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Reduction of LDL-C With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study-2 (RUTHERFORD-2)

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ClinicalTrials.gov Identifier: NCT01763918
Recruitment Status : Completed
First Posted : January 9, 2013
Results First Posted : December 22, 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: Placebo
Enrollment 331
Recruitment Details Men and women 18 to 80 years old with a diagnosis of heterozygous familial hypercholesterolemia (HeFH) on stable doses of an approved statin with fasting low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL were eligible for this study. The first participant enrolled on 07 February 2013 and the last participant enrolled 03 September 2013.
Pre-assignment Details Participants received subcutaneous placebo corresponding to the once monthly dose volume during a 6-week screening period. Those who completed the screening period and met final eligibility criteria were randomized 1:1:2:2 into 4 treatment groups. Randomization was stratified by LDL-C level (< 160 mg/dL vs ≥ 160 mg/dL) and ezetimibe use.
Arm/Group Title Placebo Q2W Placebo QM Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Period Title: Overall Study
Started 55 55 111 110
Received Treatment 54 55 110 110
Completed 49 54 101 108
Not Completed 6 1 10 2
Reason Not Completed
Withdrawal by Subject             2             1             1             2
Sponsor Decision             4             0             9             0
Arm/Group Title Placebo Q2W Placebo QM Evolocumab Q2W Evolocumab QM Total
Hide Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Total of all reporting groups
Overall Number of Baseline Participants 55 55 111 110 331
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 55 participants 55 participants 111 participants 110 participants 331 participants
51.1  (14.1) 46.8  (12.1) 52.3  (12.6) 51.9  (12.0) 51.1  (12.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants 55 participants 111 participants 110 participants 331 participants
Female
25
  45.5%
24
  43.6%
45
  40.5%
46
  41.8%
140
  42.3%
Male
30
  54.5%
31
  56.4%
66
  59.5%
64
  58.2%
191
  57.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 55 participants 55 participants 111 participants 110 participants 331 participants
American Indian or Alaska Native 0 0 0 0 0
Asian 1 3 4 8 16
Black or African American 1 0 1 1 3
Native Hawaiian or Other Pacific Islander 0 0 0 0 0
White 51 49 100 98 298
Other 2 3 6 3 14
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 55 participants 55 participants 111 participants 110 participants 331 participants
Hispanic or Latino 1 0 0 1 2
Not Hispanic or Latino 54 55 111 109 329
Stratification Factor: Low-Density Lipoprotein Cholesterol (LDL-C) Level  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 55 participants 55 participants 111 participants 110 participants 331 participants
< 160 mg/dL 35 35 70 70 210
≥ 160 mg/dL 20 20 41 40 121
Baseline Ezetimibe Use  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 55 participants 55 participants 111 participants 110 participants 331 participants
No 22 21 43 43 129
Yes 33 34 68 67 202
LDL-C Concentration   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 55 participants 55 participants 111 participants 110 participants 331 participants
151.1  (36.5) 151.5  (42.5) 161.4  (51.0) 153.6  (43.3) 155.5  (44.9)
[1]
Measure Description:

Data are provided for the full analysis set (all randomized participants who received at least

1 dose of investigational product)

Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Concentration   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 55 participants 55 participants 111 participants 110 participants 331 participants
175.4  (43.9) 175.4  (45.9) 187.4  (56.7) 178.5  (45.8) 180.4  (49.5)
[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 55 participants 55 participants 111 participants 110 participants 331 participants
114.3  (29.8) 110.3  (21.7) 119.0  (30.7) 114.9  (25.5) 115.4  (27.5)
[1]
Measure Description: Data are provided for the full analysis set
Total cholesterol/HDL-C Ratio   [1] 
Mean (Standard Deviation)
Unit of measure:  Ratio
Number Analyzed 55 participants 55 participants 111 participants 110 participants 331 participants
4.695  (1.905) 4.844  (1.435) 5.159  (2.031) 4.842  (1.801) 4.924  (1.845)
[1]
Measure Description: Data are provided for the full analysis set
Apolipoprotein B/Apolipoprotein A1 Ratio   [1] 
Mean (Standard Deviation)
Unit of measure:  Ratio
Number Analyzed 55 participants 55 participants 111 participants 110 participants 331 participants
0.815  (0.264) 0.851  (0.249) 0.888  (0.322) 0.850  (0.331) 0.857  (0.305)
[1]
Measure Description: Data are provided for the full analysis set
Lipoprotein(a) Concentration   [1] 
Median (Inter-Quartile Range)
Unit of measure:  nmol/L
Number Analyzed 55 participants 55 participants 111 participants 110 participants 331 participants
44.0
(24.0 to 105.0)
87.0
(36.0 to 219.0)
77.5
(29.0 to 205.5)
61.0
(17.0 to 194.0)
65.0
(25.0 to 199.0)
[1]
Measure Description: Data are provided for the full analysis set
Triglyceride Concentration   [1] 
Median (Inter-Quartile Range)
Unit of measure:  mg/dL
Number Analyzed 55 participants 55 participants 111 participants 110 participants 331 participants
95.8
(74.5 to 143.0)
102.0
(79.0 to 151.0)
118.5
(86.5 to 160.5)
112.5
(84.5 to 156.5)
110.0
(81.5 to 154.0)
[1]
Measure Description: Data are provided for the full analysis set
Very Low-Density Lipoprotein Cholesterol (VLDL-C) Concentration   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 55 participants 55 participants 111 participants 110 participants 331 participants
23.1  (10.7) 23.9  (10.5) 25.9  (11.8) 24.9  (11.7) 24.8  (11.4)
[1]
Measure Description: Data are provided for the full analysis set
HDL-C Concentration   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 55 participants 55 participants 111 participants 110 participants 331 participants
53.2  (16.5) 49.1  (12.7) 50.4  (16.1) 51.9  (16.0) 51.1  (15.6)
[1]
Measure Description: Data are provided for the full analysis set
1.Primary Outcome
Title Percent 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. Least squares (LS) means are from a repeated measures linear effects model; missing values were not imputed.
Arm/Group Title Placebo Q2W Placebo QM Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Overall Number of Participants Analyzed 54 55 110 110
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-2.02  (2.49) 5.53  (3.25) -61.25  (1.77) -55.74  (2.25)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
Comments Within each dose frequency, the null hypothesis was that there was no mean difference in the percent change from baseline at week 12 or 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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -59.23
Confidence Interval (2-Sided) 95%
-65.11 to -53.35
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.98
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
Comments Within each dose frequency, the null hypothesis was that there was no mean difference in the percent change from baseline at week 12 or 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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -61.27
Confidence Interval (2-Sided) 95%
-69.00 to -53.55
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.91
Estimation Comments [Not Specified]
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 Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Overall Number of Participants Analyzed 54 55 110 110
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-1.08  (2.41) 2.30  (2.41) -61.23  (1.71) -63.25  (1.70)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
Comments Within each dose frequency, the null hypothesis was that there was no mean difference in the percent change from baseline at week 12 or 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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -60.15
Confidence Interval (2-Sided) 95%
-65.83 to -54.46
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.88
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
Comments Within each dose frequency, the null hypothesis was that there was no mean difference in the percent change from baseline at week 12 or 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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -65.55
Confidence Interval (2-Sided) 95%
-71.27 to -59.83
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.90
Estimation Comments [Not Specified]
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 Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Overall Number of Participants Analyzed 54 55 110 110
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-6.5  (4.2) -1.3  (4.1) -101.7  (3.0) -98.8  (2.9)
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 Repeated measures linear effects model
Comments The model includes treatment group, baseline LDL-C and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -95.2
Confidence Interval (2-Sided) 95%
-105.1 to -85.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.0
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 Repeated measures linear effects model
Comments The model includes treatment group, baseline LDL-C and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -97.4
Confidence Interval (2-Sided) 95%
-107.1 to -87.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.9
Estimation Comments [Not Specified]
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 Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Overall Number of Participants Analyzed 54 55 110 110
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-8.5  (4.2) 4.1  (5.2) -101.3  (3.0) -87.2  (3.6)
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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -92.9
Confidence Interval (2-Sided) 95%
-102.9 to -82.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.1
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 Repeated measures linear effects model
Comments The model includes treatment group, baseline LDL-C and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -91.3
Confidence Interval (2-Sided) 95%
-103.8 to -78.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.3
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L)
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 Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Overall Number of Participants Analyzed 54 55 110 110
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
1.9
(0.3 to 9.9)
1.9
(0.3 to 9.8)
67.0
(57.7 to 75.1)
80.4
(71.9 to 86.8)
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 Cochran-Mantel Haenszel test stratified by baseline LDL-C and ezetimibe use.
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 65.1
Confidence Interval (2-Sided) 95%
52.8 to 73.4
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 Cochran-Mantel Haenszel test stratified by baseline LDL-C and ezetimibe use.
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 78.5
Confidence Interval (2-Sided) 95%
66.9 to 85.1
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) 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 Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Overall Number of Participants Analyzed 54 55 110 110
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
2.0
(0.3 to 10.3)
2.2
(0.4 to 11.3)
68.3
(58.8 to 76.4)
63.1
(53.5 to 71.8)
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 Cochran-Mantel Haenszel test stratified by baseline LDL-C and ezetimibe use
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 66.3
Confidence Interval (2-Sided) 95%
53.7 to 74.6
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 Cochran-Mantel Haenszel test stratified by baseline LDL-C and ezetimibe use.
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 60.9
Confidence Interval (2-Sided) 95%
47.6 to 69.8
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 Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Overall Number of Participants Analyzed 54 55 110 110
Least Squares Mean (Standard Error)
Unit of Measure: percent change
0.21  (2.29) 2.72  (2.21) -55.79  (1.63) -57.28  (1.56)
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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -56.00
Confidence Interval (2-Sided) 95%
-61.41 to -50.59
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.74
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 Repeated measures linear effects model
Comments The model includes treatment group, baseline LDL-C and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -60.01
Confidence Interval (2-Sided) 95%
-65.24 to -54.77
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.65
Estimation Comments [Not Specified]
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 Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Overall Number of Participants Analyzed 54 55 110 110
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-1.39  (2.40) 5.29  (2.94) -56.19  (1.71) -49.67  (2.04)
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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -54.79
Confidence Interval (2-Sided) 95%
-60.47 to -49.12
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.87
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 Repeated measures linear effects model
Comments The model includes treatment group, baseline LDL-C and ezetimibe use, 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%
-61.95 to -47.96
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.54
Estimation Comments [Not Specified]
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 Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Overall Number of Participants Analyzed 54 55 110 110
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-0.19  (2.10) 2.21  (1.97) -49.58  (1.48) -52.76  (1.36)
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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -49.39
Confidence Interval (2-Sided) 95%
-54.32 to -44.46
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.50
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 Repeated measures linear effects model
Comments The model includes treatment group, baseline LDL-C and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -54.98
Confidence Interval (2-Sided) 95%
-59.58 to -50.38
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.33
Estimation Comments [Not Specified]
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 Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Overall Number of Participants Analyzed 54 55 110 110
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-0.67  (2.32) 4.60  (2.70) -49.75  (1.63) -44.81  (1.80)
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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -49.09
Confidence Interval (2-Sided) 95%
-54.55 to -43.63
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.76
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 Repeated measures linear effects model
Comments The model includes treatment group, baseline LDL-C and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -49.41
Confidence Interval (2-Sided) 95%
-55.73 to -43.10
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.19
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Percent Change From Baseline in the Total Cholesterol/HDL-C 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 Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Overall Number of Participants Analyzed 54 55 110 110
Least Squares Mean (Standard Error)
Unit of Measure: percent change
0.86  (2.05) 4.14  (2.13) -45.74  (1.45) -45.02  (1.50)
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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -46.59
Confidence Interval (2-Sided) 95%
-51.43 to -41.76
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.45
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 Repeated measures linear effects model
Comments The model includes treatment group, baseline LDL-C and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -49.16
Confidence Interval (2-Sided) 95%
-54.21 to -44.11
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.56
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Percent Change From Baseline in the Total Cholesterol/HDL-C 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 Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Overall Number of Participants Analyzed 54 55 110 110
Least Squares Mean (Standard Error)
Unit of Measure: percent change
0.12  (2.19) 7.11  (3.13) -45.95  (1.56) -38.32  (2.15)
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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -46.08
Confidence Interval (2-Sided) 95%
-51.27 to -40.88
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.63
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 Repeated measures linear effects model
Comments The model includes treatment group, baseline LDL-C and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -45.42
Confidence Interval (2-Sided) 95%
-52.86 to -37.98
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.77
Estimation Comments [Not Specified]
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 Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Overall Number of Participants Analyzed 54 55 110 110
Least Squares Mean (Standard Error)
Unit of Measure: percent change
0.78  (2.21) 1.65  (2.35) -52.39  (1.56) -53.91  (1.60)
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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -53.17
Confidence Interval (2-Sided) 95%
-58.35 to -47.99
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.62
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 Repeated measures linear effects model
Comments The model includes treatment group, baseline LDL-C and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -55.56
Confidence Interval (2-Sided) 95%
-61.08 to -50.05
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.79
Estimation Comments [Not Specified]
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 Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Overall Number of Participants Analyzed 54 55 110 110
Least Squares Mean (Standard Error)
Unit of Measure: percent change
1.54  (2.49) 4.23  (3.66) -52.74  (1.75) -45.31  (2.42)
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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -54.28
Confidence Interval (2-Sided) 95%
-60.16 to -48.41
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.97
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 Repeated measures linear effects model
Comments The model includes treatment group, baseline LDL-C and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -49.55
Confidence Interval (2-Sided) 95%
-58.14 to -40.96
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.35
Estimation Comments [Not Specified]
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 Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Overall Number of Participants Analyzed 54 55 110 110
Least Squares Mean (Standard Error)
Unit of Measure: percent change
7.34  (2.97) 5.35  (2.95) -24.03  (2.09) -25.65  (2.07)
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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -31.37
Confidence Interval (2-Sided) 95%
-38.33 to -24.41
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.52
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 Repeated measures linear effects model
Comments The model includes treatment group, baseline LDL-C and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -31.00
Confidence Interval (2-Sided) 95%
-37.91 to -24.09
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.50
Estimation Comments [Not Specified]
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 Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Overall Number of Participants Analyzed 54 55 110 110
Least Squares Mean (Standard Error)
Unit of Measure: percent change
8.68  (3.27) 6.69  (3.16) -22.89  (2.31) -21.55  (2.17)
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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -31.57
Confidence Interval (2-Sided) 95%
-39.28 to -23.87
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.90
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 Repeated measures linear effects model
Comments The model includes treatment group, baseline LDL-C and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -28.24
Confidence Interval (2-Sided) 95%
-35.61 to -20.88
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.73
Estimation Comments [Not Specified]
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 Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Overall Number of Participants Analyzed 54 55 110 110
Least Squares Mean (Standard Error)
Unit of Measure: percent change
9.09  (3.02) 7.49  (3.26) -13.27  (2.14) -9.25  (2.27)
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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -22.36
Confidence Interval (2-Sided) 95%
-29.48 to -15.24
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.60
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 Repeated measures linear effects model
Comments The model includes treatment group, baseline LDL-C and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -16.74
Confidence Interval (2-Sided) 95%
-24.43 to -9.05
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.89
Estimation Comments [Not Specified]
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 Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Overall Number of Participants Analyzed 54 55 110 110
Least Squares Mean (Standard Error)
Unit of Measure: percent change
3.50  (3.51) 6.43  (4.15) -16.09  (2.49) -5.13  (2.84)
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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -19.59
Confidence Interval (2-Sided) 95%
-27.92 to -11.26
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.22
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 Repeated measures linear effects model
Comments The model includes treatment group, baseline LDL-C and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -11.56
Confidence Interval (2-Sided) 95%
-21.38 to -1.74
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.97
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Percent Change From Baseline in 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 Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Overall Number of Participants Analyzed 54 55 110 110
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-0.45  (1.70) -2.86  (1.84) 7.93  (1.20) 6.62  (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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value 8.38
Confidence Interval (2-Sided) 95%
4.36 to 12.40
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.04
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 Repeated measures linear effects model
Comments The model includes treatment group, baseline LDL-C and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value 9.48
Confidence Interval (2-Sided) 95%
5.10 to 13.85
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.21
Estimation Comments [Not Specified]
20.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 Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Overall Number of Participants Analyzed 54 55 110 110
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-1.15  (1.91) -3.73  (2.35) 8.05  (1.35) 5.35  (1.62)
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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value 9.20
Confidence Interval (2-Sided) 95%
4.66 to 13.74
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.30
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 Repeated measures linear effects model
Comments The model includes treatment group, baseline LDL-C and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value 9.07
Confidence Interval (2-Sided) 95%
3.48 to 1466
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.83
Estimation Comments [Not Specified]
21.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 Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Overall Number of Participants Analyzed 54 55 110 110
Least Squares Mean (Standard Error)
Unit of Measure: percent change
8.66  (2.90) 6.34  (3.27) -13.97  (2.06) -9.20  (2.27)
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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -22.63
Confidence Interval (2-Sided) 95%
-29.46 to -15.81
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.46
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 Repeated measures linear effects model
Comments The model includes treatment group, baseline LDL-C and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -15.54
Confidence Interval (2-Sided) 95%
-23.25 to -7.84
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.90
Estimation Comments [Not Specified]
22.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
Full analysis set
Arm/Group Title Placebo Q2W Placebo QM Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.
Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Overall Number of Participants Analyzed 54 55 110 110
Least Squares Mean (Standard Error)
Unit of Measure: percent change
3.73  (3.50) 4.10  (4.17) -17.25  (2.48) -5.06  (2.84)
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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -20.97
Confidence Interval (2-Sided) 95%
-29.29 to -12.66
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.21
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 Repeated measures linear effects model
Comments The model includes treatment group, baseline LDL-C and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -9.17
Confidence Interval (2-Sided) 95%
-19.01 to 0.68
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.98
Estimation Comments [Not Specified]
Time Frame From the first dose of blinded investigational product until the end of the study (up to 14 weeks).
Adverse Event Reporting Description Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
 
Arm/Group Title Placebo Q2W Placebo QM Evolocumab Q2W Evolocumab QM
Hide Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
All-Cause Mortality
Placebo Q2W Placebo QM Evolocumab Q2W Evolocumab QM
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Q2W Placebo QM Evolocumab Q2W Evolocumab QM
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/54 (3.70%)   3/55 (5.45%)   3/110 (2.73%)   4/110 (3.64%) 
Cardiac disorders         
Acute myocardial infarction  1  0/54 (0.00%)  0/55 (0.00%)  1/110 (0.91%)  0/110 (0.00%) 
Angina pectoris  1  0/54 (0.00%)  0/55 (0.00%)  1/110 (0.91%)  1/110 (0.91%) 
Coronary artery disease  1  1/54 (1.85%)  0/55 (0.00%)  0/110 (0.00%)  0/110 (0.00%) 
Gastrointestinal disorders         
Inguinal hernia  1  1/54 (1.85%)  0/55 (0.00%)  0/110 (0.00%)  0/110 (0.00%) 
Pancreatitis acute  1  0/54 (0.00%)  0/55 (0.00%)  0/110 (0.00%)  1/110 (0.91%) 
Investigations         
Blood creatine phosphokinase increased  1  0/54 (0.00%)  1/55 (1.82%)  0/110 (0.00%)  0/110 (0.00%) 
Colonoscopy abnormal  1  0/54 (0.00%)  0/55 (0.00%)  0/110 (0.00%)  1/110 (0.91%) 
Endoscopy gastrointestinal abnormal  1  0/54 (0.00%)  0/55 (0.00%)  0/110 (0.00%)  1/110 (0.91%) 
Nervous system disorders         
Epilepsy  1  0/54 (0.00%)  0/55 (0.00%)  0/110 (0.00%)  1/110 (0.91%) 
Psychiatric disorders         
Depression  1  0/54 (0.00%)  1/55 (1.82%)  0/110 (0.00%)  0/110 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Chronic obstructive pulmonary disease  1  0/54 (0.00%)  1/55 (1.82%)  0/110 (0.00%)  0/110 (0.00%) 
Skin and subcutaneous tissue disorders         
Erythema  1  0/54 (0.00%)  0/55 (0.00%)  1/110 (0.91%)  0/110 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Q2W Placebo QM Evolocumab Q2W Evolocumab QM
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/54 (9.26%)   10/55 (18.18%)   17/110 (15.45%)   24/110 (21.82%) 
Infections and infestations         
Nasopharyngitis  1  2/54 (3.70%)  3/55 (5.45%)  8/110 (7.27%)  11/110 (10.00%) 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  1/54 (1.85%)  1/55 (1.82%)  7/110 (6.36%)  1/110 (0.91%) 
Back pain  1  0/54 (0.00%)  1/55 (1.82%)  2/110 (1.82%)  6/110 (5.45%) 
Nervous system disorders         
Dizziness  1  1/54 (1.85%)  3/55 (5.45%)  0/110 (0.00%)  4/110 (3.64%) 
Headache  1  1/54 (1.85%)  3/55 (5.45%)  4/110 (3.64%)  5/110 (4.55%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
Name/Title: Study Director
Organization: Amgen Inc.
Phone: 866-572-6436
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01763918     History of Changes
Other Study ID Numbers: 20110117
2012-001365-32 ( EudraCT Number )
First Submitted: January 7, 2013
First Posted: January 9, 2013
Results First Submitted: September 2, 2015
Results First Posted: December 22, 2015
Last Update Posted: November 28, 2018