Hyperlipidemia
Conditions
Keywords
High Cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia
Brief summary
The primary objective was to evaluate the effect of 12 weeks of subcutaneous (SC) evolocumab every 2 weeks (Q2W) and monthly (QM), compared with ezetimibe, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic adults unable to tolerate an effective dose of a statin (HMG-CoA (5-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors).
Interventions
BIOLOGICALEvolocumab
Subcutaneous injection
Subcutaneous injection
DRUGEzetimibe
Tablet for oral administration
Tablet for oral administration
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 80 Years
Healthy volunteers
No
Inclusion criteria
* Male or female ≥ 18 to ≤ 80 years of age * Not on a statin or on a low dose statin with stable dose for at least 4 weeks * History of intolerance to at least 2 statins * Subject not at LDL-C goal * Lipid lowering therapy has been stable prior to enrolment for at least 4 weeks. * Fasting triglycerides ≤ 400 mg/dL
Exclusion criteria
* New York Heart Association (NYHA) III or IV heart failure * Uncontrolled cardiac arrhythmia * Uncontrolled hypertension * Type 1 diabetes, poorly controlled type 2 diabetes * Uncontrolled hypothyroidism or hyperthyroidism
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline in LDL-C at Week 12 | Baseline and Week 12 |
| Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L) | Weeks 10 and 12 |
| Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12 | Week 12 |
| Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 |
| Percent Change From Baseline in Non-HDL-C at Week 12 | Baseline and Week 12 |
| Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 |
| Percent Change From Baseline in Apolipoprotein B at Week 12 | Baseline and Week 12 |
| Percent Change From Baseline in the Total Cholesterol/High Density Lipoprotein Cholesterol Ratio at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 |
| Percent Change From Baseline in the Total Cholesterol/High Density Lipoprotein Cholesterol Ratio at Week 12 | Baseline and Week 12 |
| Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 |
| Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 |
| Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 |
| Percent Change From Baseline in Lipoprotein (a) at Week 12 | Baseline and Week 12 |
| Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 |
| Percent Change From Baseline in Triglycerides at Week 12 | Baseline and Week 12 |
| Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 |
| Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12 | Baseline and Week 12 |
| Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 |
| Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at Week 12 | Baseline and Week 12 |
| Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12 | Baseline and Week 12 |
| Change From Baseline in LDL-C at Week 12 | Baseline and Week 12 |
Countries
Australia, Belgium, Canada, Denmark, France, Germany, Hong Kong, Netherlands, Poland, South Africa, Spain, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
Men and women ≥ 18 to ≤ 80 years of age who have tried at least 2 statins and were unable to tolerate any dose or increase in statin dose due to muscle-related side effects were eligible for this study. The first participant was enrolled on 24 January 2013 and the last participant enrolled on 29 August 2013.
Pre-assignment details
Participants received subcutaneous placebo corresponding to the once monthly dose volume during a 6-week screening period. Those who completed the screening period and met final eligibility criteria were randomized 1:1:2:2 into 4 treatment groups. Randomization was stratified by low-density lipoprotein cholesterol (LDL-C) level and statin use.
Participants by arm
| Arm | Count |
|---|---|
| Ezetimibe (Q2W) Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. | 51 |
| Ezetimibe (QM) Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. | 51 |
| Evolocumab Q2W Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. | 103 |
| Evolocumab QM Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks. | 102 |
| Total | 307 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Decision by sponsor | 5 | 0 | 8 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Evolocumab QM | Evolocumab Q2W | Ezetimibe (QM) | Ezetimibe (Q2W) |
|---|---|---|---|---|---|
| Age, Continuous | 61.5 years STANDARD_DEVIATION 9.8 | 62.9 years STANDARD_DEVIATION 10.2 | 60.5 years STANDARD_DEVIATION 9.7 | 60.2 years STANDARD_DEVIATION 8.7 | 61.7 years STANDARD_DEVIATION 10.1 |
| Apolipoprotein B/Apolipoprotein A1 Ratio | 0.952 ratio STANDARD_DEVIATION 0.298 | 0.901 ratio STANDARD_DEVIATION 0.283 | 0.980 ratio STANDARD_DEVIATION 0.318 | 1.005 ratio STANDARD_DEVIATION 0.294 | 0.943 ratio STANDARD_DEVIATION 0.282 |
| Apolipoprotein B Concentration | 137.8 mg/dL STANDARD_DEVIATION 32.8 | 133.1 mg/dL STANDARD_DEVIATION 32.2 | 140.2 mg/dL STANDARD_DEVIATION 32.1 | 140.0 mg/dL STANDARD_DEVIATION 31.1 | 140.0 mg/dL STANDARD_DEVIATION 37 |
| High-Density Lipoprotein Cholesterol (HDL-C) | 51.8 mg/dL STANDARD_DEVIATION 15.9 | 54.0 mg/dL STANDARD_DEVIATION 16 | 51.1 mg/dL STANDARD_DEVIATION 16.4 | 48.0 mg/dL STANDARD_DEVIATION 11 | 52.4 mg/dL STANDARD_DEVIATION 18.3 |
| LDL-C Concentration | 193.1 mg/dL STANDARD_DEVIATION 58.5 | 192.2 mg/dL STANDARD_DEVIATION 61.2 | 192.0 mg/dL STANDARD_DEVIATION 57 | 195.2 mg/dL STANDARD_DEVIATION 51.8 | 194.7 mg/dL STANDARD_DEVIATION 63.8 |
| Lipoprotein(a) Concentration | 76.2 nmol/L STANDARD_DEVIATION 91.9 | 70.9 nmol/L STANDARD_DEVIATION 99.9 | 66.2 nmol/L STANDARD_DEVIATION 72.5 | 76.6 nmol/L STANDARD_DEVIATION 96.7 | 106.3 nmol/L STANDARD_DEVIATION 101 |
| Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Concentration | 227.4 mg/dL STANDARD_DEVIATION 60.4 | 222.1 mg/dL STANDARD_DEVIATION 63.2 | 227.9 mg/dL STANDARD_DEVIATION 56.6 | 232.9 mg/dL STANDARD_DEVIATION 57 | 231.4 mg/dL STANDARD_DEVIATION 66 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 10 participants | 1 participants | 5 participants | 3 participants | 1 participants |
| Race/Ethnicity, Customized Black or African American | 7 participants | 3 participants | 3 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 7 participants | 1 participants | 3 participants | 2 participants | 1 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 participants | 0 participants | 1 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 300 participants | 101 participants | 100 participants | 49 participants | 50 participants |
| Race/Ethnicity, Customized Other | 2 participants | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 287 participants | 98 participants | 94 participants | 46 participants | 49 participants |
| Sex: Female, Male Female | 141 Participants | 46 Participants | 46 Participants | 22 Participants | 27 Participants |
| Sex: Female, Male Male | 166 Participants | 56 Participants | 57 Participants | 29 Participants | 24 Participants |
| Stratification Factor: Baseline Statin Use No | 249 participants | 82 participants | 84 participants | 42 participants | 41 participants |
| Stratification Factor: Baseline Statin Use Yes | 58 participants | 20 participants | 19 participants | 9 participants | 10 participants |
| Stratification Factor: Low-density Lipoprotein Cholesterol (LDL-C) Level < 180 mg/dL | 156 participants | 52 participants | 52 participants | 26 participants | 26 participants |
| Stratification Factor: Low-density Lipoprotein Cholesterol (LDL-C) Level ≥ 180 mg/dL | 151 participants | 50 participants | 51 participants | 25 participants | 25 participants |
| Total Cholesterol/High-Density Lipoprotein Cholesterol Ratio | 5.827 ratio STANDARD_DEVIATION 1.956 | 5.506 ratio STANDARD_DEVIATION 1.925 | 5.912 ratio STANDARD_DEVIATION 1.929 | 6.137 ratio STANDARD_DEVIATION 1.787 | 5.989 ratio STANDARD_DEVIATION 2.19 |
| Triglyceride Concentration | 171.5 mg/dL STANDARD_DEVIATION 76.3 | 149.3 mg/dL STANDARD_DEVIATION 63.1 | 179.8 mg/dL STANDARD_DEVIATION 80 | 187.0 mg/dL STANDARD_DEVIATION 81.5 | 183.4 mg/dL STANDARD_DEVIATION 79.8 |
| Very Low-density Lipoprotein Cholesterol (VLDL-C) Concentration | 34.0 mg/dL STANDARD_DEVIATION 14.6 | 29.9 mg/dL STANDARD_DEVIATION 12.6 | 35.2 mg/dL STANDARD_DEVIATION 14.5 | 37.1 mg/dL STANDARD_DEVIATION 15.8 | 36.7 mg/dL STANDARD_DEVIATION 16 |
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 | 20 / 51 | 29 / 51 | 28 / 103 | 42 / 102 |
| serious Total, serious adverse events | 1 / 51 | 3 / 51 | 5 / 103 | 1 / 102 |
Outcome results
Primary
Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Population: Full analysis set with available data (no imputation was performed).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe (Q2W) | Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -19.21 percent change | Standard Error 2.4 |
| Ezetimibe (QM) | Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -16.62 percent change | Standard Error 2.03 |
| Evolocumab Q2W | Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -56.11 percent change | Standard Error 1.83 |
| Evolocumab QM | Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -55.31 percent change | Standard Error 1.53 |
Comparison: The null hypothesis was that there is no mean difference in the percent change from Baseline in the average value of LDL-C at Weeks 10 and 12 between evolocumab and ezetimibe, and the alternative hypothesis is that a mean difference does exist.p-value: <0.00195% CI: [-42.26, -31.55]Repeated measures linear effects model
Comparison: The null hypothesis was that there is no mean difference in the percent change from Baseline in the average value of LDL-C at Weeks 10 and 12 between evolocumab and ezetimibe, and the alternative hypothesis is that a mean difference does exist.p-value: <0.00195% CI: [-43.06, -34.22]Repeated measures linear effects model
Primary
Percent Change From Baseline in LDL-C at Week 12
Time frame: Baseline and Week 12
Population: Full analysis set (all randomized participants who received at least 1 dose of investigational product (subcutaneously or orally)) with available data (no imputation was performed).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe (Q2W) | Percent Change From Baseline in LDL-C at Week 12 | -18.08 percent change | Standard Error 2.52 |
| Ezetimibe (QM) | Percent Change From Baseline in LDL-C at Week 12 | -15.05 percent change | Standard Error 2.13 |
| Evolocumab Q2W | Percent Change From Baseline in LDL-C at Week 12 | -56.14 percent change | Standard Error 1.91 |
| Evolocumab QM | Percent Change From Baseline in LDL-C at Week 12 | -52.60 percent change | Standard Error 1.58 |
Comparison: The null hypothesis was that there is no mean difference in the percent change from Baseline at Week 12 in LDL-C between evolocumab and ezetimibe, and the alternative hypothesis is that a mean difference does exist.p-value: <0.00195% CI: [-43.73, -32.99]Repeated measures linear effects model
Comparison: The null hypothesis was that there is no mean difference in the percent change from baseline at Week 12 in LDL-C between evolocumab and ezetimibe, and the alternative hypothesis is that a mean difference does exist.p-value: <0.00195% CI: [-42.16, -32.94]Repeated measures linear effects model
Secondary
Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe (Q2W) | Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -39.1 mg/dL | Standard Error 5.1 |
| Ezetimibe (QM) | Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -33.0 mg/dL | Standard Error 4.5 |
| Evolocumab Q2W | Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -105.4 mg/dL | Standard Error 3.9 |
| Evolocumab QM | Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -103.6 mg/dL | Standard Error 3.4 |
p-value: <0.00195% CI: [-77.9, -54.7]Repeated measures linear effects model
p-value: <0.00195% CI: [-80.5, -60.7]Repeated measures linear effects model
Secondary
Change From Baseline in LDL-C at Week 12
Time frame: Baseline and Week 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe (Q2W) | Change From Baseline in LDL-C at Week 12 | -36.2 mg/dL | Standard Error 5.4 |
| Ezetimibe (QM) | Change From Baseline in LDL-C at Week 12 | -30.2 mg/dL | Standard Error 4.7 |
| Evolocumab Q2W | Change From Baseline in LDL-C at Week 12 | -106.0 mg/dL | Standard Error 4.1 |
| Evolocumab QM | Change From Baseline in LDL-C at Week 12 | -99.0 mg/dL | Standard Error 3.5 |
p-value: <0.00195% CI: [-82, -57.5]Repeated measures linear effects model
p-value: <0.00195% CI: [-79.2, -58.4]Repeated measures linear effects model
Secondary
Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12
Time frame: Week 12
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ezetimibe (Q2W) | Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12 | 2.0 percentage of participants |
| Ezetimibe (QM) | Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12 | 0.0 percentage of participants |
| Evolocumab Q2W | Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12 | 50.0 percentage of participants |
| Evolocumab QM | Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12 | 37.5 percentage of participants |
p-value: <0.00195% CI: [35, 57.8]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [25.5, 47.5]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L)
Time frame: Weeks 10 and 12
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ezetimibe (Q2W) | Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L) | 2.0 percentage of participants |
| Ezetimibe (QM) | Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L) | 0.0 percentage of participants |
| Evolocumab Q2W | Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L) | 45.5 percentage of participants |
| Evolocumab QM | Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L) | 42.0 percentage of participants |
p-value: <0.00195% CI: [30.9, 53.4]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [30.3, 51.8]Cochran-Mantel-Haenszel
Secondary
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe (Q2W) | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12 | -13.00 percent change | Standard Error 2.27 |
| Ezetimibe (QM) | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12 | -11.94 percent change | Standard Error 2.56 |
| Evolocumab Q2W | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12 | -47.86 percent change | Standard Error 1.77 |
| Evolocumab QM | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12 | -48.31 percent change | Standard Error 1.92 |
p-value: <0.00195% CI: [-39.84, -29.88]Repeated measures linear effects model
p-value: <0.00195% CI: [-41.73, -31.01]Repeated measures linear effects model
Secondary
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12
Time frame: Baseline and Week 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe (Q2W) | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12 | -13.14 percent change | Standard Error 2.47 |
| Ezetimibe (QM) | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12 | -11.37 percent change | Standard Error 2.71 |
| Evolocumab Q2W | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12 | -47.66 percent change | Standard Error 1.9 |
| Evolocumab QM | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12 | -45.51 percent change | Standard Error 2.01 |
p-value: <0.00195% CI: [-40.05, -29]Repeated measures linear effects model
p-value: <0.00195% CI: [-39.87, -28.39]Repeated measures linear effects model
Secondary
Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Population: Full anlaysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe (Q2W) | Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 | -13.67 percent change | Standard Error 2.15 |
| Ezetimibe (QM) | Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 | -11.02 percent change | Standard Error 2.21 |
| Evolocumab Q2W | Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 | -45.88 percent change | Standard Error 1.68 |
| Evolocumab QM | Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 | -46.01 percent change | Standard Error 1.65 |
p-value: <0.00195% CI: [-36.92, -27.49]Repeated measures linear effects model
p-value: <0.00195% CI: [-39.59, -30.39]Repeated measures linear effects model
Secondary
Percent Change From Baseline in Apolipoprotein B at Week 12
Time frame: Baseline and Week 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe (Q2W) | Percent Change From Baseline in Apolipoprotein B at Week 12 | -12.95 percent change | Standard Error 2.32 |
| Ezetimibe (QM) | Percent Change From Baseline in Apolipoprotein B at Week 12 | -9.97 percent change | Standard Error 2.34 |
| Evolocumab Q2W | Percent Change From Baseline in Apolipoprotein B at Week 12 | -45.81 percent change | Standard Error 1.79 |
| Evolocumab QM | Percent Change From Baseline in Apolipoprotein B at Week 12 | -43.07 percent change | Standard Error 1.73 |
p-value: <0.00195% CI: [-38.04, -27.68]Repeated measures linear effects model
p-value: <0.00195% CI: [-38.04, -28.17]Repeated measures linear effects model
Secondary
Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe (Q2W) | Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at the Mean of Weeks 10 and 12 | 0.33 percent change | Standard Error 1.98 |
| Ezetimibe (QM) | Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at the Mean of Weeks 10 and 12 | 1.44 percent change | Standard Error 2.03 |
| Evolocumab Q2W | Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at the Mean of Weeks 10 and 12 | 5.48 percent change | Standard Error 1.51 |
| Evolocumab QM | Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at the Mean of Weeks 10 and 12 | 7.18 percent change | Standard Error 1.51 |
p-value: 0.06895% CI: [0.74, 9.56]Repeated measures linear effects model
p-value: 0.1395% CI: [1.23, 10.24]Repeated measures linear effects model
Secondary
Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12
Time frame: Baseline and Week 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe (Q2W) | Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12 | 1.77 percent change | Standard Error 2.22 |
| Ezetimibe (QM) | Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12 | 1.64 percent change | Standard Error 2.22 |
| Evolocumab Q2W | Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12 | 5.34 percent change | Standard Error 1.67 |
| Evolocumab QM | Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12 | 6.47 percent change | Standard Error 1.63 |
p-value: 0.06895% CI: [-1.49, 8.63]Repeated measures linear effects model
p-value: 0.1395% CI: [-0.16, 9.81]Repeated measures linear effects model
Secondary
Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe (Q2W) | Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12 | -2.30 percent change | Standard Error 3.36 |
| Ezetimibe (QM) | Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12 | 1.55 percent change | Standard Error 4.01 |
| Evolocumab Q2W | Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12 | -26.20 percent change | Standard Error 2.64 |
| Evolocumab QM | Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12 | -23.72 percent change | Standard Error 2.97 |
p-value: <0.00195% CI: [-31.27, -16.54]Repeated measures linear effects model
p-value: <0.00195% CI: [-33.75, -16.77]Repeated measures linear effects model
Secondary
Percent Change From Baseline in Lipoprotein (a) at Week 12
Time frame: Baseline and Week 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe (Q2W) | Percent Change From Baseline in Lipoprotein (a) at Week 12 | -1.74 percent change | Standard Error 3.58 |
| Ezetimibe (QM) | Percent Change From Baseline in Lipoprotein (a) at Week 12 | 5.81 percent change | Standard Error 5.1 |
| Evolocumab Q2W | Percent Change From Baseline in Lipoprotein (a) at Week 12 | -27.03 percent change | Standard Error 2.78 |
| Evolocumab QM | Percent Change From Baseline in Lipoprotein (a) at Week 12 | -22.07 percent change | Standard Error 3.66 |
p-value: <0.00195% CI: [-33.26, -17.33]Repeated measures linear effects model
p-value: <0.00195% CI: [-39.21, -16.56]Repeated measures linear effects model
Secondary
Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe (Q2W) | Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12 | -17.18 percent change | Standard Error 2.15 |
| Ezetimibe (QM) | Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12 | -14.54 percent change | Standard Error 1.86 |
| Evolocumab Q2W | Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12 | -48.72 percent change | Standard Error 1.64 |
| Evolocumab QM | Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12 | -49.13 percent change | Standard Error 1.4 |
p-value: <0.00195% CI: [-36.34, -26.73]Repeated measures linear effects model
p-value: <0.00195% CI: [-38.63, -30.54]Repeated measures linear effects model
Secondary
Percent Change From Baseline in Non-HDL-C at Week 12
Time frame: Baseline and Week 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe (Q2W) | Percent Change From Baseline in Non-HDL-C at Week 12 | -16.53 percent change | Standard Error 2.3 |
| Ezetimibe (QM) | Percent Change From Baseline in Non-HDL-C at Week 12 | -13.16 percent change | Standard Error 1.93 |
| Evolocumab Q2W | Percent Change From Baseline in Non-HDL-C at Week 12 | -48.62 percent change | Standard Error 1.74 |
| Evolocumab QM | Percent Change From Baseline in Non-HDL-C at Week 12 | -46.15 percent change | Standard Error 1.43 |
p-value: <0.00195% CI: [-37.28, -26.9]Repeated measures linear effects model
p-value: <0.00195% CI: [-37.19, -28.79]Repeated measures linear effects model
Secondary
Percent Change From Baseline in the Total Cholesterol/High Density Lipoprotein Cholesterol Ratio at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe (Q2W) | Percent Change From Baseline in the Total Cholesterol/High Density Lipoprotein Cholesterol Ratio at the Mean of Weeks 10 and 12 | -13.44 percent change | Standard Error 2.14 |
| Ezetimibe (QM) | Percent Change From Baseline in the Total Cholesterol/High Density Lipoprotein Cholesterol Ratio at the Mean of Weeks 10 and 12 | -11.20 percent change | Standard Error 2.16 |
| Evolocumab Q2W | Percent Change From Baseline in the Total Cholesterol/High Density Lipoprotein Cholesterol Ratio at the Mean of Weeks 10 and 12 | -40.83 percent change | Standard Error 1.65 |
| Evolocumab QM | Percent Change From Baseline in the Total Cholesterol/High Density Lipoprotein Cholesterol Ratio at the Mean of Weeks 10 and 12 | -41.14 percent change | Standard Error 1.62 |
p-value: <0.00195% CI: [-32.11, -22.67]Repeated measures linear effects model
p-value: <0.00195% CI: [-34.72, -25.17]Repeated measures linear effects model
Secondary
Percent Change From Baseline in the Total Cholesterol/High Density Lipoprotein Cholesterol Ratio at Week 12
Time frame: Baseline and Week 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe (Q2W) | Percent Change From Baseline in the Total Cholesterol/High Density Lipoprotein Cholesterol Ratio at Week 12 | -14.13 percent change | Standard Error 2.3 |
| Ezetimibe (QM) | Percent Change From Baseline in the Total Cholesterol/High Density Lipoprotein Cholesterol Ratio at Week 12 | -9.92 percent change | Standard Error 2.34 |
| Evolocumab Q2W | Percent Change From Baseline in the Total Cholesterol/High Density Lipoprotein Cholesterol Ratio at Week 12 | -40.42 percent change | Standard Error 1.75 |
| Evolocumab QM | Percent Change From Baseline in the Total Cholesterol/High Density Lipoprotein Cholesterol Ratio at Week 12 | -38.57 percent change | Standard Error 1.73 |
p-value: <0.00195% CI: [-31.42, -21.15]Repeated measures linear effects model
p-value: <0.00195% CI: [-33.88, -23.43]Repeated measures linear effects model
Secondary
Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe (Q2W) | Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 | -3.74 percent change | Standard Error 3.88 |
| Ezetimibe (QM) | Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 | -0.32 percent change | Standard Error 4.65 |
| Evolocumab Q2W | Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 | -6.32 percent change | Standard Error 2.94 |
| Evolocumab QM | Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 | -6.73 percent change | Standard Error 3.44 |
p-value: 0.9795% CI: [-11.38, 6.2]Repeated measures linear effects model
p-value: 0.3395% CI: [-16.55, 3.71]Repeated measures linear effects model
Secondary
Percent Change From Baseline in Triglycerides at Week 12
Time frame: Baseline and Week 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe (Q2W) | Percent Change From Baseline in Triglycerides at Week 12 | -5.47 percent change | Standard Error 4.25 |
| Ezetimibe (QM) | Percent Change From Baseline in Triglycerides at Week 12 | 2.16 percent change | Standard Error 5.52 |
| Evolocumab Q2W | Percent Change From Baseline in Triglycerides at Week 12 | -3.88 percent change | Standard Error 3.18 |
| Evolocumab QM | Percent Change From Baseline in Triglycerides at Week 12 | -2.53 percent change | Standard Error 3.98 |
p-value: 0.9795% CI: [-8.14, 11.31]Repeated measures linear effects model
p-value: 0.3395% CI: [-17.04, 7.67]Repeated measures linear effects model
Secondary
Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe (Q2W) | Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at the Mean of Weeks 10 and 12 | -5.76 percent change | Standard Error 3.8 |
| Ezetimibe (QM) | Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at the Mean of Weeks 10 and 12 | -2.93 percent change | Standard Error 4.41 |
| Evolocumab Q2W | Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at the Mean of Weeks 10 and 12 | -7.60 percent change | Standard Error 2.89 |
| Evolocumab QM | Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at the Mean of Weeks 10 and 12 | -6.46 percent change | Standard Error 3.21 |
p-value: 0.9795% CI: [-10.43, 6.75]Repeated measures linear effects model
p-value: 0.3395% CI: [-13.12, 6.06]Repeated measures linear effects model
Secondary
Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at Week 12
Time frame: Baseline and Week 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe (Q2W) | Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at Week 12 | -5.49 percent change | Standard Error 4.05 |
| Ezetimibe (QM) | Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at Week 12 | -2.25 percent change | Standard Error 5.11 |
| Evolocumab Q2W | Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at Week 12 | -6.16 percent change | Standard Error 3.08 |
| Evolocumab QM | Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at Week 12 | -2.18 percent change | Standard Error 3.6 |
p-value: 0.9795% CI: [-9.96, 8.61]Repeated measures linear effects model
p-value: 0.3395% CI: [-11.24, 11.39]Repeated measures linear effects model