Hypercholesterolemia, Dyslipidemia
Conditions
Brief summary
The purpose of this study is to evaluate the safety and efficacy of ABT-335 and rosuvastatin calcium combination therapy to monotherapy in subjects with dyslipidemia.
Detailed description
There are 3 treatment groups in the study: ABT-335 135 mg in combination with rosuvastatin 5 mg, ABT-335 135 mg monotherapy, and rosuvastatin 5 mg monotherapy. The 3 primary outcome measures only compare 2 of the treatment groups for each variable (mean percent change in HDL-C and TG comparing ABT-335 135 mg in combination with rosuvastatin 5 mg to rosuvastatin 5 mg monotherapy, and mean percent change in LDL-C comparing ABT-335 135 mg in combination with rosuvastatin 5 mg to ABT-335 135 mg monotherapy. The 6 secondary outcome measures only compare 2 of the treatment groups for each variable (mean percent change in Non-HDL-C comparing ABT-335 135 mg in combination with rosuvastatin 5 mg to ABT-335 135 mg monotherapy, mean percent change in Non-HDL-C, VLDL-C, ApoB, and Total Cholesterol comparing ABT-335 135 mg in combination with rosuvastatin 5 mg to rosuvastatin 5 mg monotherapy, and median percent change in hsCRP comparing ABT-335 135 mg in combination with rosuvastatin 5 mg to rosuvastatin 5 mg monotherapy).
Interventions
ABT-335 135 mg in combination with rosuvastatin calcium 5 mg administered orally, once daily for 12 weeks
DRUGABT-335
ABT-335 135 mg monotherapy administered orally, once daily for 12 weeks
Rosuvastatin calcium 5 mg monotherapy administered orally, once daily for 12 weeks
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult male and female participants who voluntarily sign the informed consent. * Fasting lipid results following greater than 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. * Participant must agree to utilize adequate birth control methods and adhere to the American Heart Association (AHA) diet.
Exclusion criteria
* Participants with unstable medical conditions, medical conditions considered inappropriate in a clinical trial, or participants who are taking excluded concomitant medications are not allowed in the study. * Participants receiving coumarin anticoagulants or systemic cyclosporine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change From Baseline to the Final Visit in High-density Lipoprotein Cholesterol (HDL-C) (Full Analysis Set) | Baseline to 12 Weeks | The mean percent change from baseline to the final visit in High-density lipoprotein cholesterol (HDL-C), with ABT-335 135 mg in combination with rosuvastatin 5 mg versus rosuvastatin 5 mg monotherapy. |
| Mean Percent Change From Baseline to the Final Visit in Triglycerides (Full Analysis Set) | Baseline to 12 Weeks | The mean percent change from baseline to the final visit in triglycerides, with ABT-335 135 mg in combination with rosuvastatin 5 mg versus rosuvastatin 5 mg monotherapy. |
| Mean Percent Change From Baseline to the Final Visit in Low-density Lipoprotein Cholesterol (LDL-C) (Full Analysis Set) | Baseline to 12 Weeks | The mean percent change from baseline to the final visit in low-density lipoprotein cholesterol (LDL-C), with ABT-335 135 mg in combination with rosuvastatin 5 mg versus ABT-335 135 mg monotherapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change From Baseline to the Final Visit in Apolipoprotein B (ApoB) (Full Analysis Set) | Baseline to 12 Weeks | The mean percent change from baseline to the final visit in apolipoprotein B (ApoB), with ABT-335 135 mg in combination with rosuvastatin 5 mg versus rosuvastatin 5 mg monotherapy. |
| Mean Percent Change From Baseline to the Final Visit in Non-high-density Lipoprotein Cholesterol (Non-HDL-C), With ABT-335 135 mg in Combination With Rosuvastatin 5 mg Versus ABT-335 135 mg Monotherapy (Full Analysis Set) | Baseline to 12 Weeks | The mean percent change from baseline to the final visit in non-high-density lipoprotein cholesterol (non-HDL-C), with ABT-335 135 mg in combination with rosuvastatin 5 mg versus ABT-335 135 mg monotherapy. |
| Mean Percent Change From Baseline to the Final Visit in Total Cholesterol (Full Analysis Set) | Baseline to 12 Weeks | The mean percent change from baseline to the final visit in total cholesterol, with ABT-335 135 mg in combination with rosuvastatin 5 mg versus rosuvastatin 5 mg monotherapy. |
| Median Percent Change From Baseline to the Final Visit in High Sensitivity C-reactive Protein (hsCRP) (Full Analysis Set) | Baseline to 12 Weeks | The median percent change from baseline to the final visit in high sensitivity C-reactive protein (hsCRP), with ABT-335 135 mg in combination with rosuvastatin 5 mg versus rosuvastatin 5 mg monotherapy. |
| Mean Percent Change From Baseline to the Final Visit in Non-high-density Lipoprotein Cholesterol (Non-HDL-C), With ABT-335 135 mg in Combination With Rosuvastatin 5 mg Versus Rosuvastatin 5 mg Monotherapy (Full Analysis Set) | Baseline to 12 Weeks | The mean percent change from baseline to the final visit in non-high-density lipoprotein cholesterol (non-HDL-C), with ABT-335 135 mg in combination with rosuvastatin 5 mg versus rosuvastatin 5 mg monotherapy. |
| Mean Percent Change From Baseline to the Final Visit in Very-low-density Lipoprotein Cholesterol (VLDL-C) (Full Analysis Set) | Baseline to 12 Weeks | The mean percent change from baseline to the final visit in very-low-density lipoprotein cholesterol (VLDL-C), with ABT-335 135 mg in combination with rosuvastatin 5 mg versus rosuvastatin 5 mg monotherapy. |
Countries
United States
Participant flow
Recruitment details
760 participants were randomized at 144 sites in the United States, and 758 participants were treated between 07 June 2007 and 10 February 2008. Two participants were randomized but not treated: 1 was lost to follow-up and 1 was withdrawn at the investigator's discretion.
Pre-assignment details
A total of 168 study sites screened participants, wtih 144 of these sites randomizing participants.
Participants by arm
| Arm | Count |
|---|---|
| ABT-335 and Rosuvastatin Calcium ABT-335 135 mg in combination with rosuvastatin calcium 5 mg administered orally, once daily for 12 weeks | 253 |
| ABT-335 ABT-335 135 mg monotherapy administered orally, once daily for 12 weeks | 254 |
| Rosuvastatin Calcium Rosuvastatin calcium 5 mg monotherapy administered orally, once daily for 12 weeks | 251 |
| Total | 758 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 21 | 18 | 11 |
| Overall Study | Coordinator error | 1 | 0 | 0 |
| Overall Study | Exclusion criteria violation | 2 | 0 | 0 |
| Overall Study | Lost to Follow-up | 2 | 2 | 3 |
| Overall Study | Participation in another ABT-335 trial | 1 | 0 | 0 |
| Overall Study | Patient randomized in error | 1 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | Sponsor request | 0 | 1 | 0 |
| Overall Study | Subject moved out of town | 1 | 0 | 0 |
| Overall Study | Subject noncompliance | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 11 | 11 | 5 |
Baseline characteristics
| Characteristic | ABT-335 | Rosuvastatin Calcium | ABT-335 and Rosuvastatin Calcium | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 51 Participants | 46 Participants | 59 Participants | 156 Participants |
| Age, Categorical Between 18 and 65 years | 203 Participants | 205 Participants | 194 Participants | 602 Participants |
| Age Continuous | 54.4 years STANDARD_DEVIATION 11.24 | 55.3 years STANDARD_DEVIATION 10.71 | 56.2 years STANDARD_DEVIATION 11.3 | 55.3 years STANDARD_DEVIATION 11.1 |
| Region of Enrollment United States | 254 participants | 251 participants | 253 participants | 758 participants |
| Sex: Female, Male Female | 144 Participants | 150 Participants | 161 Participants | 455 Participants |
| Sex: Female, Male Male | 110 Participants | 101 Participants | 92 Participants | 303 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 | 52 / 253 | 41 / 254 | 45 / 251 |
| serious Total, serious adverse events | 7 / 253 | 6 / 254 | 4 / 251 |
Outcome results
Primary
Mean Percent Change From Baseline to the Final Visit in High-density Lipoprotein Cholesterol (HDL-C) (Full Analysis Set)
The mean percent change from baseline to the final visit in High-density lipoprotein cholesterol (HDL-C), with ABT-335 135 mg in combination with rosuvastatin 5 mg versus rosuvastatin 5 mg monotherapy.
Time frame: Baseline to 12 Weeks
Population: Full Analysis Set was used and was defined as all randomized participants who had both a baseline and at least 1 post-baseline value for high-density lipoprotein cholesterol. 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 |
|---|---|---|---|
| ABT-335 and Rosuvastatin Calcium | Mean Percent Change From Baseline to the Final Visit in High-density Lipoprotein Cholesterol (HDL-C) (Full Analysis Set) | 23.0 percent change | Standard Error 1.33 |
| Rosuvastatin Calcium | Mean Percent Change From Baseline to the Final Visit in High-density Lipoprotein Cholesterol (HDL-C) (Full Analysis Set) | 12.4 percent change | Standard Error 1.32 |
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 (LDL-C), with ABT-335 135 mg in combination with rosuvastatin 5 mg versus ABT-335 135 mg monotherapy.
Time frame: Baseline to 12 Weeks
Population: Full Analysis Set was used and was defined as all randomized participants who had both a baseline value and at least 1 post-baseline value for low-density lipoprotein cholesterol. 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 |
|---|---|---|---|
| ABT-335 and Rosuvastatin Calcium | Mean Percent Change From Baseline to the Final Visit in Low-density Lipoprotein Cholesterol (LDL-C) (Full Analysis Set) | -28.7 percent change | Standard Error 1.33 |
| Rosuvastatin Calcium | Mean Percent Change From Baseline to the Final Visit in Low-density Lipoprotein Cholesterol (LDL-C) (Full Analysis Set) | -4.1 percent change | Standard Error 1.31 |
Primary
Mean Percent Change From Baseline to the Final Visit in Triglycerides (Full Analysis Set)
The mean percent change from baseline to the final visit in triglycerides, with ABT-335 135 mg in combination with rosuvastatin 5 mg versus rosuvastatin 5 mg monotherapy.
Time frame: Baseline to 12 Weeks
Population: Full Analysis Set was used and was 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 (MEAN) | Dispersion |
|---|---|---|---|
| ABT-335 and Rosuvastatin Calcium | Mean Percent Change From Baseline to the Final Visit in Triglycerides (Full Analysis Set) | -40.3 percent change | Standard Error 1.89 |
| Rosuvastatin Calcium | Mean Percent Change From Baseline to the Final Visit in Triglycerides (Full Analysis Set) | -17.5 percent change | Standard Error 1.88 |
Secondary
Mean Percent Change From Baseline to the Final Visit in Apolipoprotein B (ApoB) (Full Analysis Set)
The mean percent change from baseline to the final visit in apolipoprotein B (ApoB), with ABT-335 135 mg in combination with rosuvastatin 5 mg versus rosuvastatin 5 mg monotherapy.
Time frame: Baseline to 12 Weeks
Population: Full Analysis Set was used and was defined as all randomized participants who had both a baseline value and at least 1 post-baseline value for ApoB. 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 |
|---|---|---|---|
| ABT-335 and Rosuvastatin Calcium | Mean Percent Change From Baseline to the Final Visit in Apolipoprotein B (ApoB) (Full Analysis Set) | -30.9 percent change | Standard Error 1 |
| Rosuvastatin Calcium | Mean Percent Change From Baseline to the Final Visit in Apolipoprotein B (ApoB) (Full Analysis Set) | -26.4 percent change | Standard Error 0.99 |
Secondary
Mean Percent Change From Baseline to the Final Visit in Non-high-density Lipoprotein Cholesterol (Non-HDL-C), With ABT-335 135 mg in Combination With Rosuvastatin 5 mg Versus ABT-335 135 mg Monotherapy (Full Analysis Set)
The mean percent change from baseline to the final visit in non-high-density lipoprotein cholesterol (non-HDL-C), with ABT-335 135 mg in combination with rosuvastatin 5 mg versus ABT-335 135 mg monotherapy.
Time frame: Baseline to 12 Weeks
Population: Full Analysis Set was used and was defined as all randomized participants who had both a baseline value and at least 1 post-baseline value for non-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 |
|---|---|---|---|
| ABT-335 and Rosuvastatin Calcium | Mean Percent Change From Baseline to the Final Visit in Non-high-density Lipoprotein Cholesterol (Non-HDL-C), With ABT-335 135 mg in Combination With Rosuvastatin 5 mg Versus ABT-335 135 mg Monotherapy (Full Analysis Set) | -37.4 percent change | Standard Error 1.06 |
| Rosuvastatin Calcium | Mean Percent Change From Baseline to the Final Visit in Non-high-density Lipoprotein Cholesterol (Non-HDL-C), With ABT-335 135 mg in Combination With Rosuvastatin 5 mg Versus ABT-335 135 mg Monotherapy (Full Analysis Set) | -16.0 percent change | Standard Error 1.05 |
Secondary
Mean Percent Change From Baseline to the Final Visit in Non-high-density Lipoprotein Cholesterol (Non-HDL-C), With ABT-335 135 mg in Combination With Rosuvastatin 5 mg Versus Rosuvastatin 5 mg Monotherapy (Full Analysis Set)
The mean percent change from baseline to the final visit in non-high-density lipoprotein cholesterol (non-HDL-C), with ABT-335 135 mg in combination with rosuvastatin 5 mg versus rosuvastatin 5 mg monotherapy.
Time frame: Baseline to 12 Weeks
Population: Full Analysis Set was used and was defined as all randomized participants who had both a baseline value and at least 1 post-baseline value for non-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 |
|---|---|---|---|
| ABT-335 and Rosuvastatin Calcium | Mean Percent Change From Baseline to the Final Visit in Non-high-density Lipoprotein Cholesterol (Non-HDL-C), With ABT-335 135 mg in Combination With Rosuvastatin 5 mg Versus Rosuvastatin 5 mg Monotherapy (Full Analysis Set) | -37.4 percent change | Standard Error 1.06 |
| Rosuvastatin Calcium | Mean Percent Change From Baseline to the Final Visit in Non-high-density Lipoprotein Cholesterol (Non-HDL-C), With ABT-335 135 mg in Combination With Rosuvastatin 5 mg Versus Rosuvastatin 5 mg Monotherapy (Full Analysis Set) | -31.8 percent change | Standard Error 1.05 |
Secondary
Mean Percent Change From Baseline to the Final Visit in Total Cholesterol (Full Analysis Set)
The mean percent change from baseline to the final visit in total cholesterol, with ABT-335 135 mg in combination with rosuvastatin 5 mg versus rosuvastatin 5 mg monotherapy.
Time frame: Baseline to 12 Weeks
Population: Full Analysis Set was used and was defined as all randomized participants who had both a baseline value and at least 1 post-baseline value for total cholesterol. 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 |
|---|---|---|---|
| ABT-335 and Rosuvastatin Calcium | Mean Percent Change From Baseline to the Final Visit in Total Cholesterol (Full Analysis Set) | -28.1 percent change | Standard Error 0.85 |
| Rosuvastatin Calcium | Mean Percent Change From Baseline to the Final Visit in Total Cholesterol (Full Analysis Set) | -25.0 percent change | Standard Error 0.84 |
Secondary
Mean Percent Change From Baseline to the Final Visit in Very-low-density Lipoprotein Cholesterol (VLDL-C) (Full Analysis Set)
The mean percent change from baseline to the final visit in very-low-density lipoprotein cholesterol (VLDL-C), with ABT-335 135 mg in combination with rosuvastatin 5 mg versus rosuvastatin 5 mg monotherapy.
Time frame: Baseline to 12 Weeks
Population: Full Analysis Set was used and was defined as all randomized participants who had both a baseline value and at least 1 post-baseline value for VLDL-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 |
|---|---|---|---|
| ABT-335 and Rosuvastatin Calcium | Mean Percent Change From Baseline to the Final Visit in Very-low-density Lipoprotein Cholesterol (VLDL-C) (Full Analysis Set) | -41.3 percent change | Standard Error 3.56 |
| Rosuvastatin Calcium | Mean Percent Change From Baseline to the Final Visit in Very-low-density Lipoprotein Cholesterol (VLDL-C) (Full Analysis Set) | -22.2 percent change | Standard Error 3.53 |
Secondary
Median Percent Change From Baseline to the Final Visit in High Sensitivity C-reactive Protein (hsCRP) (Full Analysis Set)
The median percent change from baseline to the final visit in high sensitivity C-reactive protein (hsCRP), with ABT-335 135 mg in combination with rosuvastatin 5 mg versus rosuvastatin 5 mg monotherapy.
Time frame: Baseline to 12 Weeks
Population: Full Analysis Set was used and was defined as all randomized participants who had both a baseline value and at least 1 post-baseline value for hsCRP. 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 and Rosuvastatin Calcium | Median Percent Change From Baseline to the Final Visit in High Sensitivity C-reactive Protein (hsCRP) (Full Analysis Set) | -28.0 percent change |
| Rosuvastatin Calcium | Median Percent Change From Baseline to the Final Visit in High Sensitivity C-reactive Protein (hsCRP) (Full Analysis Set) | -11.4 percent change |