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

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

Participant Flow

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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
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

Baseline Characteristics

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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
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
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)

Outcome Measures

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1. Primary Outcome

Title	Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
Description	LDL-C was measured using ultracentrifugation.
Time Frame	Baseline and Week 12

Outcome Measure Data

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
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)

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

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

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

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

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

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
Description	LDL-C was measured using ultracentrifugation.
Time Frame	Baseline and Week 12

Outcome Measure Data

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
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)

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

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

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

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

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

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
Description	[Not Specified]
Time Frame	Baseline and Week 12

Outcome Measure Data

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
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)

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

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

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

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

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

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
Description	[Not Specified]
Time Frame	Baseline and Week 12

Outcome Measure Data

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
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)

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

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

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

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

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

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
Description	[Not Specified]
Time Frame	Baseline and Week 12

Outcome Measure Data

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
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)

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

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

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

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

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

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
Description	[Not Specified]
Time Frame	Baseline and Week 12

Outcome Measure Data

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
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)

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

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

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

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

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

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

Adverse Events

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Top of Page Participant Flow Baseline Characteristics Outcome Measures Adverse Events Limitations and Caveats Information More Information

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
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	--/--	--/--	--/--	--/--	--/--	--/--	--/--	--/--
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
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

Limitations and Caveats

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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

Publications:

Giugliano RP, Desai NR, Kohli P, Rogers WJ, Somaratne R, Huang F, Liu T, Mohanavelu S, Hoffman EB, McDonald ST, Abrahamsen TE, Wasserman SM, Scott R, Sabatine MS; LAPLACE-TIMI 57 Investigators. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 study. Lancet. 2012 Dec 8;380(9858):2007-17. doi: 10.1016/S0140-6736(12)61770-X. Epub 2012 Nov 6.

Kohli P, Desai NR, Giugliano RP, Kim JB, Somaratne R, Huang F, Knusel B, McDonald S, Abrahamsen T, Wasserman SM, Scott R, Sabatine MS. Design and rationale of the LAPLACE-TIMI 57 trial: a phase II, double-blind, placebo-controlled study of the efficacy and tolerability of a monoclonal antibody inhibitor of PCSK9 in subjects with hypercholesterolemia on background statin therapy. Clin Cardiol. 2012;35(7):385-91. doi: 10.1002/clc.22014. Epub 2012 Jun 19.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Desai NR, Kohli P, Giugliano RP, O'Donoghue ML, Somaratne R, Zhou J, Hoffman EB, Huang F, Rogers WJ, Wasserman SM, Scott R, Sabatine MS. AMG145, a monoclonal antibody against proprotein convertase subtilisin kexin type 9, significantly reduces lipoprotein(a) in hypercholesterolemic patients receiving statin therapy: an analysis from the LDL-C Assessment with Proprotein Convertase Subtilisin Kexin Type 9 Monoclonal Antibody Inhibition Combined with Statin Therapy (LAPLACE)-Thrombolysis in Myocardial Infarction (TIMI) 57 trial. Circulation. 2013 Aug 27;128(9):962-9. doi: 10.1161/CIRCULATIONAHA.113.001969. Epub 2013 Jul 24.

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