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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 (MENDEL-2)

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ClinicalTrials.gov Identifier: NCT01763827
Recruitment Status : Completed
First Posted : January 9, 2013
Results First Posted : December 30, 2015
Last Update Posted : November 28, 2018
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Hyperlipidemia
Interventions Biological: Evolocumab
Drug: Ezetimibe
Biological: Placebo to Evolocumab
Other: Placebo to Ezetimibe
Enrollment 615
Recruitment Details 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.
Pre-assignment Details Participants received subcutaneous placebo corresponding to the once monthly dose volume during a 6 week screening period. Participants who completed the screening period and met final eligibility criteria were randomized 1:1:1:1:2:2 into 6 treatment groups. Randomization was stratified by LDL-C concentration (< 130 mg/dL or ≥ 30 mg/dL).
Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
Period Title: Overall Study
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
Reason Not Completed
Withdrawal by Subject             1             0             0             0             2             0
Decision by sponsor             2             0             3             0             2             1
Lost to Follow-up             0             1             1             1             2             1
Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM Total
Hide Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks. Total of all reporting groups
Overall Number of Baseline Participants 77 78 77 77 153 153 615
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 77 participants 78 participants 77 participants 77 participants 153 participants 153 participants 615 participants
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  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 78 participants 77 participants 77 participants 153 participants 153 participants 615 participants
Female
49
  63.6%
47
  60.3%
53
  68.8%
52
  67.5%
104
  68.0%
101
  66.0%
406
  66.0%
Male
28
  36.4%
31
  39.7%
24
  31.2%
25
  32.5%
49
  32.0%
52
  34.0%
209
  34.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 77 participants 78 participants 77 participants 77 participants 153 participants 153 participants 615 participants
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  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 77 participants 78 participants 77 participants 77 participants 153 participants 153 participants 615 participants
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)  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 77 participants 78 participants 77 participants 77 participants 153 participants 153 participants 615 participants
< 130 mg/dL 23 24 22 22 45 45 181
≥ 130 mg/dL 54 54 55 55 108 108 434
LDL-C Concentration   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 77 participants 78 participants 77 participants 77 participants 153 participants 153 participants 615 participants
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)
[1]
Measure Description: Data are provided for the full analysis set (all randomized participants who received at least 1 dose of investigational product (subcutaneously or orally).
Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) Concentration   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 77 participants 78 participants 77 participants 77 participants 153 participants 153 participants 615 participants
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)
[1]
Measure Description: Data are provided for the full analysis set
Apolipoprotein B Concentration   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 77 participants 78 participants 77 participants 77 participants 153 participants 153 participants 615 participants
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)
[1]
Measure Description: Data are provided for the full analysis set
Total Cholesterol/High-density Lipoprotein Cholesterol Ratio   [1] 
Mean (Standard Deviation)
Unit of measure:  Ratio
Number Analyzed 77 participants 78 participants 77 participants 77 participants 153 participants 153 participants 615 participants
4.148  (1.311) 4.444  (1.465) 4.055  (1.082) 4.335  (1.118) 4.170  (1.170) 4.175  (1.071) 4.210  (1.191)
[1]
Measure Description: Data are provided for the full analysis set
Apolipoprotein B/Apolipoprotein A-1 Ratio   [1] 
Mean (Standard Deviation)
Unit of measure:  Ratio
Number Analyzed 77 participants 78 participants 77 participants 77 participants 153 participants 153 participants 615 participants
0.671  (0.193) 0.713  (0.194) 0.691  (0.187) 0.712  (0.173) 0.687  (0.169) 0.707  (0.170) 0.697  (0.178)
[1]
Measure Description: Data are provided for the full analysis set
Lipoprotein(a)   [1] 
Median (Inter-Quartile Range)
Unit of measure:  nmol/L
Number Analyzed 77 participants 78 participants 77 participants 77 participants 153 participants 153 participants 615 participants
21.0
(9.0 to 49.0)
21.5
(7.0 to 62.0)
28.0
(11.0 to 120.0)
28.0
(12.0 to 64.0)
20.0
(7.0 to 58.0)
28.0
(9.0 to 104.0)
25.0
(9.0 to 71.0)
[1]
Measure Description: Data are provided for the full analysis set
Triglycerides   [1] 
Median (Inter-Quartile Range)
Unit of measure:  mg/dL
Number Analyzed 77 participants 78 participants 77 participants 77 participants 153 participants 153 participants 615 participants
113.5
(83.3 to 178.0)
118.0
(85.5 to 178.5)
112.5
(83.5 to 158.0)
116.5
(90.0 to 159.0)
112.0
(81.5 to 147.5)
119.0
(82.5 to 168.5)
115.3
(83.5 to 163.0)
[1]
Measure Description: Data are provided for the full analysis set
Very Low-density Lipoprotein Cholesterol (VLDL-C) Concentration   [1] 
Median (Inter-Quartile Range)
Unit of measure:  mg/dL
Number Analyzed 77 participants 78 participants 77 participants 77 participants 153 participants 153 participants 615 participants
22.5
(16.8 to 34.3)
23.8
(17.0 to 35.5)
22.5
(16.5 to 32.0)
23.5
(18.0 to 31.5)
22.5
(16.5 to 29.5)
23.5
(16.5 to 33.5)
23.0
(16.5 to 32.5)
[1]
Measure Description: Data are provided for the full analysis set
High-density Lipoprotein Cholesterol (HDL-C) Concentration   [1] 
Median (Inter-Quartile Range)
Unit of measure:  mg/dL
Number Analyzed 77 participants 78 participants 77 participants 77 participants 153 participants 153 participants 615 participants
57.0
(43.8 to 77.3)
54.0
(44.5 to 65.5)
58.5
(47.0 to 69.5)
53.5
(42.0 to 67.5)
53.0
(44.5 to 67.0)
56.5
(46.5 to 65.5)
55.3
(44.5 to 67.5)
[1]
Measure Description: Data are provided for the full analysis set
1.Primary Outcome
Title Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12
Hide Description [Not Specified]
Time Frame Baseline and Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
Overall Number of Participants Analyzed 76 78 77 77 153 153
Least Squares Mean (Standard Error)
Unit of Measure: percent change
0.10  (1.67) -1.34  (1.54) -17.75  (1.67) -18.57  (1.56) -57.04  (1.23) -56.12  (1.12)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
Comments 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 placebo, and the alternative hypothesis was that a mean difference did exist.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model included treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -57.14
Confidence Interval (2-Sided) 95%
-61.14 to -53.14
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.03
Estimation Comments Placebo is the reference
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
Comments 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 placebo, and the alternative hypothesis was that a mean difference did exist.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -54.78
Confidence Interval (2-Sided) 95%
-58.46 to -51.10
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.87
Estimation Comments Placebo is the reference
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -39.29
Confidence Interval (2-Sided) 95%
-43.28 to -35.31
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.03
Estimation Comments Ezetimibe is the reference
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -37.55
Confidence Interval (2-Sided) 95%
-41.24 to -33.86
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.88
Estimation Comments Ezetimibe is the reference
2.Primary Outcome
Title Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
Hide Description [Not Specified]
Time Frame Baseline and Weeks 10 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
Overall Number of Participants Analyzed 76 78 77 77 153 153
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-0.43  (1.45) -1.41  (1.37) -17.52  (1.46) -19.12  (1.39) -56.93  (1.07) -58.81  (1.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
Comments The null hypothesis was that there was no mean difference in the percent change from Baseline at the mean of Weeks 10 and 12 in LDL-C between evolocumab and placebo, and the alternative hypothesis was that a mean difference did exist.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -56.50
Confidence Interval (2-Sided) 95%
-59.95 to -53.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.76
Estimation Comments Placebo is the reference
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
Comments The null hypothesis was that there was no mean difference in the percent change from Baseline at the mean of Weeks 10 and 12 in LDL-C between evolocumab and placebo, and the alternative hypothesis was that a mean difference did exist.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -57.40
Confidence Interval (2-Sided) 95%
-60.66 to -54.14
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.66
Estimation Comments Placebo is the reference
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
Comments The null hypothesis was that there was no mean difference in the percent change from Baseline at the mean of Weeks 10 and 12 in LDL-C between evolocumab and ezetimibe, and the alternative hypothesis was that a mean difference did exist.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -39.41
Confidence Interval (2-Sided) 95%
-42.87 to -35.94
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.76
Estimation Comments Ezetimibe is the reference
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
Comments The null hypothesis was that there was no mean difference in the percent change from Baseline at the mean of Weeks 10 and 12 in LDL-C between evolocumab and ezetimibe, and the alternative hypothesis was that a mean difference did exist.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -36.69
Confidence Interval (2-Sided) 95%
-42.97 to -36.42
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.66
Estimation Comments Ezetimibe is the reference
3.Secondary Outcome
Title Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
Hide Description [Not Specified]
Time Frame Baseline and Weeks 10 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
Overall Number of Participants Analyzed 76 78 77 77 153 153
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
1.2  (2.3) 0.0  (2.1) -23.1  (2.3) -25.9  (2.1) -78.4  (1.7) -81.9  (1.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -79.6
Confidence Interval (2-Sided) 95%
-85.0 to -74.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.7
Estimation Comments Placebo is the reference
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -81.9
Confidence Interval (2-Sided) 95%
-87.0 to -76.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.6
Estimation Comments Placebo is the reference
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -55.3
Confidence Interval (2-Sided) 95%
-60.7 to -49.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.7
Estimation Comments Ezetimibe is the reference
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -56.1
Confidence Interval (2-Sided) 95%
-61.1 to -51.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.6
Estimation Comments Ezetimibe is the reference
4.Secondary Outcome
Title Change From Baseline in LDL-C at Week 12
Hide Description [Not Specified]
Time Frame Baseline and Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
Overall Number of Participants Analyzed 76 78 77 77 153 153
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
1.9  (2.5) -0.1  (2.4) -23.4  (2.5) -25.0  (2.4) -78.4  (1.9) -77.9  (1.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -80.4
Confidence Interval (2-Sided) 95%
-86.4 to -74.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.1
Estimation Comments Placebo is the reference
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -77.8
Confidence Interval (2-Sided) 95%
-83.4 to -72.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.8
Estimation Comments Placebo is the reference
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -55.0
Confidence Interval (2-Sided) 95%
-61.1 to -49.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.1
Estimation Comments Ezetimibe was the reference
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, stratification factor, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -52.9
Confidence Interval (2-Sided) 95%
-58.5 to -47.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.9
Estimation Comments Ezetimibe was the reference
5.Secondary Outcome
Title Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL
Hide Description [Not Specified]
Time Frame Weeks 10 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
Overall Number of Participants Analyzed 76 78 77 77 153 153
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
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)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Cochran-Mantel-Haenszel
Comments Based on CMH test stratified by Baseline LDL-C level. For testing, non-achievement was imputed for participants with a missing value.
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 73.6
Confidence Interval (2-Sided) 95%
64.4 to 80.2
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Cochran-Mantel-Haenszel
Comments Based on CMH test stratified by Baseline LDL-C level. For testing, non-achievement was imputed for participants with a missing value.
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 71.3
Confidence Interval (2-Sided) 95%
62.2 to 78.0
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Cochran-Mantel-Haenszel
Comments Based on CMH test stratified by Baseline LDL-C level. For testing, non-achievement was imputed for participants with a missing value.
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 72.2
Confidence Interval (2-Sided) 95%
62.4 to 78.9
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Cochran-Mantel-Haenszel
Comments Based on CMH test stratified by Baseline LDL-C level. For testing, non-achievement was imputed for participants with a missing value.
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 68.6
Confidence Interval (2-Sided) 95%
58.3 to 75.5
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12
Hide Description [Not Specified]
Time Frame Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
Overall Number of Participants Analyzed 76 78 77 77 153 153
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
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)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Cochran-Mantel-Haenszel
Comments Based on CMH test stratified by Baseline LDL-C level. For testing, non-achievement was imputed for participants with a missing value.
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 71.5
Confidence Interval (2-Sided) 95%
61.2 to 78.4
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Cochran-Mantel-Haenszel
Comments Based on CMH test stratified by Baseline LDL-C level. For testing, non-achievement was imputed for participants with a missing value.
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 65.4
Confidence Interval (2-Sided) 95%
55.6 to 72.9
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Cochran-Mantel-Haenszel
Comments Based on CMH test stratified by Baseline LDL-C level. For testing, non-achievement was imputed for participants with a missing value.
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 71.5
Confidence Interval (2-Sided) 95%
61.3 to 78.4
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Cochran-Mantel-Haenszel
Comments Based on CMH test stratified by Baseline LDL-C level. For testing, non-achievement was imputed for participants with a missing value.
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 64.0
Confidence Interval (2-Sided) 95%
53.5 to 71.6
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 10 and 12
Hide Description [Not Specified]
Time Frame Baseline and Weeks 10 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
Overall Number of Participants Analyzed 76 78 77 77 153 153
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-1.41  (1.34) 1.32  (1.24) -14.64  (1.35) -16.48  (1.25) -50.22  (0.99) -51.96  (0.90)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -48.81
Confidence Interval (2-Sided) 95%
-52.01 to -45.61
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.63
Estimation Comments Placebo is the reference
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -53.28
Confidence Interval (2-Sided) 95%
-56.23 to -50.33
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.50
Estimation Comments Placebo is the reference
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -35.58
Confidence Interval (2-Sided) 95%
-38.79 to -32.38
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.63
Estimation Comments Ezetimibe is the reference
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -35.49
Confidence Interval (2-Sided) 95%
-38.44 to -32.53
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.50
Estimation Comments Ezetimibe is the reference
8.Secondary Outcome
Title Percent Change From Baseline in Non-HDL-C at Week 12
Hide Description [Not Specified]
Time Frame Baseline and Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
Overall Number of Participants Analyzed 76 78 77 77 153 153
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-0.31  (1.48) 1.51  (1.38) -14.89  (1.47) -16.48  (1.39) -50.12  (1.08) -49.68  (1.01)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -49.81
Confidence Interval (2-Sided) 95%
-53.34 to -46.27
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.79
Estimation Comments Placebo is the reference
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -51.19
Confidence Interval (2-Sided) 95%
-54.49 to -47.90
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.67
Estimation Comments Placebo is the reference
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -35.23
Confidence Interval (2-Sided) 95%
-38.74 to -31.71
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.78
Estimation Comments Ezetimibe is the reference
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -33.21
Confidence Interval (2-Sided) 95%
-36.51 to -29.90
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.68
Estimation Comments Ezetimibe is the reference
9.Secondary Outcome
Title Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12
Hide Description [Not Specified]
Time Frame Baseline and Weeks 10 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
Overall Number of Participants Analyzed 76 78 77 77 153 153
Least Squares Mean (Standard Error)
Unit of Measure: percent change
0.05  (1.51) 1.54  (1.41) -13.47  (1.52) -14.75  (1.43) -47.04  (1.12) -49.39  (1.03)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -47.09
Confidence Interval (2-Sided) 95%
-50.67 to -43.51
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.82
Estimation Comments Placebo is the reference
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -50.93
Confidence Interval (2-Sided) 95%
-54.27 to -47.59
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.70
Estimation Comments Placebo is the reference
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -33.57
Confidence Interval (2-Sided) 95%
-37.15 to -29.99
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.82
Estimation Comments Ezetimibe is the reference
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -34.64
Confidence Interval (2-Sided) 95%
-37.99 to -31.28
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.71
Estimation Comments Ezetimibe is the reference
10.Secondary Outcome
Title Percent Change From Baseline in Apolipoprotein B at Week 12
Hide Description [Not Specified]
Time Frame Baseline and Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
Overall Number of Participants Analyzed 76 78 77 77 153 153
Least Squares Mean (Standard Error)
Unit of Measure: percent change
0.59  (1.58) 1.84  (1.53) -13.17  (1.58) -14.02  (1.54) -47.21  (1.17) -46.59  (1.12)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -47.81
Confidence Interval (2-Sided) 95%
-51.56 to -44.05
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.91
Estimation Comments Placebo is the reference
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -48.43
Confidence Interval (2-Sided) 95%
-52.07 to -44.79
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.85
Estimation Comments Placebo is the reference
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -34.04
Confidence Interval (2-Sided) 95%
-37.78 to -30.30
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.90
Estimation Comments Ezetimibe is the reference
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -32.57
Confidence Interval (2-Sided) 95%
-36.21 to -28.92
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.85
Estimation Comments Ezetimibe is the reference
11.Secondary Outcome
Title Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-cholesterol Ratio at the Mean of Weeks 10 and 12
Hide Description [Not Specified]
Time Frame Baseline and Weeks 10 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
Overall Number of Participants Analyzed 76 78 77 77 153 153
Least Squares Mean (Standard Error)
Unit of Measure: percent change
0.44  (1.29) 6.42  (1.50) -9.14  (1.29) -11.90  (1.51) -38.49  (0.95) -39.41  (1.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -38.93
Confidence Interval (2-Sided) 95%
-42.00 to -35.86
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.56
Estimation Comments Placebo is the reference
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -45.83
Confidence Interval (2-Sided) 95%
-49.39 to -42.27
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.81
Estimation Comments Placebo is the reference
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -29.36
Confidence Interval (2-Sided) 95%
-32.43 to -26.28
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.56
Estimation Comments Ezetimibe is the reference
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -27.51
Confidence Interval (2-Sided) 95%
-31.08 to -23.94
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.81
Estimation Comments Ezetimibe is the reference
12.Secondary Outcome
Title Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-cholesterol Ratio at Week 12
Hide Description [Not Specified]
Time Frame Baseline and Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
Overall Number of Participants Analyzed 76 78 77 77 153 153
Least Squares Mean (Standard Error)
Unit of Measure: percent change
1.18  (1.39) 7.02  (1.67) -10.03  (1.39) -12.34  (1.68) -38.45  (1.02) -37.65  (1.21)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -39.63
Confidence Interval (2-Sided) 95%
-42.97 to -36.30
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.69
Estimation Comments Placebo is the reference
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -44.67
Confidence Interval (2-Sided) 95%
-48.66 to -40.68
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.03
Estimation Comments Placebo is the reference
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -28.42
Confidence Interval (2-Sided) 95%
-31.73 to -25.10
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.68
Estimation Comments Ezetimibe is the reference
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -25.31
Confidence Interval (2-Sided) 95%
-29.31 to -21.31
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.03
Estimation Comments Ezetimibe is the reference
13.Secondary Outcome
Title Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12
Hide Description [Not Specified]
Time Frame Baseline and Weeks 10 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
Overall Number of Participants Analyzed 76 78 77 77 153 153
Least Squares Mean (Standard Error)
Unit of Measure: percent change
1.01  (1.69) 3.85  (1.77) -13.39  (1.69) -14.49  (1.79) -48.12  (1.25) -51.10  (1.29)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -49.12
Confidence Interval (2-Sided) 95%
-53.12 to -45.12
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.03
Estimation Comments Placebo is the reference
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -54.95
Confidence Interval (2-Sided) 95%
-59.12 to -50.78
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.12
Estimation Comments Placebo is the reference
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -34.73
Confidence Interval (2-Sided) 95%
-38.73 to -30.73
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.03
Estimation Comments Ezetimibe is the reference
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -36.62
Confidence Interval (2-Sided) 95%
-40.81 to -32.42
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.13
Estimation Comments Ezetimibe is the reference
14.Secondary Outcome
Title Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12
Hide Description [Not Specified]
Time Frame Baseline and Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
Overall Number of Participants Analyzed 76 78 77 77 153 153
Least Squares Mean (Standard Error)
Unit of Measure: percent change
1.12  (1.77) 4.51  (1.90) -12.69  (1.77) -14.29  (1.92) -48.45  (1.31) -48.26  (1.39)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -49.57
Confidence Interval (2-Sided) 95%
-53.78 to -45.36
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.14
Estimation Comments Placebo is the reference
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -52.77
Confidence Interval (2-Sided) 95%
-57.28 to -48.26
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.29
Estimation Comments Placebo is the reference
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -35.76
Confidence Interval (2-Sided) 95%
-39.95 to -31.57
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.13
Estimation Comments Ezetimibe is the reference
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Repeated measures linear effects model
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -33.97
Confidence Interval (2-Sided) 95%
-38.48 to -29.45
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.29
Estimation Comments Ezetimibe is the reference
15.Secondary Outcome
Title Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12
Hide Description [Not Specified]
Time Frame Baseline and Weeks 10 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
Overall Number of Participants Analyzed 76 78 77 77 153 153
Median (Inter-Quartile Range)
Unit of Measure: percent change
0.12
(-11.11 to 11.50)
0.00
(-11.82 to 8.33)
0.00
(-9.60 to 10.31)
-2.08
(-18.18 to 5.56)
-18.37
(-37.50 to 0.00)
-19.24
(-38.80 to -4.79)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments Adjusted for Baseline value
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value -18.48
Confidence Interval (2-Sided) 95%
-25.28 to -11.68
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments Adjusted for Baseline value
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value -19.24
Confidence Interval (2-Sided) 95%
-23.20 to -15.28
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments Adjusted for Baseline value
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value -18.37
Confidence Interval (2-Sided) 95%
-24.39 to -12.35
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments Adjusted for Baseline value
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value -17.15
Confidence Interval (2-Sided) 95%
-23.23 to -11.08
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
16.Secondary Outcome
Title Percent Change From Baseline in Lipoprotein (a) at Week 12
Hide Description [Not Specified]
Time Frame Baseline and Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
Overall Number of Participants Analyzed 76 78 77 77 153 153
Median (Inter-Quartile Range)
Unit of Measure: percent change
0.00
(-8.51 to 17.50)
0.00
(-10.53 to 8.11)
0.00
(-9.09 to 12.50)
-2.05
(-17.19 to 8.33)
-20.41
(-39.53 to 0.00)
-17.82
(-38.46 to 0.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments Adjusted for Baseline value
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value -20.41
Confidence Interval (2-Sided) 95%
-27.76 to -13.06
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments Adjusted for Baseline value
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value -17.82
Confidence Interval (2-Sided) 95%
-24.51 to -11.12
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments Adjusted for Baseline value
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value -20.41
Confidence Interval (2-Sided) 95%
-28.13 to -12.69
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments Adjusted for Baseline value
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value -15.77
Confidence Interval (2-Sided) 95%
-24.39 to -7.14
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
17.Secondary Outcome
Title Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12
Hide Description [Not Specified]
Time Frame Baseline and Weeks 10 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
Overall Number of Participants Analyzed 76 78 77 77 153 153
Median (Inter-Quartile Range)
Unit of Measure: percent change
-3.89
(-18.85 to 11.24)
4.89
(-12.71 to 31.65)
-1.46
(-15.03 to 18.41)
-3.97
(-17.65 to 10.38)
-9.16
(-24.19 to 11.03)
-15.71
(-28.20 to 6.40)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.72
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments Adjusted for Baseline value
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value -5.27
Confidence Interval (2-Sided) 95%
-13.27 to 2.73
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments Adjusted for Baseline value
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value -20.59
Confidence Interval (2-Sided) 95%
-30.98 to -10.20
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.027
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments Adjusted for Baseline value
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value -7.71
Confidence Interval (2-Sided) 95%
-16.86 to 1.45
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.044
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments Adjusted for Baseline value
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value -11.73
Confidence Interval (2-Sided) 95%
-21.19 to -2.27
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
18.Secondary Outcome
Title Percent Change From Baseline in Triglycerides at Week 12
Hide Description [Not Specified]
Time Frame Baseline and Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
Overall Number of Participants Analyzed 76 78 77 77 153 153
Median (Inter-Quartile Range)
Unit of Measure: percent change
-1.91
(-18.58 to 11.46)
2.01
(-16.62 to 33.83)
0.00
(-13.26 to 17.54)
-2.41
(-19.34 to 12.86)
-8.14
(-26.14 to 10.13)
-15.64
(-30.03 to 1.53)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.72
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments Adjusted for Baseline value
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value -6.23
Confidence Interval (2-Sided) 95%
-16.41 to 3.95
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments Adjusted for Baseline value
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value -17.65
Confidence Interval (2-Sided) 95%
-26.67 to -8.63
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.027
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments Adjusted for Baseline value
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value -8.14
Confidence Interval (2-Sided) 95%
-17.54 to 1.26
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.044
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments Adjusted for Baseline value
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value -13.23
Confidence Interval (2-Sided) 95%
-21.69 to -4.77
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
19.Secondary Outcome
Title Percent Change From Baseline in Very Low Density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12
Hide Description [Not Specified]
Time Frame Baseline and Weeks 10 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
Overall Number of Participants Analyzed 76 78 77 77 153 153
Median (Inter-Quartile Range)
Unit of Measure: percent change
-3.81
(-19.16 to 9.97)
4.22
(-13.60 to 27.91)
-2.69
(-16.54 to 16.67)
-3.33
(-20.00 to 9.52)
-8.40
(-25.43 to 10.91)
-16.17
(-28.00 to 5.52)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.072
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments Adjusted for Baseline value
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value -4.59
Confidence Interval (2-Sided) 95%
-11.30 to 2.12
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments Adjusted for Baseline value
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value -20.39
Confidence Interval (2-Sided) 95%
-30.11 to -10.68
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.082
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments Adjusted for Baseline value
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value -5.71
Confidence Interval (2-Sided) 95%
-14.13 to 2.71
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.044
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments Adjusted for Baselie value
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value -12.84
Confidence Interval (2-Sided) 95%
-22.14 to -3.54
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
20.Secondary Outcome
Title Percent Change From Baseline in VLDL-C at Week 12
Hide Description [Not Specified]
Time Frame Baseline and Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Ful analysis set
Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
Overall Number of Participants Analyzed 76 78 77 77 153 153
Median (Inter-Quartile Range)
Unit of Measure: percent change
-1.58
(-20.00 to 10.53)
0.00
(-16.67 to 33.33)
-0.94
(-12.32 to 12.93)
-3.61
(-19.23 to 14.29)
-9.52
(-26.83 to 10.34)
-16.33
(-30.73 to 2.51)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.72
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments Adjusted for Baseline value
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value -7.94
Confidence Interval (2-Sided) 95%
-18.81 to 2.92
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments Adjusted for Baseline value
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value -16.33
Confidence Interval (2-Sided) 95%
-25.64 to -7.02
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.082
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments Adjusted for Baseline value
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value -8.58
Confidence Interval (2-Sided) 95%
-18.10 to 0.94
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.044
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit as covariates.
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value -12.72
Confidence Interval (2-Sided) 95%
-20.89 to -4.54
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
21.Secondary Outcome
Title Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at the Mean of Weeks 10 and 12
Hide Description [Not Specified]
Time Frame Baseline and Weeks 10 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
Overall Number of Participants Analyzed 76 78 77 77 153 153
Median (Inter-Quartile Range)
Unit of Measure: percent change
-1.64
(-8.41 to 5.03)
-4.67
(-10.63 to -0.57)
-0.92
(-10.11 to 7.29)
0.00
(-6.98 to 8.68)
3.89
(-1.35 to 11.55)
3.81
(-2.56 to 11.86)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments Adjusted for Baseline value
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value 5.53
Confidence Interval (2-Sided) 95%
2.23 to 8.84
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments Adjusted for Baseline value
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value 8.48
Confidence Interval (2-Sided) 95%
5.53 to 11.43
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.013
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments Adjusted for Baseline value
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value 4.81
Confidence Interval (2-Sided) 95%
0.85 to 8.78
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.044
Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
Method Quade test
Comments Adjusted for Baseline visit
Method of Estimation Estimation Parameter Median Treatment Difference
Estimated Value 3.81
Confidence Interval (2-Sided) 95%
-0.77 to 8.39
Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
22.Secondary Outcome
Title Percent Change From Baseline in HDL-C at Week 12
Hide Description [Not Specified]
Time Frame Baseline and Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM