CompletedNCT01763827MENDEL-2Updated Nov 8, 2022Results posted

Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy for Easing Lipid Levels-2

A Phase 3 interventional study of Evolocumab and Ezetimibe in Hyperlipidemia, sponsored by Amgen. Completed at 83 sites in 10 countries. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2022-11-08.

Sponsored by Amgen · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 615
Allocation: Randomized
Ages: 18 Years to 80 Years
Sex: All

Study summary

The primary objective was to evaluate the effect of 12 weeks of evolocumab subcutaneous (SC) monotherapy every 2 weeks (Q2W) and monthly (QM), compared with placebo and ezetimibe, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in adults with a 10-year Framingham risk score of 10% or less.

Conditions studied

Hyperlipidemia

Browse trials for

Hyperlipidemias 821

Keywords

High cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia

In context

Hyperlipidemias

821 studies on the registry are indexed under Hyperlipidemias; 105 are open to participants now.

This study's enrollment of 615 is above the median of 87 across 691 interventional studies indexed under Hyperlipidemias.

Browse Hyperlipidemias studies →

Lead sponsor

Amgen is the lead sponsor of 1,016 studies on the registry; 50 are open to participants now.

Of its 245 completed or terminated interventional studies of FDA-regulated products, 159 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 80 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Male or female ≥ 18 to ≤ 80 years of age
National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) Framingham risk score of 10% or less
Fasting LDL-C ≥ 100 mg/dL (2.6 mmol/L) and \<190 mg/dL
Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L)

Exclusion criteria

Exclusion Criteria:

History of coronary heart disease
New York Heart Association (NYHA) III or IV heart failure
Uncontrolled cardiac arrhythmia
Uncontrolled hypertension
Diabetes mellitus (Type 1 diabetes, poorly controlled type 2 diabetes)
Uncontrolled hypothyroidism or hyperthyroidism

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 615 participants (actual)

Study arms

Placebo comparator
Placebo Q2W
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.
Biological: Placebo to Evolocumab · Other: Placebo to Ezetimibe
Placebo comparator
Placebo QM
Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
Biological: Placebo to Evolocumab · Other: Placebo to Ezetimibe
Active comparator
Ezetimibe (Q2W)
Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
Drug: Ezetimibe · Biological: Placebo to Evolocumab
Active comparator
Ezetimibe (QM)
Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
Drug: Ezetimibe · Biological: Placebo to Evolocumab
Experimental
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.
Biological: Evolocumab · Other: Placebo to Ezetimibe
Experimental
Evolocumab QM
Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
Biological: Evolocumab · Other: Placebo to Ezetimibe

Interventions

BiologicalEvolocumab
Administered by subcutaneous injection
Also known as: AMG 145, Repatha
DrugEzetimibe
Administered orally once a day
Also known as: Zetia
BiologicalPlacebo to Evolocumab
Administered by subcutaneous injection
OtherPlacebo to Ezetimibe
Administered orally once daily

What researchers measure

Primary outcomes

Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12

Secondary outcomes

Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Change From Baseline in LDL-C at Week 12
Time frame: Baseline and Week 12
Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL
Time frame: Weeks 10 and 12
Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12
Time frame: Week 12
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Percent Change From Baseline in Non-HDL-C at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Percent Change From Baseline in Apolipoprotein B at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-cholesterol Ratio at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-cholesterol Ratio at Week 12
Time frame: Baseline and Week 12
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
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Percent Change From Baseline in Lipoprotein (a) at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Percent Change From Baseline in Triglycerides at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in Very Low Density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Percent Change From Baseline in VLDL-C at Week 12
Time frame: Baseline and Week 12
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
Percent Change From Baseline in HDL-C at Week 12
Time frame: Baseline and Week 12

Results

Posted Dec 30, 2015

Participant flow

Men and women ≥ 18 to ≤ 80 years of age with fasting low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL and \< 190 mg/dL and fasting triglycerides ≤ 400 mg/dL with a 10-year Framingham Risk Score of 10% or less were eligible for this study. The first participant was enrolled on 21 January 2013 and the last participant was enrolled 29 July 2013.

Participant flow — Overall Study
Milestone	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM
Started	77	78	77	77	153	153
Received at least 1 dose of study drug	76	78	77	77	153	153
Completed	74	77	73	76	147	151
Not completed	3	1	4	1	6	2
Withdrew: Withdrawal by subject	1	0	0	0	2	0
Withdrew: Decision by sponsor	2	0	3	0	2	1
Withdrew: Lost to follow-up	0	1	1	1	2	1

Outcome measures

PrimaryPercent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12

Time frame:: Baseline and Week 12
Reported as:: Least squares mean · percent change

Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12
percent change	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12	0.10 ± 1.67	-1.34 ± 1.54	-17.75 ± 1.67	-18.57 ± 1.56	-57.04 ± 1.23	-56.12 ± 1.12

Statistical analysis

Placebo Q2W vs Evolocumab Q2W · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -57.14 · 95% CI -61.14 to -53.14Placebo is the reference
Placebo QM vs Evolocumab QM · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -54.78 · 95% CI -58.46 to -51.10Placebo is the reference
Ezetimibe (Q2W) vs Evolocumab Q2W · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -39.29 · 95% CI -43.28 to -35.31Ezetimibe is the reference
Ezetimibe (QM) vs Evolocumab QM · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -37.55 · 95% CI -41.24 to -33.86Ezetimibe is the reference

PrimaryPercent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12

Time frame:: Baseline and Weeks 10 and 12
Reported as:: Least squares mean · percent change

Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
percent change	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM
Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12	-0.43 ± 1.45	-1.41 ± 1.37	-17.52 ± 1.46	-19.12 ± 1.39	-56.93 ± 1.07	-58.81 ± 1.00

Statistical analysis

Placebo Q2W vs Evolocumab Q2W · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -56.50 · 95% CI -59.95 to -53.04Placebo is the reference
Placebo QM vs Evolocumab QM · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -57.40 · 95% CI -60.66 to -54.14Placebo is the reference
Ezetimibe (Q2W) vs Evolocumab Q2W · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -39.41 · 95% CI -42.87 to -35.94Ezetimibe is the reference
Ezetimibe (QM) vs Evolocumab QM · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -36.69 · 95% CI -42.97 to -36.42Ezetimibe is the reference

SecondaryChange From Baseline in LDL-C at the Mean of Weeks 10 and 12

Time frame:: Baseline and Weeks 10 and 12
Reported as:: Least squares mean · mg/dL

Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
mg/dL	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM
Change From Baseline in LDL-C at the Mean of Weeks 10 and 12	1.2 ± 2.3	0.0 ± 2.1	-23.1 ± 2.3	-25.9 ± 2.1	-78.4 ± 1.7	-81.9 ± 1.5

Statistical analysis

Placebo Q2W vs Evolocumab Q2W · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -79.6 · 95% CI -85.0 to -74.2Placebo is the reference
Placebo QM vs Evolocumab QM · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -81.9 · 95% CI -87.0 to -76.9Placebo is the reference
Ezetimibe (Q2W) vs Evolocumab Q2W · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -55.3 · 95% CI -60.7 to -49.9Ezetimibe is the reference
Ezetimibe (QM) vs Evolocumab QM · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -56.1 · 95% CI -61.1 to -51.0Ezetimibe is the reference

SecondaryChange From Baseline in LDL-C at Week 12

Time frame:: Baseline and Week 12
Reported as:: Least squares mean · mg/dL

Change From Baseline in LDL-C at Week 12
mg/dL	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM
Change From Baseline in LDL-C at Week 12	1.9 ± 2.5	-0.1 ± 2.4	-23.4 ± 2.5	-25.0 ± 2.4	-78.4 ± 1.9	-77.9 ± 1.7

Statistical analysis

Placebo Q2W vs Evolocumab Q2W · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -80.4 · 95% CI -86.4 to -74.3Placebo is the reference
Placebo QM vs Evolocumab QM · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -77.8 · 95% CI -83.4 to -72.2Placebo is the reference
Ezetimibe (Q2W) vs Evolocumab Q2W · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -55.0 · 95% CI -61.1 to -49.0Ezetimibe was the reference
Ezetimibe (QM) vs Evolocumab QM · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -52.9 · 95% CI -58.5 to -47.3Ezetimibe was the reference

SecondaryPercentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL

Time frame:: Weeks 10 and 12
Reported as:: Number · percentage of participants

Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL
percentage of participants	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM
Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL	0.0 (0.0 to 4.8)	0.0 (0.0 to 4.9)	1.3 (0.2 to 7.2)	2.8 (0.8 to 9.6)	73.6 (65.7 to 80.2)	71.3 (63.6 to 78.0)

Statistical analysis

Placebo Q2W vs Evolocumab Q2W · Cochran-Mantel-Haenszel · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Treatment difference: 73.6 · 95% CI 64.4 to 80.2Based on CMH test stratified by Baseline LDL-C level. For testing, non-achievement was imputed for participants with a missing value.
Placebo QM vs Evolocumab QM · Cochran-Mantel-Haenszel · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Treatment difference: 71.3 · 95% CI 62.2 to 78.0Based on CMH test stratified by Baseline LDL-C level. For testing, non-achievement was imputed for participants with a missing value.
Ezetimibe (Q2W) vs Evolocumab Q2W · Cochran-Mantel-Haenszel · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Treatment difference: 72.2 · 95% CI 62.4 to 78.9Based on CMH test stratified by Baseline LDL-C level. For testing, non-achievement was imputed for participants with a missing value.
Ezetimibe (QM) vs Evolocumab QM · Cochran-Mantel-Haenszel · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Treatment difference: 68.6 · 95% CI 58.3 to 75.5Based on CMH test stratified by Baseline LDL-C level. For testing, non-achievement was imputed for participants with a missing value.

SecondaryPercentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12

Time frame:: Week 12
Reported as:: Number · percentage of participants

Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12
percentage of participants	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM
Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12	1.4 (0.3 to 7.8)	0.0 (0.0 to 5.2)	1.4 (0.3 to 7.7)	1.4 (0.3 to 7.8)	72.9 (64.8 to 79.8)	65.4 (57.1 to 72.9)

Statistical analysis

Placebo Q2W vs Evolocumab Q2W · Cochran-Mantel-Haenszel · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Treatment difference: 71.5 · 95% CI 61.2 to 78.4Based on CMH test stratified by Baseline LDL-C level. For testing, non-achievement was imputed for participants with a missing value.
Placebo QM vs Evolocumab QM · Cochran-Mantel-Haenszel · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Treatment difference: 65.4 · 95% CI 55.6 to 72.9Based on CMH test stratified by Baseline LDL-C level. For testing, non-achievement was imputed for participants with a missing value.
Ezetimibe (Q2W) vs Evolocumab Q2W · Cochran-Mantel-Haenszel · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Treatment difference: 71.5 · 95% CI 61.3 to 78.4Based on CMH test stratified by Baseline LDL-C level. For testing, non-achievement was imputed for participants with a missing value.
Ezetimibe (QM) vs Evolocumab QM · Cochran-Mantel-Haenszel · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Treatment difference: 64.0 · 95% CI 53.5 to 71.6Based on CMH test stratified by Baseline LDL-C level. For testing, non-achievement was imputed for participants with a missing value.

SecondaryPercent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 10 and 12

Time frame:: Baseline and Weeks 10 and 12
Reported as:: Least squares mean · percent change

Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 10 and 12
percent change	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 10 and 12	-1.41 ± 1.34	1.32 ± 1.24	-14.64 ± 1.35	-16.48 ± 1.25	-50.22 ± 0.99	-51.96 ± 0.90

Statistical analysis

Placebo Q2W vs Evolocumab Q2W · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -48.81 · 95% CI -52.01 to -45.61Placebo is the reference
Placebo QM vs Evolocumab QM · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -53.28 · 95% CI -56.23 to -50.33Placebo is the reference
Ezetimibe (Q2W) vs Evolocumab Q2W · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -35.58 · 95% CI -38.79 to -32.38Ezetimibe is the reference
Ezetimibe (QM) vs Evolocumab QM · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -35.49 · 95% CI -38.44 to -32.53Ezetimibe is the reference

SecondaryPercent Change From Baseline in Non-HDL-C at Week 12

Time frame:: Baseline and Week 12
Reported as:: Least squares mean · percent change

Percent Change From Baseline in Non-HDL-C at Week 12
percent change	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM
Percent Change From Baseline in Non-HDL-C at Week 12	-0.31 ± 1.48	1.51 ± 1.38	-14.89 ± 1.47	-16.48 ± 1.39	-50.12 ± 1.08	-49.68 ± 1.01

Statistical analysis

Placebo Q2W vs Evolocumab Q2W · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -49.81 · 95% CI -53.34 to -46.27Placebo is the reference
Placebo QM vs Evolocumab QM · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -51.19 · 95% CI -54.49 to -47.90Placebo is the reference
Ezetimibe (Q2W) vs Evolocumab Q2W · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -35.23 · 95% CI -38.74 to -31.71Ezetimibe is the reference
Ezetimibe (QM) vs Evolocumab QM · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -33.21 · 95% CI -36.51 to -29.90Ezetimibe is the reference

SecondaryPercent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12

Time frame:: Baseline and Weeks 10 and 12
Reported as:: Least squares mean · percent change

Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12
percent change	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM
Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12	0.05 ± 1.51	1.54 ± 1.41	-13.47 ± 1.52	-14.75 ± 1.43	-47.04 ± 1.12	-49.39 ± 1.03

Statistical analysis

Placebo Q2W vs Evolocumab Q2W · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -47.09 · 95% CI -50.67 to -43.51Placebo is the reference
Placebo QM vs Evolocumab QM · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -50.93 · 95% CI -54.27 to -47.59Placebo is the reference
Ezetimibe (Q2W) vs Evolocumab Q2W · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -33.57 · 95% CI -37.15 to -29.99Ezetimibe is the reference
Ezetimibe (QM) vs Evolocumab QM · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -34.64 · 95% CI -37.99 to -31.28Ezetimibe is the reference

SecondaryPercent Change From Baseline in Apolipoprotein B at Week 12

Time frame:: Baseline and Week 12
Reported as:: Least squares mean · percent change

Percent Change From Baseline in Apolipoprotein B at Week 12
percent change	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM
Percent Change From Baseline in Apolipoprotein B at Week 12	0.59 ± 1.58	1.84 ± 1.53	-13.17 ± 1.58	-14.02 ± 1.54	-47.21 ± 1.17	-46.59 ± 1.12

Statistical analysis

Placebo Q2W vs Evolocumab Q2W · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -47.81 · 95% CI -51.56 to -44.05Placebo is the reference
Placebo QM vs Evolocumab QM · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -48.43 · 95% CI -52.07 to -44.79Placebo is the reference
Ezetimibe (Q2W) vs Evolocumab Q2W · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -34.04 · 95% CI -37.78 to -30.30Ezetimibe is the reference
Ezetimibe (QM) vs Evolocumab QM · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -32.57 · 95% CI -36.21 to -28.92Ezetimibe is the reference

SecondaryPercent Change From Baseline in Total Cholesterol/High Density Lipoprotein-cholesterol Ratio at the Mean of Weeks 10 and 12

Time frame:: Baseline and Weeks 10 and 12
Reported as:: Least squares mean · percent change

Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-cholesterol Ratio at the Mean of Weeks 10 and 12
percent change	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM
Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-cholesterol Ratio at the Mean of Weeks 10 and 12	0.44 ± 1.29	6.42 ± 1.50	-9.14 ± 1.29	-11.90 ± 1.51	-38.49 ± 0.95	-39.41 ± 1.08

Statistical analysis

Placebo Q2W vs Evolocumab Q2W · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -38.93 · 95% CI -42.00 to -35.86Placebo is the reference
Placebo QM vs Evolocumab QM · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -45.83 · 95% CI -49.39 to -42.27Placebo is the reference
Ezetimibe (Q2W) vs Evolocumab Q2W · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -29.36 · 95% CI -32.43 to -26.28Ezetimibe is the reference
Ezetimibe (QM) vs Evolocumab QM · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -27.51 · 95% CI -31.08 to -23.94Ezetimibe is the reference

SecondaryPercent Change From Baseline in Total Cholesterol/High Density Lipoprotein-cholesterol Ratio at Week 12

Time frame:: Baseline and Week 12
Reported as:: Least squares mean · percent change

Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-cholesterol Ratio at Week 12
percent change	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM
Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-cholesterol Ratio at Week 12	1.18 ± 1.39	7.02 ± 1.67	-10.03 ± 1.39	-12.34 ± 1.68	-38.45 ± 1.02	-37.65 ± 1.21

Statistical analysis

Placebo Q2W vs Evolocumab Q2W · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -39.63 · 95% CI -42.97 to -36.30Placebo is the reference
Placebo QM vs Evolocumab QM · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -44.67 · 95% CI -48.66 to -40.68Placebo is the reference
Ezetimibe (Q2W) vs Evolocumab Q2W · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -28.42 · 95% CI -31.73 to -25.10Ezetimibe is the reference
Ezetimibe (QM) vs Evolocumab QM · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -25.31 · 95% CI -29.31 to -21.31Ezetimibe is the reference

SecondaryPercent 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
Reported as:: Least squares mean · percent change

Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12
percent change	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12	1.01 ± 1.69	3.85 ± 1.77	-13.39 ± 1.69	-14.49 ± 1.79	-48.12 ± 1.25	-51.10 ± 1.29

Statistical analysis

Placebo Q2W vs Evolocumab Q2W · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -49.12 · 95% CI -53.12 to -45.12Placebo is the reference
Placebo QM vs Evolocumab QM · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -54.95 · 95% CI -59.12 to -50.78Placebo is the reference
Ezetimibe (Q2W) vs Evolocumab Q2W · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -34.73 · 95% CI -38.73 to -30.73Ezetimibe is the reference
Ezetimibe (QM) vs Evolocumab QM · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -36.62 · 95% CI -40.81 to -32.42Ezetimibe is the reference

SecondaryPercent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12

Time frame:: Baseline and Week 12
Reported as:: Least squares mean · percent change

Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12
percent change	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12	1.12 ± 1.77	4.51 ± 1.90	-12.69 ± 1.77	-14.29 ± 1.92	-48.45 ± 1.31	-48.26 ± 1.39

Statistical analysis

Placebo Q2W vs Evolocumab Q2W · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -49.57 · 95% CI -53.78 to -45.36Placebo is the reference
Placebo QM vs Evolocumab QM · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -52.77 · 95% CI -57.28 to -48.26Placebo is the reference
Ezetimibe (Q2W) vs Evolocumab Q2W · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -35.76 · 95% CI -39.95 to -31.57Ezetimibe is the reference
Ezetimibe (QM) vs Evolocumab QM · Repeated measures linear effects model · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Ls mean treatment difference: -33.97 · 95% CI -38.48 to -29.45Ezetimibe is the reference

SecondaryPercent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12

Time frame:: Baseline and Weeks 10 and 12
Reported as:: Median · percent change

Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12
percent change	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM
Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12	0.12 ± 2.72	0.00 ± 2.96	0.00 ± 2.72	-2.08 ± 3.01	-18.37 ± 2.02	-19.24 ± 2.17

Statistical analysis

Placebo Q2W vs Evolocumab Q2W · Quade test · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: -18.48 · 95% CI -25.28 to -11.68Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Placebo QM vs Evolocumab QM · Quade test · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: -19.24 · 95% CI -23.20 to -15.28Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Ezetimibe (Q2W) vs Evolocumab Q2W · Quade test · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: -18.37 · 95% CI -24.39 to -12.35Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Ezetimibe (QM) vs Evolocumab QM · Quade test · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: -17.15 · 95% CI -23.23 to -11.08Median difference and 95% CI were obtained from McKean-Schrader algorithm.

SecondaryPercent Change From Baseline in Lipoprotein (a) at Week 12

Time frame:: Baseline and Week 12
Reported as:: Median · percent change

Percent Change From Baseline in Lipoprotein (a) at Week 12
percent change	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM
Percent Change From Baseline in Lipoprotein (a) at Week 12	0.00 ± 2.75	0.00 ± 3.26	0.00 ± 2.75	-2.05 ± 3.28	-20.41 ± 2.04	-17.82 ± 2.39

Statistical analysis

Placebo Q2W vs Evolocumab Q2W · Quade test · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: -20.41 · 95% CI -27.76 to -13.06Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Placebo QM vs Evolocumab QM · Quade test · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: -17.82 · 95% CI -24.51 to -11.12Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Ezetimibe (Q2W) vs Evolocumab Q2W · Quade test · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: -20.41 · 95% CI -28.13 to -12.69Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Ezetimibe (QM) vs Evolocumab QM · Quade test · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: -15.77 · 95% CI -24.39 to -7.14Median difference and 95% CI were obtained from McKean-Schrader algorithm.

SecondaryPercent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12

Time frame:: Baseline and Weeks 10 and 12
Reported as:: Median · percent change

Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12
percent change	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM
Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12	-3.89 ± 3.64	4.89 ± 4.02	-1.46 ± 3.60	-3.97 ± 4.04	-9.16 ± 2.65	-15.71 ± 2.92

Statistical analysis

Placebo Q2W vs Evolocumab Q2W · Quade test · p = 0.72 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: -5.27 · 95% CI -13.27 to 2.73Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Placebo QM vs Evolocumab QM · Quade test · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: -20.59 · 95% CI -30.98 to -10.20Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Ezetimibe (Q2W) vs Evolocumab Q2W · Quade test · p = 0.027 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: -7.71 · 95% CI -16.86 to 1.45Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Ezetimibe (QM) vs Evolocumab QM · Quade test · p = 0.044 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: -11.73 · 95% CI -21.19 to -2.27Median difference and 95% CI were obtained from McKean-Schrader algorithm.

SecondaryPercent Change From Baseline in Triglycerides at Week 12

Time frame:: Baseline and Week 12
Reported as:: Median · percent change

Percent Change From Baseline in Triglycerides at Week 12
percent change	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM
Percent Change From Baseline in Triglycerides at Week 12	-1.91 ± 3.13	2.01 ± 3.86	0.00 ± 3.15	-2.41 ± 3.89	-8.14 ± 2.31	-15.64 ± 2.78

Statistical analysis

Placebo Q2W vs Evolocumab Q2W · Quade test · p = 0.72 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: -6.23 · 95% CI -16.41 to 3.95Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Placebo QM vs Evolocumab QM · Quade test · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: -17.65 · 95% CI -26.67 to -8.63Median difference and 95% CI were obtained from McKean-Schrader algorithm
Ezetimibe (Q2W) vs Evolocumab Q2W · Quade test · p = 0.027 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: -8.14 · 95% CI -17.54 to 1.26Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Ezetimibe (QM) vs Evolocumab QM · Quade test · p = 0.044 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: -13.23 · 95% CI -21.69 to -4.77Median difference and 95% CI were obtained from McKean-Schrader algorithm.

SecondaryPercent Change From Baseline in Very Low Density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12

Time frame:: Baseline and Weeks 10 and 12
Reported as:: Median · percent change

Percent Change From Baseline in Very Low Density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12
percent change	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM
Percent Change From Baseline in Very Low Density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12	-3.81 ± 3.09	4.22 ± 3.70	-2.69 ± 3.12	-3.33 ± 3.69	-8.40 ± 2.28	-16.17 ± 2.65

Statistical analysis

Placebo Q2W vs Evolocumab Q2W · Quade test · p = 0.072 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: -4.59 · 95% CI -11.30 to 2.12Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Placebo QM vs Evolocumab QM · Quade test · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: -20.39 · 95% CI -30.11 to -10.68Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Ezetimibe (Q2W) vs Evolocumab Q2W · Quade test · p = 0.082 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: -5.71 · 95% CI -14.13 to 2.71Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Ezetimibe (QM) vs Evolocumab QM · Quade test · p = 0.044 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: -12.84 · 95% CI -22.14 to -3.54Median difference and 95% CI were obtained from McKean-Schrader algorithm.

SecondaryPercent Change From Baseline in VLDL-C at Week 12

Time frame:: Baseline and Week 12
Reported as:: Median · percent change

Percent Change From Baseline in VLDL-C at Week 12
percent change	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM
Percent Change From Baseline in VLDL-C at Week 12	-1.58 ± 3.67	0.00 ± 3.93	-0.94 ± 3.65	-3.61 ± 3.87	-9.52 ± 2.64	-16.33 ± 2.80

Statistical analysis

Placebo Q2W vs Evolocumab Q2W · Quade test · p = 0.72 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: -7.94 · 95% CI -18.81 to 2.92Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Placebo QM vs Evolocumab QM · Quade test · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: -16.33 · 95% CI -25.64 to -7.02Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Ezetimibe (Q2W) vs Evolocumab Q2W · Quade test · p = 0.082 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: -8.58 · 95% CI -18.10 to 0.94Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Ezetimibe (QM) vs Evolocumab QM · Quade test · p = 0.044 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: -12.72 · 95% CI -20.89 to -4.54Median difference and 95% CI were obtained from McKean-Schrader algorithm.

SecondaryPercent 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
Reported as:: Median · percent change

Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at the Mean of Weeks 10 and 12
percent change	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM
Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at the Mean of Weeks 10 and 12	-1.64 ± 1.26	-4.67 ± 1.32	-0.92 ± 1.27	0.00 ± 1.33	3.89 ± 0.93	3.81 ± 0.95

Statistical analysis

Placebo Q2W vs Evolocumab Q2W · Quade test · p = 0.007 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: 5.53 · 95% CI 2.23 to 8.84Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Placebo QM vs Evolocumab QM · Quade test · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: 8.48 · 95% CI 5.53 to 11.43Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Ezetimibe (Q2W) vs Evolocumab Q2W · Quade test · p = 0.013 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: 4.81 · 95% CI 0.85 to 8.78Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Ezetimibe (QM) vs Evolocumab QM · Quade test · p = 0.044 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: 3.81 · 95% CI -0.77 to 8.39Median difference and 95% CI were obtained from McKean-Schrader algorithm.

SecondaryPercent Change From Baseline in HDL-C at Week 12

Time frame:: Baseline and Week 12
Reported as:: Median · percent change

Percent Change From Baseline in HDL-C at Week 12
percent change	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM
Percent Change From Baseline in HDL-C at Week 12	-1.15 ± 1.43	-5.27 ± 1.40	-2.79 ± 1.42	-1.47 ± 1.41	4.76 ± 1.05	4.06 ± 1.01

Statistical analysis

Placebo Q2W vs Evolocumab Q2W · Quade test · p = 0.007 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: 5.91 · 95% CI 1.67 to 10.16Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Placebo QM vs Evolocumab QM · Quade test · p = <0.001 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: 9.33 · 95% CI 5.32 to 13.34Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Ezetimibe (Q2W) vs Evolocumab Q2W · Quade test · p = 0.013 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: 7.56 · 95% CI 3.11 to 12.00Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Ezetimibe (QM) vs Evolocumab QM · Quade test · p = 0.044 (Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.) · Median treatment difference: 5.53 · 95% CI 2.22 to 8.84Median difference and 95% CI were obtained from McKean-Schrader algorithm.

Adverse events

Collected over From the first dose of blinded investigational product until the end of the study (up to 14 weeks).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Placebo Q2W	—	0/76 (0%)	9/76 (11.8%)
Placebo QM	—	1/78 (1.3%)	4/78 (5.1%)
Ezetimibe (Q2W)	—	0/77 (0%)	10/77 (13%)
Ezetimibe (QM)	—	1/77 (1.3%)	4/77 (5.2%)
Evolocumab Q2W	—	3/153 (2%)	12/153 (7.8%)
Evolocumab QM	—	1/153 (0.7%)	12/153 (7.8%)

Most frequent serious events

Most frequent serious events
Event	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM
Breast cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)	0/76	0/78	0/77	1/77	0/153	0/153
Bladder cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)	0/76	1/78	0/77	0/77	0/153	0/153
Pancreatitis acuteGastrointestinal disorders	0/76	0/78	0/77	0/77	0/153	1/153
Upper limb fractureInjury, poisoning and procedural complications	0/76	0/78	0/77	0/77	1/153	0/153
Hepatic enzyme increasedInvestigations	0/76	0/78	0/77	0/77	1/153	0/153
Renal cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)	0/76	0/78	0/77	0/77	1/153	0/153
Pleural effusionRespiratory, thoracic and mediastinal disorders	0/76	0/78	0/77	0/77	1/153	0/153

Most frequent other events

Most frequent other events
Event	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM
DiarrhoeaGastrointestinal disorders	5/76	1/78	2/77	1/77	4/153	5/153
NasopharyngitisInfections and infestations	1/76	2/78	4/77	2/77	3/153	3/153
HeadacheNervous system disorders	3/76	1/78	4/77	1/77	5/153	5/153

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM	Total
Mean	54.4 ± 10.3	52.6 ± 10.7	53.9 ± 11.3	53.0 ± 12.7	52.5 ± 13.7	52.9 ± 12.1	53.1 ± 12.1

Sex: Female, Male
Sex: Female, Male(Participants)	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM	Total
Female	49	47	53	52	104	101	406
Male	28	31	24	25	49	52	209

Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM	Total
American Indian or Alaska Native	0	0	0	1	0	2	3
Asian	9	8	7	10	12	12	58
Black or African American	4	6	6	6	9	9	40
Native Hawaiian or Other Pacific Islander	0	1	0	0	0	0	1
White	64	63	63	60	132	129	511
Other	0	0	0	0	0	0	0
Mixed Race	0	0	1	0	0	1	2

Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM	Total
Hispanic or Latino	6	8	9	11	14	21	69
Not Hispanic or Latino	71	70	68	66	139	132	546

Stratification Factor: Low-density Lipoprotein Cholesterol (LDL-C)
Stratification Factor: Low-density Lipoprotein Cholesterol (LDL-C)(participants)	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM	Total
< 130 mg/dL	23	24	22	22	45	45	181
≥ 130 mg/dL	54	54	55	55	108	108	434

LDL-C Concentration
LDL-C Concentration(mg/dL)	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM	Total
Mean	139.5 ± 21.3	144.3 ± 23.9	143.3 ± 23.8	143.5 ± 23.1	141.7 ± 22.3	144.4 ± 23.3	142.9 ± 22.9

Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) Concentration
Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) Concentration(mg/dL)	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM	Total
Mean	167.4 ± 25.8	172.8 ± 31.0	168.8 ± 28.9	169.4 ± 27.3	166.5 ± 25.6	170.4 ± 26.6	169.0 ± 27.2

Apolipoprotein B Concentration
Apolipoprotein B Concentration(mg/dL)	Placebo Q2W	Placebo QM	Ezetimibe (Q2W)	Ezetimibe (QM)	Evolocumab Q2W	Evolocumab QM	Total
Mean	103.7 ± 16.8	107.3 ± 19.9	107.2 ± 19.7	106.2 ± 17.8	104.5 ± 17.2	108.3 ± 17.9	106.2 ± 18.1

6 further baseline measures are reported on the registry.

Study locations

83 sites

Research Site
Birmingham, Alabama 35216, United States
Research Site
Chandler, Arizona 85224, United States
Research Site
Little Rock, Arkansas 72205, United States
Research Site
Carmichael, California 95608, United States
Research Site
Encinitas, California 92024, United States
Research Site
San Diego, California 92111, United States
Research Site
Tustin, California 92780, United States
Research Site
Jacksonville, Florida 32204, United States
Research Site
Jacksonville, Florida 32216, United States
Research Site
Miami, Florida 33144, United States
Research Site
Ponte Vedra, Florida 32081, United States
Research Site
Sanford, Florida 32771, United States
Research Site
Boise, Idaho 83704, United States
Research Site
Chicago, Illinois 60654, United States
Research Site
Indianapolis, Indiana 46260, United States
Research Site
Overland Park, Kansas 66202, United States
Research Site
Louisville, Kentucky 40213, United States
Research Site
Bethesda, Maryland 20817, United States
Research Site
Brockton, Massachusetts 02301, United States
Research Site
Edina, Minnesota 55435, United States
Research Site
Olive Branch, Mississippi 38654, United States
Research Site
Las Vegas, Nevada 89148, United States
Research Site
Endwell, New York 13760, United States
Research Site
New Windsor, New York 12553, United States
Research Site
Raleigh, North Carolina 27609, United States
Research Site
Raleigh, North Carolina 27612, United States
Research Site
Fargo, North Dakota 58103, United States
Research Site
Akron, Ohio 44311, United States
Research Site
Cincinnati, Ohio 45212, United States
Research Site
Cincinnati, Ohio 45236, United States
Research Site
Cincinnati, Ohio 45246, United States
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Cleveland, Ohio 44122, United States
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Norman, Oklahoma 73069, United States
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Oklahoma City, Oklahoma 73103, United States
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Duncansville, Pennsylvania 16635, United States
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Anderson, South Carolina 29621, United States
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Mount Pleasant, South Carolina 29464, United States
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Rapid City, South Dakota 57702, United States
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Jackson, Tennessee 38305, United States
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Boerne, Texas 78006, United States
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Dallas, Texas 75230, United States
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San Antonio, Texas 78205, United States
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Salt Lake City, Utah 84124, United States
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Norfolk, Virginia 23502, United States
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Richmond, Virginia 23294, United States
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Renton, Washington 98057, United States
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Seattle, Washington 98104, United States
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Darlinghurst, New South Wales 2010, Australia
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Maroubra, New South Wales 2035, Australia
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Carina Heights, Queensland 4152, Australia
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Sherwood, Queensland 4075, Australia
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Anthée, 5520, Belgium
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Bruxelles, 1080, Belgium
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Gozee, 6534, Belgium
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Gribomont, 6887, Belgium
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Halen, 3545, Belgium
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Ham, 3945, Belgium
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Linkebeek, 1630, Belgium
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Retie, 2470, Belgium
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Tessenderlo, 3980, Belgium
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Bay Roberts, Newfoundland and Labrador A0A 1G0, Canada
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Mount Pearl, Newfoundland and Labrador A1N 1W7, Canada
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Toronto, Ontario M9W 4L6, Canada
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Granby, Quebec J2G 8Z9, Canada
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Aalborg, 9000, Denmark
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Ballerup, 2750, Denmark
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Vejle, 7100, Denmark
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Gières, 38610, France
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Grenoble Cedex 9, 38043, France
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Seoul, 120-752, Korea, Republic of
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Seoul, 135-710, Korea, Republic of
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Seoul, 138-736, Korea, Republic of
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Alberton, Gauteng 1449, South Africa
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Johannesburg, Gauteng 2196, South Africa
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Parow, Western Cape 7505, South Africa
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Somerset West, Western Cape 7130, South Africa
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Worcester, Western Cape 6850, South Africa
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Bloemfontein, 9301, South Africa
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Kaohsiung, 807, Taiwan
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Kaohsiung, 83301, Taiwan
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Taipei, 100, Taiwan
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Istanbul, 34093, Turkey
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Istanbul, 34662, Turkey

References and documents

Publications

Koren MJ, Lundqvist P, Bolognese M, Neutel JM, Monsalvo ML, Yang J, Kim JB, Scott R, Wasserman SM, Bays H; MENDEL-2 Investigators. Anti-PCSK9 monotherapy for hypercholesterolemia: the MENDEL-2 randomized, controlled phase III clinical trial of evolocumab. J Am Coll Cardiol. 2014 Jun 17;63(23):2531-2540. doi: 10.1016/j.jacc.2014.03.018. Epub 2014 Mar 29. PubMed 24691094 ↗
Daviglus ML, Ferdinand KC, Lopez JAG, Wu Y, Monsalvo ML, Rodriguez CJ. Effects of Evolocumab on Low-Density Lipoprotein Cholesterol, Non-High Density Lipoprotein Cholesterol, Apolipoprotein B, and Lipoprotein(a) by Race and Ethnicity: A Meta-Analysis of Individual Participant Data From Double-Blind and Open-Label Extension Studies. J Am Heart Assoc. 2021 Jan 5;10(1):e016839. doi: 10.1161/JAHA.120.016839. Epub 2020 Dec 16. PubMed 33325247 ↗
Koren MJ, Jones PH, Robinson JG, Sullivan D, Cho L, Hucko T, Lopez JAG, Fleishman AN, Somaratne R, Stroes E. A Comparison of Ezetimibe and Evolocumab for Atherogenic Lipid Reduction in Four Patient Populations: A Pooled Efficacy and Safety Analysis of Three Phase 3 Studies. Cardiol Ther. 2020 Dec;9(2):447-465. doi: 10.1007/s40119-020-00181-8. Epub 2020 Jun 20. PubMed 32564340 ↗
Kuchimanchi M, Grover A, Emery MG, Somaratne R, Wasserman SM, Gibbs JP, Doshi S. Population pharmacokinetics and exposure-response modeling and simulation for evolocumab in healthy volunteers and patients with hypercholesterolemia. J Pharmacokinet Pharmacodyn. 2018 Jun;45(3):505-522. doi: 10.1007/s10928-018-9592-y. Epub 2018 May 7. PubMed 29736889 ↗
Kasichayanula S, Grover A, Emery MG, Gibbs MA, Somaratne R, Wasserman SM, Gibbs JP. Clinical Pharmacokinetics and Pharmacodynamics of Evolocumab, a PCSK9 Inhibitor. Clin Pharmacokinet. 2018 Jul;57(7):769-779. doi: 10.1007/s40262-017-0620-7. PubMed 29353350 ↗
Shapiro MD, Minnier J, Tavori H, Kassahun H, Flower A, Somaratne R, Fazio S. Relationship Between Low-Density Lipoprotein Cholesterol and Lipoprotein(a) Lowering in Response to PCSK9 Inhibition With Evolocumab. J Am Heart Assoc. 2019 Feb 19;8(4):e010932. doi: 10.1161/JAHA.118.010932. PubMed 30755061 ↗
Stroes E, Robinson JG, Raal FJ, Dufour R, Sullivan D, Kassahun H, Ma Y, Wasserman SM, Koren MJ. Consistent LDL-C response with evolocumab among patient subgroups in PROFICIO: A pooled analysis of 3146 patients from phase 3 studies. Clin Cardiol. 2018 Oct;41(10):1328-1335. doi: 10.1002/clc.23049. Epub 2018 Oct 21. PubMed 30120772 ↗
Toth PP, Descamps O, Genest J, Sattar N, Preiss D, Dent R, Djedjos C, Wu Y, Geller M, Uhart M, Somaratne R, Wasserman SM; PROFICIO Investigators. Pooled Safety Analysis of Evolocumab in Over 6000 Patients From Double-Blind and Open-Label Extension Studies. Circulation. 2017 May 9;135(19):1819-1831. doi: 10.1161/CIRCULATIONAHA.116.025233. Epub 2017 Mar 1. PubMed 28249876 ↗
Toth PP, Jones SR, Monsalvo ML, Elliott-Davey M, Lopez JAG, Banach M. Effect of Evolocumab on Non-High-Density Lipoprotein Cholesterol, Apolipoprotein B, and Lipoprotein(a): A Pooled Analysis of Phase 2 and Phase 3 Studies. J Am Heart Assoc. 2020 Mar 3;9(5):e014129. doi: 10.1161/JAHA.119.014129. Epub 2020 Mar 2. PubMed 32114889 ↗
Wasserman SM, Sabatine MS, Koren MJ, Giugliano RP, Legg JC, Emery MG, Doshi S, Liu T, Somaratne R, Gibbs JP. Comparison of LDL-C Reduction Using Different Evolocumab Doses and Intervals: Biological Insights and Treatment Implications. J Cardiovasc Pharmacol Ther. 2018 Sep;23(5):423-432. doi: 10.1177/1074248418774043. Epub 2018 May 16. PubMed 29768954 ↗
May HT, Muhlestein JB, Ma Y, Lopez JAG, Coll B, Nelson J. Effects of Evolocumab on the ApoA1 Remnant Ratio: A Pooled Analysis of Phase 3 Studies. Cardiol Ther. 2019 Jun;8(1):91-102. doi: 10.1007/s40119-019-0133-6. Epub 2019 Mar 9. PubMed 30852766 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Nov 8, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01763827
Lead sponsor: Amgen
Responsible party: Sponsor
First posted: Jan 9, 2013
Start date: Jan 21, 2013
Primary completion: Oct 10, 2013
Completion: Oct 29, 2013
Results posted: Dec 30, 2015
Last update: Nov 8, 2022

Study contacts

study director · Amgen

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy for Easing Lipid Levels-2

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