Hyperlipidemia
Conditions
Keywords
Proprotein convertase subtilisin/kexin type 9 (PCSK9), Cholesterol, High Cholesterol, Raised Cholesterol, Elevated Cholesterol, Statin intolerant, Hypercholesterolemia
Brief summary
The primary objective was to evaluate the effect of 12 weeks of subcutaneous evolocumab (AMG 145), compared with ezetimibe, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in patients with hypercholesterolemia unable to tolerate an effective dose of a statin.
Interventions
BIOLOGICALEvolocumab
Administered by subcutaneous injection
DRUGEzetimibe
Administered orally once a day
Administered by subcutaneous injection
Sponsors
Amgen
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 75 Years
Healthy volunteers
No
Inclusion criteria
* Male or female ≥ 18 to ≤ 75 years of age * On a statin or a low dose statin with stable dose for at least 4 weeks * Lipid lowering therapy has been stable prior to enrollment * Fasting triglycerides must be \< 400 mg/dL. * Subject not at LDL-C goal
Exclusion criteria
* New York Heart Association (NYHA) III or IV heart failure or known left ventricular ejection fraction \< 30% * Uncontrolled cardiac arrhythmia * Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months prior to randomization * Type 1 diabetes or newly diagnosed type 2 diabetes (HbA1c \> 8.5%) * Uncontrolled hypertension
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | Baseline and Week 12 | LDL-C was measured using ultracentrifugation. Least squares (LS) means are based off an analysis of covariance (ANCOVA) model which includes treatment group (3 evolocumab alone dose groups and the ezetimibe group) and stratification factors as covariates. |
| Percent Change From Baseline in LDL-C at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe | Baseline and Week 12 | LDL-C was measured using ultracentrifugation. LS means are based off an ANCOVA model which includes treatment group (evolocumab + ezetimibe and ezetimibe alone) and stratification factors as covariates. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Non-HDL-C at Week 12 | Baseline and Week 12 | LS means are based off an ANCOVA model which includes treatment group (3 evolocumab alone dose groups and the ezetimibe group) and stratification factors as covariates. |
| Percent Change From Baseline in Non-HDL-C at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe | Baseline and Week 12 | LS means are based off an ANCOVA model which includes treatment group (evolocumab + ezetimibe and ezetimibe alone) and stratification factors as covariates. |
| Percent Change From Baseline in Apolipoprotein B at Week 12 | Baseline and Week 12 | LS means are based off an ANCOVA model which includes treatment group (3 evolocumab alone dose groups and the ezetimibe group) and stratification factors as covariates. |
| Percent Change From Baseline in Apolipoprotein B at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe | Baseline and Week 12 | LS means are based off an ANCOVA model which includes treatment group (evoloumab + ezetimibe and ezetimibe) and stratification factors as covariates. |
| Change From Baseline in LDL-C at Week 12 | Baseline and Week 12 | LDL-C was measured using ultracentrifugation. LS means are based off an ANCOVA model which includes treatment group (3 evolocumab alone dose groups and the ezetimibe group) and stratification factors as covariates. |
| Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe | Baseline and Week 12 | LS means are based off an ANCOVA model which includes treatment group (evoloumab + ezetimibe and ezetimibe alone) and stratification factors as covariates. |
| Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12 | Baseline and Week 12 | LS means are based off an ANCOVA model which includes treatment group (3 evolocumab alone dose groups and the ezetimibe group) and stratification factors as covariates. |
| Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe | Baseline and Week 12 | LS means are based off an ANCOVA model which includes treatment group (evoloumab + ezetimibe and ezetimibe alone) and stratification factors as covariates. |
| Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12 | Baseline and Week 12 | LS means are based off an ANCOVA model which includes treatment group (3 evolocumab alone dose groups and the ezetimibe group) and stratification factors as covariates. |
| Change From Baseline in LDL-C at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe | Baseline and Week 12 | LDL-C was measured using ultracentrifugation. LS means are based off an ANCOVA model which includes treatment group (evoloumab + ezetimibe and ezetimibe alone) and stratification factors as covariates. |
Countries
Australia, Belgium, Canada, Denmark, Finland, Spain, Sweden, United States
Participant flow
Recruitment details
The study enrolled adults aged 18 to 75 years with hypercholesterolemia who were statin intolerant and with low-density lipoprotein cholesterol (LDL-C) levels above risk-based goals recommended by the National Cholesterol Education Program. The first patient enrolled on 28 July 2011; last patient enrolled 14 February 2012.
Pre-assignment details
Randomization was stratified by screening LDL-C level (\< 130 mg/dL \[3.4 mmol/L\] or ≥ 130 mg/dL) and statin use at baseline (yes or no).
Participants by arm
| Arm | Count |
|---|---|
| Ezetimibe Participants received placebo subcutaneous injection once every 4 weeks and 10 mg ezetimibe orally once a day for 12 weeks. | 32 |
| Evolocumab + Ezetimibe Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks and 10 mg ezetimibe orally once a day for 12 weeks. | 30 |
| Evolocumab 280 mg Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. | 32 |
| Evolocumab 350 mg Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. | 31 |
| Evolocumab 420 mg Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. | 32 |
| Total | 157 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Ezetimibe | Evolocumab 280 mg | Evolocumab 350 mg | Evolocumab 420 mg | Total | Evolocumab + Ezetimibe |
|---|---|---|---|---|---|---|
| Age, Continuous | 62.4 years STANDARD_DEVIATION 6.6 | 62.2 years STANDARD_DEVIATION 10.1 | 62.3 years STANDARD_DEVIATION 9.1 | 60.0 years STANDARD_DEVIATION 8.6 | 61.8 years STANDARD_DEVIATION 8.4 | 62.0 years STANDARD_DEVIATION 7.2 |
| Apolipoprotein B/Apolipoprotein A-1 Ratio | 0.841 ratio STANDARD_DEVIATION 0.23 | 0.906 ratio STANDARD_DEVIATION 0.265 | 0.916 ratio STANDARD_DEVIATION 0.332 | 1.055 ratio STANDARD_DEVIATION 0.388 | 0.921 ratio STANDARD_DEVIATION 0.319 | 0.882 ratio STANDARD_DEVIATION 0.332 |
| Apolipoprotein B Concentration | 138.0 mg/dL STANDARD_DEVIATION 21.7 | 143.0 mg/dL STANDARD_DEVIATION 30.6 | 144.9 mg/dL STANDARD_DEVIATION 33.9 | 150.8 mg/dL STANDARD_DEVIATION 34.1 | 143.2 mg/dL STANDARD_DEVIATION 30.9 | 138.8 mg/dL STANDARD_DEVIATION 33.1 |
| LDL-C Concentration | 182.9 mg/dL STANDARD_DEVIATION 36.4 | 194.8 mg/dL STANDARD_DEVIATION 48.1 | 190.3 mg/dL STANDARD_DEVIATION 47.8 | 203.5 mg/dL STANDARD_DEVIATION 60.3 | 193.2 mg/dL STANDARD_DEVIATION 51 | 194.4 mg/dL STANDARD_DEVIATION 60.1 |
| Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Concentration | 213.7 mg/dL STANDARD_DEVIATION 40.4 | 225.5 mg/dL STANDARD_DEVIATION 53.3 | 222.9 mg/dL STANDARD_DEVIATION 55.8 | 240.6 mg/dL STANDARD_DEVIATION 63.9 | 224.6 mg/dL STANDARD_DEVIATION 55.3 | 219.8 mg/dL STANDARD_DEVIATION 60.5 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 2 participants | 1 participants | 0 participants | 0 participants | 8 participants | 5 participants |
| Race/Ethnicity, Customized Black or African American | 2 participants | 2 participants | 2 participants | 1 participants | 8 participants | 1 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 participants | 0 participants | 0 participants | 0 participants | 2 participants | 0 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 30 participants | 32 participants | 31 participants | 32 participants | 155 participants | 30 participants |
| Race/Ethnicity, Customized Other | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized White | 28 participants | 28 participants | 29 participants | 30 participants | 139 participants | 24 participants |
| Sex: Female, Male Female | 18 Participants | 18 Participants | 21 Participants | 20 Participants | 100 Participants | 23 Participants |
| Sex: Female, Male Male | 14 Participants | 14 Participants | 10 Participants | 12 Participants | 57 Participants | 7 Participants |
| Stratification Factor: Baseline Use of Statin No | 26 participants | 27 participants | 27 participants | 27 participants | 133 participants | 26 participants |
| Stratification Factor: Baseline Use of Statin Yes | 6 participants | 5 participants | 4 participants | 5 participants | 24 participants | 4 participants |
| Stratification Factor: LDL-C Level < 130 mg/dL | 2 participants | 2 participants | 2 participants | 2 participants | 9 participants | 1 participants |
| Stratification Factor: LDL-C Level ≥ 130 mg/dL | 30 participants | 30 participants | 29 participants | 30 participants | 148 participants | 29 participants |
| Total Cholesterol/HDL-C Ratio | 4.907 ratio STANDARD_DEVIATION 1.553 | 5.287 ratio STANDARD_DEVIATION 1.816 | 5.444 ratio STANDARD_DEVIATION 2.308 | 6.438 ratio STANDARD_DEVIATION 2.834 | 5.438 ratio STANDARD_DEVIATION 2.265 | 5.093 ratio STANDARD_DEVIATION 2.416 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 16 / 32 | 19 / 32 | 10 / 31 | 12 / 32 | 18 / 30 |
| serious Total, serious adverse events | 0 / 32 | 2 / 32 | 1 / 31 | 1 / 32 | 0 / 30 |
Outcome results
Primary
Percent Change From Baseline in LDL-C at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe
LDL-C was measured using ultracentrifugation. LS means are based off an ANCOVA model which includes treatment group (evolocumab + ezetimibe and ezetimibe alone) and stratification factors as covariates.
Time frame: Baseline and Week 12
Population: Full analysis set; Missing UC LDL-C at Week 12 was imputed using LOCF and calculated LDL-C.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in LDL-C at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe | -15.70 percent change | Standard Error 3.98 |
| Evolocumab 280 mg | Percent Change From Baseline in LDL-C at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe | -62.98 percent change | Standard Error 4.22 |
Comparison: The null hypothesis was that there was no mean difference in the percent change from Baseline at Week 12 in LDL-C between evolocumab + ezetimibe and ezetimibe alone, and the alternative hypothesis was that a mean difference did exist.p-value: <0.00195% CI: [-53.73, -40.84]ANCOVA
Primary
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
LDL-C was measured using ultracentrifugation. Least squares (LS) means are based off an analysis of covariance (ANCOVA) model which includes treatment group (3 evolocumab alone dose groups and the ezetimibe group) and stratification factors as covariates.
Time frame: Baseline and Week 12
Population: Full analysis set; Missing ultracentrifugation (UC) LDL-C at Week 12 was imputed using last observation carried forward (LOCF) and calculated LDL-C.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | -14.76 percent change | Standard Error 3.94 |
| Evolocumab 280 mg | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | -40.77 percent change | Standard Error 3.96 |
| Evolocumab 350 mg | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | -42.58 percent change | Standard Error 4.01 |
| Evolocumab 420 mg | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | -50.70 percent change | Standard Error 3.98 |
Comparison: The null hypothesis was that there was no mean difference in the percent change from Baseline at Week 12 in LDL-C between evolocumab and ezetimibe, and the alternative hypothesis was that a mean difference did exist.p-value: <0.00195% CI: [-44.08, -27.8]ANCOVA
Comparison: The null hypothesis was that there was no mean difference in the percent change from Baseline at Week 12 in LDL-C between evolocumab and ezetimibe, and the alternative hypothesis was that a mean difference did exist.p-value: <0.00195% CI: [-35.97, -19.67]ANCOVA
Comparison: The null hypothesis was that there was no mean difference in the percent change from Baseline at Week 12 in LDL-C between evolocumab and ezetimibe, and the alternative hypothesis was that a mean difference did exist.p-value: <0.00195% CI: [-34.08, -17.93]ANCOVA
Secondary
Change From Baseline in LDL-C at Week 12
LDL-C was measured using ultracentrifugation. LS means are based off an ANCOVA model which includes treatment group (3 evolocumab alone dose groups and the ezetimibe group) and stratification factors as covariates.
Time frame: Baseline and Week 12
Population: Full analysis set; Missing UC LDL-C at Week 12 was imputed using LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Change From Baseline in LDL-C at Week 12 | -14.2 mg/dL | Standard Error 8.9 |
| Evolocumab 280 mg | Change From Baseline in LDL-C at Week 12 | -66.8 mg/dL | Standard Error 8.9 |
| Evolocumab 350 mg | Change From Baseline in LDL-C at Week 12 | -69.7 mg/dL | Standard Error 9.1 |
| Evolocumab 420 mg | Change From Baseline in LDL-C at Week 12 | -90.8 mg/dL | Standard Error 9 |
p-value: <0.00195% CI: [-94.9, -58.3]ANCOVA
p-value: <0.00195% CI: [-74, -37.1]ANCOVA
p-value: <0.00195% CI: [-70.8, -34.5]ANCOVA
Secondary
Change From Baseline in LDL-C at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe
LDL-C was measured using ultracentrifugation. LS means are based off an ANCOVA model which includes treatment group (evoloumab + ezetimibe and ezetimibe alone) and stratification factors as covariates.
Time frame: Baseline and Week 12
Population: Full analysis set; Missing UC LDL-C at Week 12 was imputed using LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Change From Baseline in LDL-C at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe | -17.9 mg/dL | Standard Error 10.4 |
| Evolocumab 280 mg | Change From Baseline in LDL-C at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe | -109.8 mg/dL | Standard Error 11 |
p-value: <195% CI: [-108.7, -75]ANCOVA
Secondary
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12
LS means are based off an ANCOVA model which includes treatment group (3 evolocumab alone dose groups and the ezetimibe group) and stratification factors as covariates.
Time frame: Baseline and Week 12
Population: Full analysis set; missing data at Week 12 were imputed using LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12 | -11.36 percent change | Standard Error 3.16 |
| Evolocumab 280 mg | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12 | -36.46 percent change | Standard Error 3.18 |
| Evolocumab 350 mg | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12 | -38.17 percent change | Standard Error 3.22 |
| Evolocumab 420 mg | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12 | -45.41 percent change | Standard Error 3.19 |
p-value: <0.00195% CI: [-40.57, -27.52]ANCOVA
p-value: <0.00195% CI: [-33.35, -20.27]ANCOVA
p-value: <0.00195% CI: [-31.57, -18.62]ANCOVA
Secondary
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe
LS means are based off an ANCOVA model which includes treatment group (evoloumab + ezetimibe and ezetimibe alone) and stratification factors as covariates.
Time frame: Baseline and Week 12
Population: Full analysis set; missing data at Week 12 were imputed using LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe | -10.74 percent change | Standard Error 3.55 |
| Evolocumab 280 mg | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe | -51.99 percent change | Standard Error 3.76 |
p-value: <0.00195% CI: [-46.99, -35.5]ANCOVA
Secondary
Percent Change From Baseline in Apolipoprotein B at Week 12
LS means are based off an ANCOVA model which includes treatment group (3 evolocumab alone dose groups and the ezetimibe group) and stratification factors as covariates.
Time frame: Baseline and Week 12
Population: Full analysis set; missing Apolipoprotein B at Week 12 was imputed using LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in Apolipoprotein B at Week 12 | -12.20 percent change | Standard Error 3.37 |
| Evolocumab 280 mg | Percent Change From Baseline in Apolipoprotein B at Week 12 | -33.58 percent change | Standard Error 3.39 |
| Evolocumab 350 mg | Percent Change From Baseline in Apolipoprotein B at Week 12 | -34.33 percent change | Standard Error 3.43 |
| Evolocumab 420 mg | Percent Change From Baseline in Apolipoprotein B at Week 12 | -42.07 percent change | Standard Error 3.4 |
p-value: <0.00195% CI: [-36.84, -22.92]ANCOVA
p-value: <0.00195% CI: [-29.1, -15.16]ANCOVA
p-value: <0.00195% CI: [-28.29, -14.48]ANCOVA
Secondary
Percent Change From Baseline in Apolipoprotein B at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe
LS means are based off an ANCOVA model which includes treatment group (evoloumab + ezetimibe and ezetimibe) and stratification factors as covariates.
Time frame: Baseline and Week 12
Population: Full analysis set; missing Apolipoprotein B at Week 12 was imputed using LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in Apolipoprotein B at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe | -10.84 percent change | Standard Error 3.45 |
| Evolocumab 280 mg | Percent Change From Baseline in Apolipoprotein B at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe | -49.06 percent change | Standard Error 3.66 |
p-value: <0.00195% CI: [-43.81, -32.64]ANCOVA
Secondary
Percent Change From Baseline in Non-HDL-C at Week 12
LS means are based off an ANCOVA model which includes treatment group (3 evolocumab alone dose groups and the ezetimibe group) and stratification factors as covariates.
Time frame: Baseline and Week 12
Population: Full analysis set; missing non-HDL-C at Week 12 was imputed using LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in Non-HDL-C at Week 12 | -14.97 percent change | Standard Error 3.54 |
| Evolocumab 280 mg | Percent Change From Baseline in Non-HDL-C at Week 12 | -39.83 percent change | Standard Error 3.56 |
| Evolocumab 350 mg | Percent Change From Baseline in Non-HDL-C at Week 12 | -41.63 percent change | Standard Error 3.61 |
| Evolocumab 420 mg | Percent Change From Baseline in Non-HDL-C at Week 12 | -48.58 percent change | Standard Error 3.58 |
p-value: <0.00195% CI: [-40.93, -26.28]ANCOVA
p-value: <0.00195% CI: [-33.99, -19.32]ANCOVA
p-value: <0.00195% CI: [-32.13, -17.59]ANCOVA
Secondary
Percent Change From Baseline in Non-HDL-C at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe
LS means are based off an ANCOVA model which includes treatment group (evolocumab + ezetimibe and ezetimibe alone) and stratification factors as covariates.
Time frame: Baseline and Week 12
Population: Full analysis set; missing non-HDL-C at Week 12 was imputed using LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in Non-HDL-C at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe | -14.83 percent change | Standard Error 3.59 |
| Evolocumab 280 mg | Percent Change From Baseline in Non-HDL-C at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe | -59.82 percent change | Standard Error 3.81 |
p-value: <0.00195% CI: [-50.81, -39.18]ANCOVA
Secondary
Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12
LS means are based off an ANCOVA model which includes treatment group (3 evolocumab alone dose groups and the ezetimibe group) and stratification factors as covariates.
Time frame: Baseline and Week 12
Population: Full analysis set; missing data at Week 12 were imputed using LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12 | -9.61 percent change | Standard Error 3.2 |
| Evolocumab 280 mg | Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12 | -31.97 percent change | Standard Error 3.22 |
| Evolocumab 350 mg | Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12 | -33.52 percent change | Standard Error 3.26 |
| Evolocumab 420 mg | Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12 | -40.56 percent change | Standard Error 3.23 |
p-value: <0.00195% CI: [-37.56, -24.34]ANCOVA
p-value: <0.00195% CI: [-30.53, -17.29]ANCOVA
p-value: <0.00195% CI: [-28.92, -15.8]ANCOVA
Secondary
Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe
LS means are based off an ANCOVA model which includes treatment group (evoloumab + ezetimibe and ezetimibe alone) and stratification factors as covariates.
Time frame: Baseline and Week 12
Population: Full analysis set; missing data at Week 12 were imputed using LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe | -11.52 percent change | Standard Error 3.61 |
| Evolocumab 280 mg | Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe | -49.44 percent change | Standard Error 3.83 |
p-value: <0.00195% CI: [-43.77, -32.07]ANCOVA