/135 mg once daily for 8 weeks | 118 |
| Total | 474 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 7 | 6 | 3 | 4 |
| Overall Study | Lost to Follow-up | 2 | 1 | 1 | 2 |
| Overall Study | randomized in error | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | Total | Simvastatin Capsules 40 mg | ABT-143 Capsules 5/135 mg | ABT-143 Capsules 10/135 mg | ABT-143 Capsules 20/135 mg |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 101 Participants | 27 Participants | 27 Participants | 24 Participants | 23 Participants |
| Age, Categorical Between 18 and 65 years | 373 Participants | 92 Participants | 91 Participants | 95 Participants | 95 Participants |
| Age Continuous | 56.6 years STANDARD_DEVIATION 9.58 | 56.8 years STANDARD_DEVIATION 9.77 | 56.8 years STANDARD_DEVIATION 8.91 | 56.6 years STANDARD_DEVIATION 9.27 | 56.0 years STANDARD_DEVIATION 10.41 |
| Region of Enrollment United States | 474 participants | 119 participants | 118 participants | 119 participants | 118 participants |
| Sex: Female, Male Female | 252 Participants | 71 Participants | 62 Participants | 59 Participants | 60 Participants |
| Sex: Female, Male Male | 222 Participants | 48 Participants | 56 Participants | 60 Participants | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 119 | 13 / 118 | 6 / 119 | 17 / 118 |
| serious Total, serious adverse events | 0 / 119 | 4 / 118 | 1 / 119 | 3 / 118 |
Outcome results
Primary
Mean Percent Change From Baseline to the Final Visit in Low-density Lipoprotein Cholesterol (LDL-C) (Full Analysis Set)
The mean percent change from Baseline to the Final Visit in low-density lipoprotein cholesterol, comparing the following two treatment groups: ABT-143 capsules 20/135 milligrams versus simvastatin capsules 40 milligrams for the full analysis set.
Time frame: Baseline to 8 weeks
Population: Full Analysis Set was used and defined as all randomized participants who had both a baseline value and at least 1 post-baseline value for LDL-C. Last observation carried forward (LOCF) was used to impute values for participants missing a post-baseline visit value. Only post-baseline values were carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Simvastatin Capsules 40 mg | Mean Percent Change From Baseline to the Final Visit in Low-density Lipoprotein Cholesterol (LDL-C) (Full Analysis Set) | -32.8 percent change | Standard Error 1.59 |
| ABT-143 Capsules 20/135 mg | Mean Percent Change From Baseline to the Final Visit in Low-density Lipoprotein Cholesterol (LDL-C) (Full Analysis Set) | -47.2 percent change | Standard Error 1.6 |
Secondary
Mean Percent Change From Baseline to the Final Visit in Low-density Lipoprotein Cholesterol (LDL-C), With ABT-143 Capsules 10/135 Milligrams Versus Simvastatin Capsules 40 Milligrams (Full Analysis Set)
The mean percent change from Baseline to the Final Visit in low-density lipoprotein cholesterol, comparing the following treatment groups, ABT-143 capsules 10/135 milligrams versus simvastatin capsules 40 milligrams for the full analysis set.
Time frame: Baseline to 8 weeks
Population: Full Analysis Set was used and defined as all randomized participants who had both a baseline value and at least 1 post-baseline value for LDL-C. Last observation carried forward (LOCF) was used to impute values for participants missing a post-baseline visit value. Only post-baseline values were carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Simvastatin Capsules 40 mg | Mean Percent Change From Baseline to the Final Visit in Low-density Lipoprotein Cholesterol (LDL-C), With ABT-143 Capsules 10/135 Milligrams Versus Simvastatin Capsules 40 Milligrams (Full Analysis Set) | -32.8 percent change | Standard Error 1.59 |
| ABT-143 Capsules 20/135 mg | Mean Percent Change From Baseline to the Final Visit in Low-density Lipoprotein Cholesterol (LDL-C), With ABT-143 Capsules 10/135 Milligrams Versus Simvastatin Capsules 40 Milligrams (Full Analysis Set) | -46.0 percent change | Standard Error 1.59 |
Secondary
Mean Percent Change From Baseline to the Final Visit in Low-density Lipoprotein Cholesterol (LDL-C), With ABT-143 Capsules 5/135 Milligrams Versus Simvastatin Capsules 40 Milligrams (Full Analysis Set)
The mean percent change from Baseline to the Final Visit in low-density lipoprotein cholesterol, comparing the following treatment groups, ABT-143 capsules 5/135 milligrams versus simvastatin capsules 40 milligrams for the full analysis set.
Time frame: Baseline to 8 weeks
Population: Full Analysis Set was used and defined as all randomized participants who had both a baseline value and at least 1 post-baseline value for LDL-C. Last observation carried forward (LOCF) was used to impute values for participants missing a post-baseline visit value. Only post-baseline values were carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Simvastatin Capsules 40 mg | Mean Percent Change From Baseline to the Final Visit in Low-density Lipoprotein Cholesterol (LDL-C), With ABT-143 Capsules 5/135 Milligrams Versus Simvastatin Capsules 40 Milligrams (Full Analysis Set) | -32.8 percent change | Standard Error 1.59 |
| ABT-143 Capsules 20/135 mg | Mean Percent Change From Baseline to the Final Visit in Low-density Lipoprotein Cholesterol (LDL-C), With ABT-143 Capsules 5/135 Milligrams Versus Simvastatin Capsules 40 Milligrams (Full Analysis Set) | -38.9 percent change | Standard Error 1.59 |
Other Pre-specified
Mean Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to the Final Visit (Full Analysis Set)
The ABT-143 capsules 20/135 milligram, ABT-143 capsules 10/135 milligram, and ABT-143 capsules 5/135 milligram groups were compared to the simvastatin capsules 40 milligram group for mean percent change in high-density lipoprotein cholesterol from Baseline to the Final Visit for the full analysis set.
Time frame: Baseline to 8 weeks
Population: Full Analysis Set was used and defined as all randomized participants who had both a baseline value and at least 1 post-baseline value for HDL-C. Last observation carried forward (LOCF) was used to impute values for participants missing a post-baseline visit value. Only post-baseline values were carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Simvastatin Capsules 40 mg | Mean Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to the Final Visit (Full Analysis Set) | 9.6 percent change | Standard Error 1.56 |
| ABT-143 Capsules 20/135 mg | Mean Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to the Final Visit (Full Analysis Set) | 16.2 percent change | Standard Error 1.56 |
| ABT-143 Capsules 10/135 mg | Mean Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to the Final Visit (Full Analysis Set) | 14.0 percent change | Standard Error 1.55 |
| ABT-143 Capsules 20/135 mg | Mean Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to the Final Visit (Full Analysis Set) | 15.7 percent change | Standard Error 1.56 |
Other Pre-specified
Median Percent Change in Triglycerides From Baseline to the Final Visit (Full Analysis Set)
The ABT-143 capsules 20/135 milligram, ABT-143 capsules 10/135 milligram, and ABT-143 capsules 5/135 milligram groups were compared to the simvastatin capsules 40 milligram group for median percent change in triglycerides from Baseline to the Final Visit for the full analysis set.
Time frame: Baseline to 8 weeks
Population: Full Analysis Set was used and defined as all randomized participants who had both a baseline value and at least 1 post-baseline value for triglycerides. Last observation carried forward (LOCF) was used to impute values for participants missing a post-baseline visit value. Only post-baseline values were carried forward.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Simvastatin Capsules 40 mg | Median Percent Change in Triglycerides From Baseline to the Final Visit (Full Analysis Set) | -20.8 percent change |
| ABT-143 Capsules 20/135 mg | Median Percent Change in Triglycerides From Baseline to the Final Visit (Full Analysis Set) | -42.7 percent change |
| ABT-143 Capsules 10/135 mg | Median Percent Change in Triglycerides From Baseline to the Final Visit (Full Analysis Set) | -44.6 percent change |
| ABT-143 Capsules 20/135 mg | Median Percent Change in Triglycerides From Baseline to the Final Visit (Full Analysis Set) | -50.0 percent change |