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LAPLACE-TIMI 57: Low-density Lipoprotein Cholesterol (LDL-C) Assessment With PCSK9 monoclonaL Antibody Inhibition Combined With Statin thErapy (LAPLACE)

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ClinicalTrials.gov Identifier: NCT01380730
Recruitment Status : Completed
First Posted : June 27, 2011
Results First Posted : October 1, 2015
Last Update Posted : November 2, 2018
Sponsor:
Collaborator:
TIMI Study Group
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
Other: Placebo to Evolocumab
Enrollment 631

Recruitment Details

This study enrolled adults aged 18 - 80 years who were on a statin, with or without ezetimibe, with stable dose(s) for at least 4 weeks, and fasting low-density lipoprotein cholesterol (LDL-C) ≥ 85 mg/dL.

The first patient enrolled on 18 July 2011 and the last patient enrolled on 22 December 2011.

Pre-assignment Details Eligible participants were randomized equally into 1 of 8 treatment groups. Randomization was stratified by screening LDL-C level (< 130 mg/dL or ≥ 130 mg/dL) and ezetimibe use at baseline (yes or no).
Arm/Group Title Placebo Q2W Placebo Q4W Evolocumab 70 mg Q2W Evolocumab 105 mg Q2W Evolocumab 140 mg Q2W Evolocumab 280 mg Q4W Evolocumab 350 mg Q4W Evolocumab 420 mg Q4W
Hide Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks. Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks. Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Period Title: Overall Study
Started 78 79 79 79 78 79 79 80
Received Treatment 78 77 [1] 79 79 78 79 79 80
Completed 78 79 79 79 77 79 79 80
Not Completed 0 0 0 0 1 0 0 0
Reason Not Completed
Death             0             0             0             0             1             0             0             0
[1]
2 participants did not receive treatment but were followed until the end of study
Arm/Group Title Placebo Q2W Placebo Q4W Evolocumab 70 mg Q2W Evolocumab 105 mg Q2W Evolocumab 140 mg Q2W Evolocumab 280 mg Q4W Evolocumab 350 mg Q4W Evolocumab 420 mg Q4W Total
Hide Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks. Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks. Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. Total of all reporting groups
Overall Number of Baseline Participants 78 77 79 79 78 79 79 80 629
Hide Baseline Analysis Population Description
Full analysis set (all randomized participants who received at least 1 dose of investigational product).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 78 participants 77 participants 79 participants 79 participants 78 participants 79 participants 79 participants 80 participants 629 participants
60.2  (8.8) 60.1  (9.6) 59.4  (9.9) 58.8  (9.7) 62.4  (10.2) 60.3  (8.4) 61.9  (8.8) 60.9  (10.3) 60.5  (9.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 78 participants 77 participants 79 participants 79 participants 78 participants 79 participants 79 participants 80 participants 629 participants
Female
42
  53.8%
41
  53.2%
44
  55.7%
25
  31.6%
45
  57.7%
40
  50.6%
38
  48.1%
44
  55.0%
319
  50.7%
Male
36
  46.2%
36
  46.8%
35
  44.3%
54
  68.4%
33
  42.3%
39
  49.4%
41
  51.9%
36
  45.0%
310
  49.3%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 78 participants 77 participants 79 participants 79 participants 78 participants 79 participants 79 participants 80 participants 629 participants
American Indian or Alaska Native 0 1 0 0 1 1 0 0 3
Asian 0 2 1 3 1 2 2 1 12
Black or African American 6 0 6 8 9 8 4 9 50
Native Hawaiian or Other Pacific Islander 0 0 0 1 0 2 0 0 3
White 72 74 72 67 67 64 72 70 558
Other 0 0 0 0 0 2 1 0 3
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 78 participants 77 participants 79 participants 79 participants 78 participants 79 participants 79 participants 80 participants 629 participants
Hispanic or Latino 1 6 5 0 6 1 0 2 21
Not Hispanic or Latino 77 71 74 79 72 78 79 78 608
Stratification Factor: LDL-C Level  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 78 participants 77 participants 79 participants 79 participants 78 participants 79 participants 79 participants 80 participants 629 participants
< 130 mg/dL 51 51 51 51 52 51 52 53 412
≥ 130 mg/dL 27 26 28 28 26 28 27 27 217
Stratification Factor: Baseline Ezetimibe Use  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 78 participants 77 participants 79 participants 79 participants 78 participants 79 participants 79 participants 80 participants 629 participants
No 71 69 72 72 71 72 72 73 572
Yes 7 8 7 7 7 7 7 7 57
LDL-C Concentration   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 78 participants 77 participants 79 participants 79 participants 78 participants 79 participants 79 participants 80 participants 629 participants
122.2  (27.1) 124.9  (30.6) 121.4  (24.4) 127.4  (32.1) 120.9  (25.1) 122.0  (28.8) 123.2  (27.1) 120.8  (26.5) 122.8  (27.7)
[1]
Measure Description: LDL-C was measured using ultracentrifugation.
Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Concentration  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 78 participants 77 participants 79 participants 79 participants 78 participants 79 participants 79 participants 80 participants 629 participants
146.9  (29.9) 150.2  (36.5) 145.3  (29.9) 151.2  (37.2) 145.3  (26.2) 146.3  (33.3) 150.0  (29.1) 144.4  (31.2) 147.4  (31.8)
Apolipoprotein B Concentration  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 78 participants 77 participants 79 participants 79 participants 78 participants 79 participants 79 participants 80 participants 629 participants
99.9  (17.0) 101.6  (20.0) 99.9  (16.8) 103.6  (22.3) 98.8  (16.6) 101.3  (21.2) 102.6  (18.9) 99.9  (18.6) 100.9  (19.0)
Total Cholesterol/HDL-C ratio  
Mean (Standard Deviation)
Unit of measure:  Ratio
Number Analyzed 78 participants 77 participants 79 participants 79 participants 78 participants 79 participants 79 participants 80 participants 629 participants
3.940  (1.016) 4.057  (1.303) 4.002  (1.243) 4.128  (1.473) 3.932  (1.022) 4.007  (1.300) 4.118  (0.963) 3.885  (1.090) 4.008  (1.184)
Apolipoprotein B/Apolipoprotein A-1 Ratio  
Mean (Standard Deviation)
Unit of measure:  Ratio
Number Analyzed 78 participants 77 participants 79 participants 79 participants 78 participants 79 participants 79 participants 80 participants 629 participants
0.660  (0.155) 0.676  (0.194) 0.675  (0.191) 0.695  (0.219) 0.649  (0.155) 0.662  (0.199) 0.687  (0.175) 0.653  (0.177) 0.670  (0.184)
1.Primary Outcome
Title Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
Hide Description LDL-C was measured using ultracentrifugation.
Time Frame Baseline and Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; missing ultracentrifugation LDL-C at Week 12 was imputed using last observation carried forward (LOCF) and calculated LDL-C.
Arm/Group Title Placebo Q2W Placebo Q4W Evolocumab 70 mg Q2W Evolocumab 105 mg Q2W Evolocumab 140 mg Q2W Evolocumab 280 mg Q4W Evolocumab 350 mg Q4W Evolocumab 420 mg Q4W
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks.
Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks.
Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Overall Number of Participants Analyzed 78 77 79 79 78 79 79 80
Least Squares Mean (Standard Error)
Unit of Measure: percent change
2.76  (2.39) -0.98  (2.51) -39.06  (2.39) -57.48  (2.39) -63.34  (2.40) -42.82  (2.52) -50.98  (2.51) -51.31  (2.53)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab 140 mg 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 ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -66.10
Confidence Interval (2-Sided) 95%
-71.48 to -60.72
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.73
Estimation Comments Placebo is the reference
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab 105 mg 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 ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -60.24
Confidence Interval (2-Sided) 95%
-65.61 to -54.88
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.73
Estimation Comments Placebo is the reference
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab 70 mg 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 ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -41.82
Confidence Interval (2-Sided) 95%
-47.18 to -36.45
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.73
Estimation Comments Placebo is the reference
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, Evolocumab 420 mg Q4W
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 ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -50.33
Confidence Interval (2-Sided) 95%
-56.04 to -44.62
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.90
Estimation Comments Placebo is the reference
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, Evolocumab 350 mg Q4W
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 ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -50.00
Confidence Interval (2-Sided) 95%
-55.69 to -44.31
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.89
Estimation Comments Placebo is the reference
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, Evolocumab 280 mg Q4W
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 ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -41.84
Confidence Interval (2-Sided) 95%
-47.55 to -36.13
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.90
Estimation Comments Placebo is the reference
2.Secondary Outcome
Title Change From Baseline in LDL-C at Week 12
Hide Description LDL-C was measured using ultracentrifugation.
Time Frame Baseline and Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; missing data at Week 12 were imputed using LOCF.
Arm/Group Title Placebo Q2W Placebo Q4W Evolocumab 70 mg Q2W Evolocumab 105 mg Q2W Evolocumab 140 mg Q2W Evolocumab 280 mg Q4W Evolocumab 350 mg Q4W Evolocumab 420 mg Q4W
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks.
Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks.
Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Overall Number of Participants Analyzed 78 77 79 79 78 79 79 80
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-0.2  (3.4) -3.2  (3.3) -50.9  (3.4) -77.6  (3.5) -79.5  (3.4) -53.7  (3.3) -64.3  (3.3) -64.3  (3.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab 140 mg Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -79.2
Confidence Interval (2-Sided) 95%
-87.0 to -71.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.0
Estimation Comments Placebo is the reference
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab 105 mg Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -77.4
Confidence Interval (2-Sided) 95%
-85.2 to -69.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.0
Estimation Comments Placebo is the reference
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab 70 mg Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -50.7
Confidence Interval (2-Sided) 95%
-58.5 to -43.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.0
Estimation Comments Placebo is the reference
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, Evolocumab 420 mg Q4W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -61.1
Confidence Interval (2-Sided) 95%
-68.6 to -53.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.8
Estimation Comments Placebo is the reference
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, Evolocumab 350 mg Q4W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -61.1
Confidence Interval (2-Sided) 95%
-68.5 to -53.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.8
Estimation Comments Placebo is the reference
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, Evolocumab 280 mg Q4W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -50.6
Confidence Interval (2-Sided) 95%
-58.0 to -43.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.8
Estimation Comments Placebo is the reference
3.Secondary Outcome
Title Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (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; missing data at Week 12 were imputed using LOCF.
Arm/Group Title Placebo Q2W Placebo Q4W Evolocumab 70 mg Q2W Evolocumab 105 mg Q2W Evolocumab 140 mg Q2W Evolocumab 280 mg Q4W Evolocumab 350 mg Q4W Evolocumab 420 mg Q4W
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks.
Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks.
Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Overall Number of Participants Analyzed 78 77 79 79 78 79 79 80
Least Squares Mean (Standard Error)
Unit of Measure: percent change
2.21  (2.20) -1.26  (2.26) -36.23  (2.20) -53.21  (2.20) -59.19  (2.21) -39.05  (2.27) -47.05  (2.26) -48.83  (2.27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab 140 mg Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -61.40
Confidence Interval (2-Sided) 95%
-66.37 to -56.43
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.53
Estimation Comments Placebo is the reference
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab 105 mg Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -55.42
Confidence Interval (2-Sided) 95%
-60.37 to -50.47
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.52
Estimation Comments Placebo is the reference
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab 70 mg Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -38.44
Confidence Interval (2-Sided) 95%
-43.39 to -33.48
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.52
Estimation Comments Placebo is the reference
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, Evolocumab 420 mg Q4W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -47.58
Confidence Interval (2-Sided) 95%
-52.72 to -42.44
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.61
Estimation Comments Placebo is the reference
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, Evolocumab 350 mg Q4W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -45.80
Confidence Interval (2-Sided) 95%
-50.92 to -40.67
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.60
Estimation Comments Placebo is the reference
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, Evolocumab 280 mg Q4W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -37.79
Confidence Interval (2-Sided) 95%
-42.94 to -32.65
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.61
Estimation Comments Placebo is the reference
4.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; missing data at Week 12 were imputed using LOCF.
Arm/Group Title Placebo Q2W Placebo Q4W Evolocumab 70 mg Q2W Evolocumab 105 mg Q2W Evolocumab 140 mg Q2W Evolocumab 280 mg Q4W Evolocumab 350 mg Q4W Evolocumab 420 mg Q4W
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks.
Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks.
Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Overall Number of Participants Analyzed 78 77 79 79 78 79 79 80
Least Squares Mean (Standard Error)
Unit of Measure: percent change
5.86  (2.15) 3.22  (2.25) -28.88  (2.15) -44.29  (2.14) -50.59  (2.15) -31.16  (2.26) -37.55  (2.26) -38.81  (2.27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab 140 mg Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -56.45
Confidence Interval (2-Sided) 95%
-61.28 to -51.61
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.46
Estimation Comments Placebo is the reference
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab 105 mg Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -50.15
Confidence Interval (2-Sided) 95%
-54.97 to -45.33
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.45
Estimation Comments Placebo is the reference
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab 70 mg Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -34.74
Confidence Interval (2-Sided) 95%
-39.56 to -29.92
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.45
Estimation Comments Placebo is the reference
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, Evolocumab 420 mg Q4W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -42.03
Confidence Interval (2-Sided) 95%
-47.16 to -36.90
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.61
Estimation Comments Placebo is the reference
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, Evolocumab 350 mg Q4W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -40.77
Confidence Interval (2-Sided) 95%
-45.88 to -35.66
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.60
Estimation Comments Placebo is the reference
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, Evolocumab 280 mg Q4W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -34.38
Confidence Interval (2-Sided) 95%
-39.51 to -29.25
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.61
Estimation Comments Placebo is the reference
5.Secondary Outcome
Title Percent Change From Baseline in 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; missing data at Week 12 were imputed using LOCF.
Arm/Group Title Placebo Q2W Placebo Q4W Evolocumab 70 mg Q2W Evolocumab 105 mg Q2W Evolocumab 140 mg Q2W Evolocumab 280 mg Q4W Evolocumab 350 mg Q4W Evolocumab 420 mg Q4W
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks.
Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks.
Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Overall Number of Participants Analyzed 78 77 79 79 78 79 79 80
Least Squares Mean (Standard Error)
Unit of Measure: percent change
2.64  (1.97) -2.00  (1.90) -28.76  (1.97) -40.73  (1.97) -45.09  (1.98) -29.73  (1.91) -37.97  (1.91) -37.66  (1.92)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab 140 mg Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -47.74
Confidence Interval (2-Sided) 95%
-52.18 to -43.29
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.26
Estimation Comments Placebo is the reference
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab 105 mg Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -43.38
Confidence Interval (2-Sided) 95%
-47.81 to -38.94
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.25
Estimation Comments Placebo is the reference
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab 70 mg Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -31.40
Confidence Interval (2-Sided) 95%
-35.83 to -26.97
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.25
Estimation Comments Placebo is the reference
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, Evolocumab 420 mg Q4W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -35.65
Confidence Interval (2-Sided) 95%
-39.99 to -31.32
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.20
Estimation Comments Placebo is the reference
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, Evolocumab 350 mg Q4W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -35.97
Confidence Interval (2-Sided) 95%
-40.29 to -31.65
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.20
Estimation Comments Placebo is the reference
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, Evolocumab 280 mg Q4W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -27.73
Confidence Interval (2-Sided) 95%
-32.06 to -23.39
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.20
Estimation Comments Placebo is the reference
6.Secondary Outcome
Title Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 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; missing data at Week 12 were imputed using LOCF.
Arm/Group Title Placebo Q2W Placebo Q4W Evolocumab 70 mg Q2W Evolocumab 105 mg Q2W Evolocumab 140 mg Q2W Evolocumab 280 mg Q4W Evolocumab 350 mg Q4W Evolocumab 420 mg Q4W
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks.
Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks.
Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Overall Number of Participants Analyzed 78 77 79 79 78 79 79 80
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-0.30  (2.13) -0.35  (2.38) -35.04  (2.13) -47.60  (2.12) -53.73  (2.14) -34.11  (2.40) -42.74  (2.39) -43.28  (2.40)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab 140 mg Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -53.44
Confidence Interval (2-Sided) 95%
-58.23 to -48.65
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.44
Estimation Comments Placebo is the reference
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab 105 mg Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -47.30
Confidence Interval (2-Sided) 95%
-52.08 to -42.52
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.43
Estimation Comments Placebo is the reference
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab 70 mg Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -34.75
Confidence Interval (2-Sided) 95%
-39.53 to -29.97
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.43
Estimation Comments Placebo is the reference
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, Evolocumab 420 mg Q4W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -42.93
Confidence Interval (2-Sided) 95%
-48.36 to -37.50
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.76
Estimation Comments Placebo is the reference
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, Evolocumab 350 mg Q4W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -42.40
Confidence Interval (2-Sided) 95%
-47.81 to -36.98
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.75
Estimation Comments Placebo is the reference
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, Evolocumab 280 mg Q4W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Testing based on a significance level of 0.05.
Method ANCOVA
Comments The ANCOVA model included treatment group and stratification factors.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -33.77
Confidence Interval (2-Sided) 95%
-39.20 to -28.33
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.76
Estimation Comments Placebo is the reference
Time Frame 12 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 Q4W Evolocumab 70 mg Q2W Evolocumab 105 mg Q2W Evolocumab 140 mg Q2W Evolocumab 280 mg Q4W Evolocumab 350 mg Q4W Evolocumab 420 mg Q4W
Hide Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks. Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks. Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
All-Cause Mortality
Placebo Q2W Placebo Q4W Evolocumab 70 mg Q2W Evolocumab 105 mg Q2W Evolocumab 140 mg Q2W Evolocumab 280 mg Q4W Evolocumab 350 mg Q4W Evolocumab 420 mg Q4W
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Q2W Placebo Q4W Evolocumab 70 mg Q2W Evolocumab 105 mg Q2W Evolocumab 140 mg Q2W Evolocumab 280 mg Q4W Evolocumab 350 mg Q4W Evolocumab 420 mg Q4W
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/78 (5.13%)   0/77 (0.00%)   0/79 (0.00%)   1/79 (1.27%)   4/78 (5.13%)   2/79 (2.53%)   2/79 (2.53%)   2/80 (2.50%) 
Blood and lymphatic system disorders                 
Anaemia  1  0/78 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  1/78 (1.28%)  0/79 (0.00%)  0/79 (0.00%)  0/80 (0.00%) 
Cardiac disorders                 
Atrial fibrillation  1  0/78 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  0/78 (0.00%)  1/79 (1.27%)  0/79 (0.00%)  0/80 (0.00%) 
Cardiac failure congestive  1  0/78 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  1/78 (1.28%)  0/79 (0.00%)  0/79 (0.00%)  0/80 (0.00%) 
Coronary artery disease  1  0/78 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  1/78 (1.28%)  0/79 (0.00%)  0/79 (0.00%)  0/80 (0.00%) 
Tachycardia  1  0/78 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  1/78 (1.28%)  0/79 (0.00%)  0/79 (0.00%)  0/80 (0.00%) 
General disorders                 
Pain  1  0/78 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  1/78 (1.28%)  0/79 (0.00%)  0/79 (0.00%)  0/80 (0.00%) 
Hepatobiliary disorders                 
Cholecystitis acute  1  1/78 (1.28%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  0/78 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  0/80 (0.00%) 
Infections and infestations                 
Cellulitis  1  0/78 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  1/78 (1.28%)  0/79 (0.00%)  1/79 (1.27%)  0/80 (0.00%) 
Pneumonia  1  0/78 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  1/78 (1.28%)  0/79 (0.00%)  1/79 (1.27%)  0/80 (0.00%) 
Urinary tract infection  1  1/78 (1.28%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  0/78 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  0/80 (0.00%) 
Injury, poisoning and procedural complications                 
Acetabulum fracture  1  0/78 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  1/78 (1.28%)  0/79 (0.00%)  0/79 (0.00%)  0/80 (0.00%) 
Cervical vertebral fracture  1  0/78 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  0/78 (0.00%)  1/79 (1.27%)  0/79 (0.00%)  0/80 (0.00%) 
Contusion  1  0/78 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  1/78 (1.28%)  0/79 (0.00%)  0/79 (0.00%)  0/80 (0.00%) 
Hand fracture  1  0/78 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  0/78 (0.00%)  1/79 (1.27%)  0/79 (0.00%)  0/80 (0.00%) 
Joint dislocation  1  0/78 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  1/78 (1.28%)  0/79 (0.00%)  0/79 (0.00%)  0/80 (0.00%) 
Laceration  1  0/78 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  0/78 (0.00%)  1/79 (1.27%)  0/79 (0.00%)  0/80 (0.00%) 
Multiple injuries  1  0/78 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  1/78 (1.28%)  0/79 (0.00%)  0/79 (0.00%)  0/80 (0.00%) 
Rib fracture  1  0/78 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  1/78 (1.28%)  0/79 (0.00%)  0/79 (0.00%)  0/80 (0.00%) 
Road traffic accident  1  0/78 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  1/78 (1.28%)  0/79 (0.00%)  0/79 (0.00%)  0/80 (0.00%) 
Metabolism and nutrition disorders                 
Hypomagnesaemia  1  0/78 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  1/78 (1.28%)  0/79 (0.00%)  0/79 (0.00%)  0/80 (0.00%) 
Musculoskeletal and connective tissue disorders                 
Arthralgia  1  0/78 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  0/78 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  1/80 (1.25%) 
Spondylolisthesis  1  0/78 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  0/78 (0.00%)  0/79 (0.00%)  1/79 (1.27%)  0/80 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                 
Bladder cancer  1  1/78 (1.28%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  0/78 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  0/80 (0.00%) 
Nervous system disorders                 
Neurological symptom  1  0/78 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  1/78 (1.28%)  0/79 (0.00%)  0/79 (0.00%)  0/80 (0.00%) 
Syncope  1  1/78 (1.28%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  0/78 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  0/80 (0.00%) 
Psychiatric disorders                 
Alcohol withdrawal syndrome  1  0/78 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  1/78 (1.28%)  0/79 (0.00%)  0/79 (0.00%)  0/80 (0.00%) 
Delirium  1  0/78 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  1/78 (1.28%)  0/79 (0.00%)  0/79 (0.00%)  0/80 (0.00%) 
Substance abuse  1  0/78 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  1/78 (1.28%)  0/79 (0.00%)  0/79 (0.00%)  0/80 (0.00%) 
Reproductive system and breast disorders                 
Penile haemorrhage  1  0/78 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  0/78 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  1/80 (1.25%) 
Respiratory, thoracic and mediastinal disorders                 
Chronic obstructive pulmonary disease  1  1/78 (1.28%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  0/78 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  0/80 (0.00%) 
Pulmonary embolism  1  0/78 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  1/79 (1.27%)  0/78 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  0/80 (0.00%) 
Social circumstances                 
Physical assault  1  0/78 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  1/78 (1.28%)  0/79 (0.00%)  0/79 (0.00%)  0/80 (0.00%) 
Surgical and medical procedures                 
Coronary artery bypass  1  1/78 (1.28%)  0/77 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  0/78 (0.00%)  0/79 (0.00%)  0/79 (0.00%)  0/80 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
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 Q4W Evolocumab 70 mg Q2W Evolocumab 105 mg Q2W Evolocumab 140 mg Q2W Evolocumab 280 mg Q4W Evolocumab 350 mg Q4W Evolocumab 420 mg Q4W
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   15/78 (19.23%)   17/77 (22.08%)   20/79 (25.32%)   28/79 (35.44%)   27/78 (34.62%)   21/79 (26.58%)   23/79 (29.11%)   30/80 (37.50%) 
Gastrointestinal disorders                 
Diarrhoea  1  2/78 (2.56%)  2/77 (2.60%)  1/79 (1.27%)  4/79 (5.06%)  2/78 (2.56%)  1/79 (1.27%)  2/79 (2.53%)  3/80 (3.75%) 
Nausea  1  1/78 (1.28%)  0/77 (0.00%)  0/79 (0.00%)  1/79 (1.27%)  3/78 (3.85%)  4/79 (5.06%)  3/79 (3.80%)  4/80 (5.00%) 
General disorders                 
Fatigue  1  1/78 (1.28%)  0/77 (0.00%)  0/79 (0.00%)  1/79 (1.27%)  1/78 (1.28%)  0/79 (0.00%)  2/79 (2.53%)  5/80 (6.25%) 
Infections and infestations                 
Influenza  1  2/78 (2.56%)  1/77 (1.30%)  3/79 (3.80%)  3/79 (3.80%)  6/78 (7.69%)  0/79 (0.00%)  1/79 (1.27%)  0/80 (0.00%) 
Nasopharyngitis  1  6/78 (7.69%)  5/77 (6.49%)  9/79 (11.39%)  8/79 (10.13%)  7/78 (8.97%)  8/79 (10.13%)  8/79 (10.13%)  8/80 (10.00%) 
Upper respiratory tract infection  1  2/78 (2.56%)  2/77 (2.60%)  2/79 (2.53%)  3/79 (3.80%)  4/78 (5.13%)  0/79 (0.00%)  0/79 (0.00%)  4/80 (5.00%) 
Musculoskeletal and connective tissue disorders                 
Arthralgia  1  0/78 (0.00%)  3/77 (3.90%)  4/79 (5.06%)  5/79 (6.33%)  2/78 (2.56%)  0/79 (0.00%)  1/79 (1.27%)  1/80 (1.25%) 
Back pain  1  1/78 (1.28%)  1/77 (1.30%)  0/79 (0.00%)  2/79 (2.53%)  2/78 (2.56%)  4/79 (5.06%)  3/79 (3.80%)  3/80 (3.75%) 
Myalgia  1  0/78 (0.00%)  2/77 (2.60%)  2/79 (2.53%)  1/79 (1.27%)  1/78 (1.28%)  1/79 (1.27%)  4/79 (5.06%)  0/80 (0.00%) 
Nervous system disorders                 
Dizziness  1  1/78 (1.28%)  1/77 (1.30%)  0/79 (0.00%)  0/79 (0.00%)  0/78 (0.00%)  0/79 (0.00%)  4/79 (5.06%)  1/80 (1.25%) 
Headache  1  2/78 (2.56%)  0/77 (0.00%)  1/79 (1.27%)  1/79 (1.27%)  4/78 (5.13%)  1/79 (1.27%)  2/79 (2.53%)  2/80 (2.50%) 
Respiratory, thoracic and mediastinal disorders                 
Cough  1  1/78 (1.28%)  2/77 (2.60%)  3/79 (3.80%)  3/79 (3.80%)  0/78 (0.00%)  6/79 (7.59%)  1/79 (1.27%)  3/80 (3.75%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
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: NCT01380730     History of Changes
Other Study ID Numbers: 20101155
First Submitted: June 23, 2011
First Posted: June 27, 2011
Results First Submitted: September 1, 2015
Results First Posted: October 1, 2015
Last Update Posted: November 2, 2018