Dyslipidemia, Kidney Disease
Conditions
Keywords
Dyslipidemia, Kidney Disease
Brief summary
The objective of this study is to evaluate the safety and efficacy of the combination of ABT-335 plus rosuvastatin in dyslipidemic subjects with Chronic Kidney Disease (CKD) Stage 3.
Interventions
DRUGABT-335 plus rosuvastatin
ABT-335 45 mg plus rosuvastatin 5 mg for 8 weeks, then ABT-335 45 mg plus rosuvastatin 10 mg for 8 weeks
DRUGRosuvastatin
Rosuvastatin 5 mg for 8 weeks then rosuvastatin 10 mg for 8 weeks
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Dyslipidemic participants with Chronic Kidney Disease Stage 3 * For entry into the Treatment Phase (Visit 3), the participant satisfied the following laboratory criteria (measured at the Screening Visit\[s\]): * Estimated glomerular filtration rate between 30 and 59 mL/min/1.73 m2 (Chronic Kidney Disease Stage 3) by simplified 4 variable Modification of Diet in Renal Disease formula (this includes a 10 percent variation in the upper limit of estimated glomerular filtration rate that was allowed for the enrollment of participants to account for variability in the creatinine assay). * Fasting lipid results following greater than or equal to 12-hour fasting period: * Triglycerides level greater than or equal to 150 mg/dL, * High-density lipoprotein cholesterol less than 40 mg/dL for males and less than 50 mg/dL for females, and * Low-density lipoprotein cholesterol greater than or equal to 130 mg/dL
Exclusion criteria
* Participants with certain chronic or unstable medical conditions. * Participants with unstable dose of medications or receiving coumarin anticoagulants, systemic cyclosporine, or certain other medications. * Pregnant or lactating women, or women intending to become pregnant. * Participants with diabetes mellitus that is poorly controlled. * Participants of Asian ancestry (having Filipino, Chinese, Japanese, Korean, Vietnamese, or Asian-Indian origin).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Percent Change in Triglycerides From Baseline to Week 8. | Baseline to 8 weeks | Triglycerides were measured in milligrams/deciliter. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change in High-Density Lipoprotein Cholesterol From Baseline to Week 8. | Baseline to 8 weeks | High-density lipoprotein cholesterol (HDL-C) was measured in milligrams/deciliter (mg/dL). |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
280 participants were randomized and treated at 84 sites in the United States and Puerto Rico between 23 July 2008 and 02 March 2011.
Participants by arm
| Arm | Count |
|---|---|
| ABT-335 Plus Rosuvastatin ABT-335 45 mg plus rosuvastatin 5 mg for 8 weeks, then ABT-335 45 mg plus rosuvastatin 10 mg for 8 weeks | 140 |
| Rosuvastatin Rosuvastatin 5 mg for 8 weeks then rosuvastatin 10 mg for 8 weeks | 140 |
| Total | 280 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 13 | 7 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 5 |
Baseline characteristics
| Characteristic | ABT-335 Plus Rosuvastatin | Rosuvastatin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 73 Participants | 92 Participants | 165 Participants |
| Age, Categorical Between 18 and 65 years | 67 Participants | 48 Participants | 115 Participants |
| Age Continuous | 65.1 years STANDARD_DEVIATION 10.35 | 67.4 years STANDARD_DEVIATION 11.15 | 66.2 years STANDARD_DEVIATION 10.8 |
| Region of Enrollment Puerto Rico | 11 participants | 8 participants | 19 participants |
| Region of Enrollment United States | 129 participants | 132 participants | 261 participants |
| Sex: Female, Male Female | 78 Participants | 71 Participants | 149 Participants |
| Sex: Female, Male Male | 62 Participants | 69 Participants | 131 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 54 / 140 | 60 / 140 |
| serious Total, serious adverse events | 9 / 140 | 11 / 140 |
Outcome results
Primary
Median Percent Change in Triglycerides From Baseline to Week 8.
Triglycerides were measured in milligrams/deciliter.
Time frame: Baseline to 8 weeks
Population: Full Analysis Set was used and was defined as all randomized participants who had both a baseline value and at least 1 postbaseline 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) |
|---|---|---|
| ABT-335 Plus Rosuvastatin | Median Percent Change in Triglycerides From Baseline to Week 8. | -38.0 percent change |
| Rosuvastatin | Median Percent Change in Triglycerides From Baseline to Week 8. | -22.4 percent change |
Comparison: The null hypothesis was that percent change in triglycerides (TG) from baseline to Week 8 in the ABT-335 45 mg plus rosuvastatin 5 mg treatment group is equal to percent change in TG from baseline to Week 8 in the rosuvastatin 5 mg plus placebo treatment group. A sample size of 140 participants per treatment group was used to provide 98% power to detect a difference between the combination therapy arm and the rosuvastatin monotherapy arm in the percent change from Baseline to Week 8 in TG.p-value: <0.001Wilcoxon rank-sum test
Secondary
Mean Percent Change in High-Density Lipoprotein Cholesterol From Baseline to Week 8.
High-density lipoprotein cholesterol (HDL-C) was measured in milligrams/deciliter (mg/dL).
Time frame: Baseline to 8 weeks
Population: Full Analysis Set was used and was defined as all randomized participants who had both a baseline value and at least 1 postbaseline 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 (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ABT-335 Plus Rosuvastatin | Mean Percent Change in High-Density Lipoprotein Cholesterol From Baseline to Week 8. | 16.9 percent change | Standard Error 1.44 |
| Rosuvastatin | Mean Percent Change in High-Density Lipoprotein Cholesterol From Baseline to Week 8. | 7.8 percent change | Standard Error 1.43 |
Comparison: The null hypothesis was that percent change in HDL-C from baseline to Week 8 in the ABT-335 45 mg plus rosuvastatin 5 mg treatment group is equal to percent change in HDL-C from baseline to Week 8 in the rosuvastatin 5 mg plus placebo treatment group. A sample size of 140 participants per treatment group was used to provide 82% power to detect a difference between the combination therapy arm and the rosuvastatin monotherapy arm in the percent change from Baseline to Week 8 in HDL-C.p-value: <0.001ANCOVA