Hypercholesterolemia
Conditions
Keywords
High Cholesterol
Brief summary
This is a multicenter study to evaluate the safety and efficacy of ezetimibe/simvastatin versus rosuvastatin in participants with high cholesterol.
Interventions
DRUGComparator: Placebo (unspecified)
rosuvastatin 10mg Placebo. The treatment duration will be 6 weeks.
ezetimibe/simvastatin 10/20mg. The treatment duration will be 6 weeks.
DRUGComparator : rosuvastatin calcium
rosuvastatin 10mg. The treatment duration will be 6 weeks.
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Participant is currently taking a statin medication for the treatment of high cholesterol * Participant has an LDL-C level that is greater than or equal to 100 mg/dl and less than or equal to 190 mg/dl
Exclusion criteria
* Women who are pregnant or nursing, or women who intend to become pregnant * Participant has any condition, situation, or is currently taking any medication that might pose a risk to the participant or interfere with participation in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Low Density Lipoprotein-Cholesterol (LDL-C) at Study Endpoint After Six Weeks of Treatment | Baseline and 6 weeks | Percent Change in LDL-C at study endpoint after six weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure \*100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Participants Achieving Designated Low Density Lipoprotein-Cholesterol (LDL-C) Levels After 6 Weeks of Treatment | after 6 weeks of treatment | The percentage of participants who achieved a target LDL-C goal of \< 100 mg/dL, of \<70 mg/dL, and of \<77 mg/dL at study endpoint after six weeks of treatment. The numerator is the number of participants in a treatment group who achieved a target LDL-C goal and the denominator is the total number of participants within that treatment group. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) | Baseline and 6 weeks | Percent change from baseline in HDL-C at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure \*100. |
| Percent Change From Baseline in Non-High Density Lipoprotein-Cholesterol (Non-HDL-C) | Baseline and 6 weeks | Percent change from baseline in non HDL-C at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure \*100. |
| Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C)/High Density Lipoprotein-Cholesterol (HDL-C) Ratio | Baseline and 6 weeks | Percent change from baseline in LDL-C/HDL-C ratio at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure \*100. |
| Percent Change From Baseline in Total Cholesterol | Baseline and 6 weeks | Percent change from baseline in total cholesterol at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure \*100. |
| Percent Change From Baseline in Apolipoprotein B | Baseline and 6 weeks | Percent change from baseline in apolipoprotein (Apo) B at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure \*100. |
| Percent Change From Baseline in High-sensitivity C (Hs-C) Reactive Protein | Baseline and 6 weeks | Percent change from baseline in hs-C reactive protein at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure \*100. |
| Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-Cholesterol (HDL-C) Ratio | Baseline and 6 weeks | Percent change from baseline in total cholesterol/HDL-C ratio at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure \*100. |
| Percent Change From Baseline in Triglycerides. | Baseline and 6 weeks | Percent change from baseline in triglycerides at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure \*100. |
Participant flow
Recruitment details
Phase IV First Participant In: 31-Mar-2007; Last Participant Last Visit 11-Mar-2008 85 centers worldwide (EX US) Eligible participants include those on a stable dose of one of the following: rosuvastatin 5 mg; simvastatin 20 mg, 40 mg; atorvastatin 10, 20 mg; pravastatin 40 mg; fluvastatin 80 mg.
Pre-assignment details
Eligible participants were randomized at Visit 2 (Week 6) to either a combination tablet of ezetimibe/simvastatin (10 mg/20 mg) plus a matching placebo for rosuvastatin 10 mg (Group 1) or rosuvastatin 10 mg plus a matching placebo for the combination tablet (Group 2) for a 6-week treatment period.
Participants by arm
| Arm | Count |
|---|---|
| Ezetemibe + Simvastatin Ezetemibe 10 mg + Simvastatin 20 mg plus a matching placebo for rosuvastatin 10 mg QD (once a day) for 6 weeks | 314 |
| Rosuvastatin Rosuvastatin 10 mg plus a matching placebo for the combination tablet QD (once a day) for 6 weeks | 304 |
| Total | 618 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 6 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 1 |
Baseline characteristics
| Characteristic | Ezetemibe + Simvastatin | Total | Rosuvastatin |
|---|---|---|---|
| Age, Continuous | 63.2 years | 63.15 years | 63.1 years |
| Apolipoprotein B | 1.20 mg/dL STANDARD_DEVIATION 0.2 | 1.19 mg/dL STANDARD_DEVIATION 0.21 | 1.18 mg/dL STANDARD_DEVIATION 0.21 |
| C Reactive Protein | 0.16 mg/dL STANDARD_DEVIATION 0.26 | 0.16 mg/dL STANDARD_DEVIATION 0.26 | 0.15 mg/dL STANDARD_DEVIATION 0.26 |
| High Density Lipoprotein-Cholesterol | 1.43 mg/dL STANDARD_DEVIATION 0.37 | 1.43 mg/dL STANDARD_DEVIATION 0.36 | 1.43 mg/dL STANDARD_DEVIATION 0.36 |
| Low Density Lipoprotein-Cholesterol (LDL-C) | 3.21 mg/dL STANDARD_DEVIATION 0.42 | 3.23 mg/dL STANDARD_DEVIATION 0.43 | 3.24 mg/dL STANDARD_DEVIATION 0.44 |
| Low Density Lipoprotein-Cholesterol (LDL-C):High Density Lipoprotein-Cholesterol (HDL-C) ratio | 2.38 LDL-C:HDL-C ratio STANDARD_DEVIATION 0.65 | 2.39 LDL-C:HDL-C ratio STANDARD_DEVIATION 0.65 | 2.40 LDL-C:HDL-C ratio STANDARD_DEVIATION 0.65 |
| Non-High Density Lipoprotein-Cholesterol (Non-HDL-C) | 3.95 mg/dL STANDARD_DEVIATION 0.55 | 3.95 mg/dL STANDARD_DEVIATION 0.55 | 3.95 mg/dL STANDARD_DEVIATION 0.56 |
| Race/Ethnicity, Customized Black | 0 participants | 2 participants | 2 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 37 Participants | 80 Participants | 43 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 277 Participants | 538 Participants | 261 Participants |
| Race/Ethnicity, Customized White | 314 participants | 616 participants | 302 participants |
| Sex: Female, Male Female | 129 Participants | 248 Participants | 119 Participants |
| Sex: Female, Male Male | 185 Participants | 370 Participants | 185 Participants |
| Total Cholesterol | 5.38 mg/dL STANDARD_DEVIATION 0.57 | 5.38 mg/dL STANDARD_DEVIATION 0.59 | 5.38 mg/dL STANDARD_DEVIATION 0.61 |
| Total cholesterol:High Density Lipoprotein-Cholesterol (HDL-C) ratio | 3.94 Total cholesterol:HDL-C ratio STANDARD_DEVIATION 0.89 | 3.95 Total cholesterol:HDL-C ratio STANDARD_DEVIATION 0.9 | 3.96 Total cholesterol:HDL-C ratio STANDARD_DEVIATION 0.9 |
| Triglycerides | 1.46 mg/dL STANDARD_DEVIATION 0.86 | 1.42 mg/dL STANDARD_DEVIATION 0.88 | 1.41 mg/dL STANDARD_DEVIATION 0.87 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / — | 30 / — |
| serious Total, serious adverse events | 3 / — | 5 / — |
Outcome results
Primary
Percent Change in Low Density Lipoprotein-Cholesterol (LDL-C) at Study Endpoint After Six Weeks of Treatment
Percent Change in LDL-C at study endpoint after six weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure \*100.
Time frame: Baseline and 6 weeks
Population: Full Analysis Set (FAS): The FAS population includes all randomized participants who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetemibe + Simvastatin | Percent Change in Low Density Lipoprotein-Cholesterol (LDL-C) at Study Endpoint After Six Weeks of Treatment | -27.66 percent change from baseline |
| Rosuvastatin | Percent Change in Low Density Lipoprotein-Cholesterol (LDL-C) at Study Endpoint After Six Weeks of Treatment | -16.94 percent change from baseline |
p-value: <=0.00195% CI: [-14.1, -7.33]ANOVA
Secondary
The Percentage of Participants Achieving Designated Low Density Lipoprotein-Cholesterol (LDL-C) Levels After 6 Weeks of Treatment
The percentage of participants who achieved a target LDL-C goal of \< 100 mg/dL, of \<70 mg/dL, and of \<77 mg/dL at study endpoint after six weeks of treatment. The numerator is the number of participants in a treatment group who achieved a target LDL-C goal and the denominator is the total number of participants within that treatment group.
Time frame: after 6 weeks of treatment
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ezetemibe + Simvastatin | The Percentage of Participants Achieving Designated Low Density Lipoprotein-Cholesterol (LDL-C) Levels After 6 Weeks of Treatment | LDL-C <70 | 25.25 Percent of participant population |
| Ezetemibe + Simvastatin | The Percentage of Participants Achieving Designated Low Density Lipoprotein-Cholesterol (LDL-C) Levels After 6 Weeks of Treatment | LDL-C <100 | 72.46 Percent of participant population |
| Rosuvastatin | The Percentage of Participants Achieving Designated Low Density Lipoprotein-Cholesterol (LDL-C) Levels After 6 Weeks of Treatment | LDL-C <100 | 56.23 Percent of participant population |
| Rosuvastatin | The Percentage of Participants Achieving Designated Low Density Lipoprotein-Cholesterol (LDL-C) Levels After 6 Weeks of Treatment | LDL-C <70 | 11.11 Percent of participant population |
Comparison: Percentage of Participants who Attained Target LDL-C Goal of \< 100 mg/dL (2.59 mmol/L)p-value: <=0.00195% CI: [1.5, 3]Regression, Logistic
Comparison: Percentage of Participants who Attained Target LDL-C Goal of \< 70 mg/dL (1.81 mmol/L)p-value: <=0.00195% CI: [1.8, 4.4]Regression, Logistic
Other Pre-specified
Percent Change From Baseline in Apolipoprotein B
Percent change from baseline in apolipoprotein (Apo) B at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure \*100.
Time frame: Baseline and 6 weeks
Population: Full Analysis Set (FAS): The FAS population includes all randomized participants who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetemibe + Simvastatin | Percent Change From Baseline in Apolipoprotein B | -17.87 percent change from baseline |
| Rosuvastatin | Percent Change From Baseline in Apolipoprotein B | -9.77 percent change from baseline |
p-value: <=0.00195% CI: [-10.91, -5.3]ANOVA
Other Pre-specified
Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C)
Percent change from baseline in HDL-C at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure \*100.
Time frame: Baseline and 6 weeks
Population: Full Analysis Set (FAS): The FAS population includes all randomized participants who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetemibe + Simvastatin | Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) | 2.12 percent change from baseline |
| Rosuvastatin | Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) | 3.03 percent change from baseline |
p-value: 0.43395% CI: [-3.21, 1.38]ANOVA
Other Pre-specified
Percent Change From Baseline in High-sensitivity C (Hs-C) Reactive Protein
Percent change from baseline in hs-C reactive protein at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure \*100.
Time frame: Baseline and 6 weeks
Population: Full Analysis Set (FAS): The FAS population includes all randomized participants who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ezetemibe + Simvastatin | Percent Change From Baseline in High-sensitivity C (Hs-C) Reactive Protein | -8.33 percent change from baseline |
| Rosuvastatin | Percent Change From Baseline in High-sensitivity C (Hs-C) Reactive Protein | 0.00 percent change from baseline |
p-value: 0.17295% CI: [-16.67, 2.87]Nonparametric ANOVA
Other Pre-specified
Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C)/High Density Lipoprotein-Cholesterol (HDL-C) Ratio
Percent change from baseline in LDL-C/HDL-C ratio at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure \*100.
Time frame: Baseline and 6 weeks
Population: Full Analysis Set (FAS): The FAS population includes all randomized participants who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetemibe + Simvastatin | Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C)/High Density Lipoprotein-Cholesterol (HDL-C) Ratio | -27.41 percent change from baseline |
| Rosuvastatin | Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C)/High Density Lipoprotein-Cholesterol (HDL-C) Ratio | -17.82 percent change from baseline |
p-value: <=0.00195% CI: [-13.49, -5.69]ANOVA
Other Pre-specified
Percent Change From Baseline in Non-High Density Lipoprotein-Cholesterol (Non-HDL-C)
Percent change from baseline in non HDL-C at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure \*100.
Time frame: Baseline and 6 weeks
Population: Full Analysis Set (FAS): The FAS population includes all randomized participants who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetemibe + Simvastatin | Percent Change From Baseline in Non-High Density Lipoprotein-Cholesterol (Non-HDL-C) | -23.42 percent change from baseline |
| Rosuvastatin | Percent Change From Baseline in Non-High Density Lipoprotein-Cholesterol (Non-HDL-C) | -14.01 percent change from baseline |
p-value: <=0.00195% CI: [-12.5, -6.31]ANOVA
Other Pre-specified
Percent Change From Baseline in Total Cholesterol
Percent change from baseline in total cholesterol at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure \*100.
Time frame: Baseline and 6 weeks
Population: Full Analysis Set (FAS): The FAS population includes all randomized participants who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetemibe + Simvastatin | Percent Change From Baseline in Total Cholesterol | -17.53 percent change from baseline |
| Rosuvastatin | Percent Change From Baseline in Total Cholesterol | -10.33 percent change from baseline |
p-value: <=0.00195% CI: [-9.56, -4.84]ANOVA
Other Pre-specified
Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-Cholesterol (HDL-C) Ratio
Percent change from baseline in total cholesterol/HDL-C ratio at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure \*100.
Time frame: Baseline and 6 weeks
Population: Full Analysis Set (FAS): The FAS population includes all randomized participants who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetemibe + Simvastatin | Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-Cholesterol (HDL-C) Ratio | -17.76 percent change from baseline |
| Rosuvastatin | Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-Cholesterol (HDL-C) Ratio | -11.51 percent change from baseline |
p-value: <=0.00195% CI: [-9.07, -3.43]ANOVA
Other Pre-specified
Percent Change From Baseline in Triglycerides.
Percent change from baseline in triglycerides at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure \*100.
Time frame: Baseline and 6 weeks
Population: Full Analysis Set (FAS): The FAS population includes all randomized participants who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ezetemibe + Simvastatin | Percent Change From Baseline in Triglycerides. | -11.00 percent change from baseline |
| Rosuvastatin | Percent Change From Baseline in Triglycerides. | -5.26 percent change from baseline |
p-value: 0.05695% CI: [-9.56, -0.3]Nonparametric ANOVA