Trial Outcomes & Findings for Safety and Efficacy of Evolocumab in Combination With Statin Therapy in Adults With Diabetes and Hyperlipidemia or Mixed Dyslipidemia (NCT NCT02662569)

NCT ID: NCT02662569

Last Updated: 2019-01-11

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

986 participants

Primary outcome timeframe

Baseline and weeks 10 and 12

Results posted on

2019-01-11

Participant Flow

Participants were enrolled at 102 study centers and randomized at 98 centers in Argentina, Brazil, Canada, China, Colombia, France, Republic of Korea, Russian Federation, Turkey, and the United States from 14 April 2016 to 28 July 2017.

Participants who met eligibility criteria and completed at least 4 weeks of lipid stabilization on atorvastatin 20 mg daily were randomized in a 1:1:2:2 ratio to receive placebo every 2 weeks (Q2W), placebo once a month (QM), evolocumab Q2W, or evolocumab QM. Randomization was stratified by entry statin therapy and geographic region.

Participant milestones

Participant milestones
Measure	Placebo Q2W Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Placebo QM Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab Q2W Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab QM Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.
Overall Study STARTED	166	161	327	332
Overall Study Received Study Drug	164	160	325	332
Overall Study COMPLETED	159	160	321	328
Overall Study NOT COMPLETED	7	1	6	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Q2W Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Placebo QM Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab Q2W Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab QM Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.
Overall Study Withdrawal by Subject	6	1	6	4
Overall Study Lost to Follow-up	1	0	0	0

Baseline Characteristics

Full analysis set, defined as all randomized participants who received at least 1 dose of study drug (subcutaneous evolocumab or placebo to evolocumab).

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo Q2W n=166 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Placebo QM n=161 Participants Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab Q2W n=327 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab QM n=332 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.	Total n=986 Participants Total of all reporting groups
Age, Continuous	61.6 years STANDARD_DEVIATION 8.8 • n=166 Participants	61.0 years STANDARD_DEVIATION 8.8 • n=161 Participants	61.0 years STANDARD_DEVIATION 8.5 • n=327 Participants	61.6 years STANDARD_DEVIATION 8.4 • n=332 Participants	61.3 years STANDARD_DEVIATION 8.6 • n=986 Participants
Age, Customized 18 - 64 years	105 Participants n=166 Participants	101 Participants n=161 Participants	206 Participants n=327 Participants	208 Participants n=332 Participants	620 Participants n=986 Participants
Age, Customized 65 - 80 years	61 Participants n=166 Participants	60 Participants n=161 Participants	121 Participants n=327 Participants	124 Participants n=332 Participants	366 Participants n=986 Participants
Sex: Female, Male Female	102 Participants n=166 Participants	94 Participants n=161 Participants	178 Participants n=327 Participants	190 Participants n=332 Participants	564 Participants n=986 Participants
Sex: Female, Male Male	64 Participants n=166 Participants	67 Participants n=161 Participants	149 Participants n=327 Participants	142 Participants n=332 Participants	422 Participants n=986 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	29 Participants n=166 Participants	34 Participants n=161 Participants	65 Participants n=327 Participants	67 Participants n=332 Participants	195 Participants n=986 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	137 Participants n=166 Participants	127 Participants n=161 Participants	262 Participants n=327 Participants	265 Participants n=332 Participants	791 Participants n=986 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=166 Participants	0 Participants n=161 Participants	0 Participants n=327 Participants	0 Participants n=332 Participants	0 Participants n=986 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=166 Participants	1 Participants n=161 Participants	1 Participants n=327 Participants	0 Participants n=332 Participants	2 Participants n=986 Participants
Race/Ethnicity, Customized Asian	82 Participants n=166 Participants	80 Participants n=161 Participants	164 Participants n=327 Participants	166 Participants n=332 Participants	492 Participants n=986 Participants
Race/Ethnicity, Customized Black or African American	7 Participants n=166 Participants	6 Participants n=161 Participants	11 Participants n=327 Participants	18 Participants n=332 Participants	42 Participants n=986 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=166 Participants	0 Participants n=161 Participants	0 Participants n=327 Participants	0 Participants n=332 Participants	0 Participants n=986 Participants
Race/Ethnicity, Customized White	72 Participants n=166 Participants	68 Participants n=161 Participants	140 Participants n=327 Participants	140 Participants n=332 Participants	420 Participants n=986 Participants
Race/Ethnicity, Customized Multiple	5 Participants n=166 Participants	6 Participants n=161 Participants	11 Participants n=327 Participants	8 Participants n=332 Participants	30 Participants n=986 Participants
Stratification Factor: Statin Therapy at Study Entry Intensive statin usage	16 Participants n=166 Participants	15 Participants n=161 Participants	31 Participants n=327 Participants	32 Participants n=332 Participants	94 Participants n=986 Participants
Stratification Factor: Statin Therapy at Study Entry Non-intensive statin usage	83 Participants n=166 Participants	80 Participants n=161 Participants	167 Participants n=327 Participants	166 Participants n=332 Participants	496 Participants n=986 Participants
Stratification Factor: Statin Therapy at Study Entry No statin	67 Participants n=166 Participants	66 Participants n=161 Participants	129 Participants n=327 Participants	134 Participants n=332 Participants	396 Participants n=986 Participants
Stratification Factor: Geographic Region China	76 Participants n=166 Participants	75 Participants n=161 Participants	150 Participants n=327 Participants	152 Participants n=332 Participants	453 Participants n=986 Participants
Stratification Factor: Geographic Region South Korea	6 Participants n=166 Participants	5 Participants n=161 Participants	14 Participants n=327 Participants	13 Participants n=332 Participants	38 Participants n=986 Participants
Stratification Factor: Geographic Region Other countries	84 Participants n=166 Participants	81 Participants n=161 Participants	163 Participants n=327 Participants	167 Participants n=332 Participants	495 Participants n=986 Participants
Low-density Lipoprotein Cholesterol (LDL-C) Concentration	92.2 mg/dL STANDARD_DEVIATION 32.0 • n=164 Participants • Full analysis set, defined as all randomized participants who received at least 1 dose of study drug (subcutaneous evolocumab or placebo to evolocumab).	91.0 mg/dL STANDARD_DEVIATION 30.7 • n=160 Participants • Full analysis set, defined as all randomized participants who received at least 1 dose of study drug (subcutaneous evolocumab or placebo to evolocumab).	92.4 mg/dL STANDARD_DEVIATION 33.8 • n=325 Participants • Full analysis set, defined as all randomized participants who received at least 1 dose of study drug (subcutaneous evolocumab or placebo to evolocumab).	93.5 mg/dL STANDARD_DEVIATION 33.6 • n=332 Participants • Full analysis set, defined as all randomized participants who received at least 1 dose of study drug (subcutaneous evolocumab or placebo to evolocumab).	92.5 mg/dL STANDARD_DEVIATION 32.9 • n=981 Participants • Full analysis set, defined as all randomized participants who received at least 1 dose of study drug (subcutaneous evolocumab or placebo to evolocumab).
Non-high-density Lipoprotein Cholesterol (non-HDL-C) Concentration	119.2 mg/dL STANDARD_DEVIATION 38.2 • n=164 Participants • Full analysis set	119.4 mg/dL STANDARD_DEVIATION 36.0 • n=160 Participants • Full analysis set	121.3 mg/dL STANDARD_DEVIATION 38.1 • n=325 Participants • Full analysis set	121.2 mg/dL STANDARD_DEVIATION 37.0 • n=332 Participants • Full analysis set	120.6 mg/dL STANDARD_DEVIATION 37.4 • n=981 Participants • Full analysis set
Apolipoprotein B100 Concentration	82.1 mg/dL STANDARD_DEVIATION 23.1 • n=162 Participants • Full analysis set with available data	83.4 mg/dL STANDARD_DEVIATION 22.3 • n=158 Participants • Full analysis set with available data	84.8 mg/dL STANDARD_DEVIATION 23.0 • n=325 Participants • Full analysis set with available data	84.4 mg/dL STANDARD_DEVIATION 21.8 • n=332 Participants • Full analysis set with available data	84.0 mg/dL STANDARD_DEVIATION 22.5 • n=977 Participants • Full analysis set with available data
Total Cholesterol	166.5 mg/dL STANDARD_DEVIATION 38.6 • n=164 Participants • Full analysis set	169.3 mg/dL STANDARD_DEVIATION 37.5 • n=160 Participants • Full analysis set	167.8 mg/dL STANDARD_DEVIATION 38.9 • n=325 Participants • Full analysis set	168.9 mg/dL STANDARD_DEVIATION 38.9 • n=332 Participants • Full analysis set	168.2 mg/dL STANDARD_DEVIATION 38.6 • n=981 Participants • Full analysis set
Total Cholesterol/High-density Lipoprotein Cholesterol(HDL-C) Ratio	3.717 ratio STANDARD_DEVIATION 1.337 • n=164 Participants • Full analysis set	3.598 ratio STANDARD_DEVIATION 1.071 • n=160 Participants • Full analysis set	3.804 ratio STANDARD_DEVIATION 1.273 • n=325 Participants • Full analysis set	3.725 ratio STANDARD_DEVIATION 1.201 • n=332 Participants • Full analysis set	3.729 ratio STANDARD_DEVIATION 1.229 • n=981 Participants • Full analysis set
Apolipoprotein B100/Apolipoprotein A1 Ratio	0.573 ratio STANDARD_DEVIATION 0.192 • n=162 Participants • Full analysis set with available data	0.563 ratio STANDARD_DEVIATION 0.161 • n=158 Participants • Full analysis set with available data	0.601 ratio STANDARD_DEVIATION 0.200 • n=325 Participants • Full analysis set with available data	0.586 ratio STANDARD_DEVIATION 0.185 • n=332 Participants • Full analysis set with available data	0.585 ratio STANDARD_DEVIATION 0.188 • n=977 Participants • Full analysis set with available data
Lipoprotein (a)	67.0 nmol/L STANDARD_DEVIATION 90.9 • n=164 Participants • Full analysis set	71.8 nmol/L STANDARD_DEVIATION 96.5 • n=160 Participants • Full analysis set	65.6 nmol/L STANDARD_DEVIATION 92.5 • n=325 Participants • Full analysis set	73.2 nmol/L STANDARD_DEVIATION 95.9 • n=332 Participants • Full analysis set	69.4 nmol/L STANDARD_DEVIATION 94.0 • n=981 Participants • Full analysis set
Triglycerides Concentration	137.3 mg/dL STANDARD_DEVIATION 77.3 • n=164 Participants • Full analysis set	150.6 mg/dL STANDARD_DEVIATION 154.6 • n=160 Participants • Full analysis set	145.9 mg/dL STANDARD_DEVIATION 67.5 • n=325 Participants • Full analysis set	139.7 mg/dL STANDARD_DEVIATION 64.9 • n=332 Participants • Full analysis set	143.1 mg/dL STANDARD_DEVIATION 88.4 • n=981 Participants • Full analysis set
High-density Lipoprotein Cholesterol (HDL-C) Concentration	47.3 mg/dL STANDARD_DEVIATION 11.9 • n=164 Participants • Full analysis set	49.9 mg/dL STANDARD_DEVIATION 15.2 • n=160 Participants • Full analysis set	46.5 mg/dL STANDARD_DEVIATION 11.5 • n=325 Participants • Full analysis set	47.6 mg/dL STANDARD_DEVIATION 12.3 • n=332 Participants • Full analysis set	47.6 mg/dL STANDARD_DEVIATION 12.6 • n=981 Participants • Full analysis set
Very Low-density Lipoprotein Cholesterol (VLDL-C) Concentration	27.3 mg/dL STANDARD_DEVIATION 14.9 • n=164 Participants • Full analysis set	28.4 mg/dL STANDARD_DEVIATION 16.2 • n=160 Participants • Full analysis set	28.7 mg/dL STANDARD_DEVIATION 12.6 • n=325 Participants • Full analysis set	27.8 mg/dL STANDARD_DEVIATION 12.7 • n=332 Participants • Full analysis set	28.1 mg/dL STANDARD_DEVIATION 13.7 • n=981 Participants • Full analysis set

PRIMARY outcome

Timeframe: Baseline and weeks 10 and 12

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Placebo Q2W n=164 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Placebo QM n=160 Participants Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab Q2W n=325 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab QM n=332 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.
Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12	4.94 percent change Standard Error 3.48	0.99 percent change Standard Error 3.31	-65.35 percent change Standard Error 3.09	-69.05 percent change Standard Error 2.96

PRIMARY outcome

Timeframe: Baseline and week 12

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Placebo Q2W n=164 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Placebo QM n=160 Participants Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab Q2W n=325 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab QM n=332 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.
Percent Change From Baseline in LDL-C at Week 12	7.10 percent change Standard Error 3.66	2.63 percent change Standard Error 3.41	-64.66 percent change Standard Error 3.20	-62.30 percent change Standard Error 3.02

SECONDARY outcome

Timeframe: Baseline and weeks 10 and 12

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Placebo Q2W n=164 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Placebo QM n=160 Participants Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab Q2W n=325 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab QM n=332 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.
Change From Baseline in LDL-C at the Mean of Weeks 10 and 12	-2.1 mg/dL Standard Error 4.1	-8.8 mg/dL Standard Error 4.0	-64.6 mg/dL Standard Error 3.6	-71.9 mg/dL Standard Error 3.6

SECONDARY outcome

Timeframe: Baseline and week 12

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Placebo Q2W n=164 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Placebo QM n=160 Participants Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab Q2W n=325 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab QM n=332 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.
Change From Baseline in LDL-C at Week 12	-0.3 mg/dL Standard Error 4.2	-7.3 mg/dL Standard Error 4.1	-63.9 mg/dL Standard Error 3.7	-66.1 mg/dL Standard Error 3.7

SECONDARY outcome

Timeframe: Baseline and weeks 10 and 12

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Placebo Q2W n=164 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Placebo QM n=160 Participants Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab Q2W n=325 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab QM n=332 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.
Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12	4.33 percent change Standard Error 3.05	0.33 percent change Standard Error 2.95	-56.57 percent change Standard Error 2.70	-59.08 percent change Standard Error 2.63

SECONDARY outcome

Timeframe: Baseline and week 12

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Placebo Q2W n=164 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Placebo QM n=160 Participants Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab Q2W n=325 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab QM n=332 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.
Percent Change From Baseline in Non-HDL-C at Week 12	5.87 percent change Standard Error 3.20	1.30 percent change Standard Error 3.03	-55.76 percent change Standard Error 2.79	-52.92 percent change Standard Error 2.69

SECONDARY outcome

Timeframe: Baseline and weeks 10 and 12

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Placebo Q2W n=164 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Placebo QM n=160 Participants Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab Q2W n=325 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab QM n=332 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.
Percent Change From Baseline in Apolipoprotein B100 at the Mean of Weeks 10 and 12	1.97 percent change Standard Error 3.31	-1.52 percent change Standard Error 2.99	-54.96 percent change Standard Error 3.07	-56.37 percent change Standard Error 2.72

SECONDARY outcome

Timeframe: Baseline and week 12

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Placebo Q2W n=164 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Placebo QM n=160 Participants Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab Q2W n=325 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab QM n=332 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.
Percent Change From Baseline in Apolipoprotein B100 at Week 12	3.17 percent change Standard Error 3.42	-0.26 percent change Standard Error 3.03	-53.90 percent change Standard Error 3.14	-49.68 percent change Standard Error 2.75

SECONDARY outcome

Timeframe: Baseline and weeks 10 and 12

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Placebo Q2W n=164 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Placebo QM n=160 Participants Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab Q2W n=325 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab QM n=332 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.
Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12	2.89 percent change Standard Error 2.30	-0.25 percent change Standard Error 2.18	-38.64 percent change Standard Error 2.04	-39.74 percent change Standard Error 1.95

SECONDARY outcome

Timeframe: Baseline and week 12

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Placebo Q2W n=164 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Placebo QM n=160 Participants Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab Q2W n=325 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab QM n=332 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.
Percent Change From Baseline in Total Cholesterol at Week 12	4.40 percent change Standard Error 2.40	0.67 percent change Standard Error 2.24	-37.82 percent change Standard Error 2.10	-35.22 percent change Standard Error 1.99

SECONDARY outcome

Timeframe: Baseline and weeks 10 and 12

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Placebo Q2W n=164 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Placebo QM n=160 Participants Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab Q2W n=325 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab QM n=332 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.
Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12	3.03 percent change Standard Error 2.38	-2.03 percent change Standard Error 2.41	-41.06 percent change Standard Error 2.11	-45.70 percent change Standard Error 2.17

SECONDARY outcome

Timeframe: Baseline and week 12

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Placebo Q2W n=164 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Placebo QM n=160 Participants Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab Q2W n=325 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab QM n=332 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.
Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12	3.22 percent change Standard Error 2.49	-1.22 percent change Standard Error 2.47	-40.72 percent change Standard Error 2.18	-41.78 percent change Standard Error 2.21

SECONDARY outcome

Timeframe: Baseline and weeks 10 and 12

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Placebo Q2W n=164 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Placebo QM n=160 Participants Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab Q2W n=325 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab QM n=332 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.
Percent Change From Baseline in Apolipoprotein B100/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12	2.60 percent change Standard Error 3.30	-1.02 percent change Standard Error 3.09	-55.60 percent change Standard Error 3.07	-57.75 percent change Standard Error 2.82

SECONDARY outcome

Timeframe: Baseline and week 12

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Placebo Q2W n=164 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Placebo QM n=160 Participants Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab Q2W n=325 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab QM n=332 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.
Percent Change From Baseline in Apolipoprotein B100/Apolipoprotein A1 Ratio at Week 12	3.23 percent change Standard Error 3.39	-0.10 percent change Standard Error 3.16	-54.98 percent change Standard Error 3.12	-51.80 percent change Standard Error 2.86

SECONDARY outcome

Timeframe: Weeks 10 and 12

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Placebo Q2W n=164 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Placebo QM n=160 Participants Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab Q2W n=325 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab QM n=332 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.
Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L)	21.7 percentage of participants Interval 15.9 to 28.7	19.4 percentage of participants Interval 13.9 to 26.3	90.1 percentage of participants Interval 86.2 to 92.9	91.3 percentage of participants Interval 87.6 to 93.9

SECONDARY outcome

Timeframe: Week 12

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Placebo Q2W n=164 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Placebo QM n=160 Participants Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab Q2W n=325 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab QM n=332 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.
Percentage of Participants With LDL-C Less Than 70 mg/dL (1.8 mmol/L) at Week 12	20.9 percentage of participants Interval 15.2 to 28.2	21.3 percentage of participants Interval 15.5 to 28.6	88.2 percentage of participants Interval 84.0 to 91.4	90.2 percentage of participants Interval 86.2 to 93.1

SECONDARY outcome

Timeframe: Baseline and weeks 10 and 12

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Placebo Q2W n=164 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Placebo QM n=160 Participants Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab Q2W n=325 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab QM n=332 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.
Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12	16.89 percent change Standard Error 17.49	8.48 percent change Standard Error 9.49	-38.63 percent change Standard Error 13.67	-42.29 percent change Standard Error 8.49

SECONDARY outcome

Timeframe: Baseline and week 12

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Placebo Q2W n=164 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Placebo QM n=160 Participants Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab Q2W n=325 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab QM n=332 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.
Percent Change From Baseline in Lipoprotein(a) at Week 12	26.53 percent change Standard Error 21.78	7.47 percent change Standard Error 10.40	-35.93 percent change Standard Error 16.47	-37.85 percent change Standard Error 9.02

SECONDARY outcome

Timeframe: Baseline and weeks 10 and 12

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Placebo Q2W n=164 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Placebo QM n=160 Participants Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab Q2W n=325 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab QM n=332 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.
Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12	11.54 percent change Standard Error 5.27	8.48 percent change Standard Error 4.48	-6.48 percent change Standard Error 4.70	-7.15 percent change Standard Error 4.02

SECONDARY outcome

Timeframe: Baseline and week 12

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Placebo Q2W n=164 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Placebo QM n=160 Participants Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab Q2W n=325 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab QM n=332 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.
Percent Change From Baseline in Triglycerides at Week 12	10.50 percent change Standard Error 5.36	8.07 percent change Standard Error 4.57	-5.91 percent change Standard Error 4.75	-4.24 percent change Standard Error 4.09

SECONDARY outcome

Timeframe: Baseline and weeks 10 and 12

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Placebo Q2W n=164 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Placebo QM n=160 Participants Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab Q2W n=325 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab QM n=332 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.
Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12	1.25 percent change Standard Error 2.19	5.88 percent change Standard Error 2.11	7.59 percent change Standard Error 1.99	13.75 percent change Standard Error 1.90

SECONDARY outcome

Timeframe: Baseline and week 12

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Placebo Q2W n=164 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Placebo QM n=160 Participants Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab Q2W n=325 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab QM n=332 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.
Percent Change From Baseline in HDL-C at Week 12	2.57 percent change Standard Error 2.29	6.04 percent change Standard Error 2.18	8.45 percent change Standard Error 2.04	14.18 percent change Standard Error 1.95

SECONDARY outcome

Timeframe: Baseline and weeks 10 and 12

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Placebo Q2W n=164 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Placebo QM n=160 Participants Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab Q2W n=325 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab QM n=332 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.
Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12	9.63 percent change Standard Error 4.70	7.92 percent change Standard Error 4.43	-17.55 percent change Standard Error 4.19	-16.09 percent change Standard Error 3.99

Adverse Events

Placebo Q2W

Serious events: 6 serious events

Other events: 28 other events

Deaths: 0 deaths

Placebo QM

Serious events: 5 serious events

Other events: 22 other events

Deaths: 0 deaths

Evolocumab Q2W

Serious events: 10 serious events

Other events: 45 other events

Deaths: 0 deaths

Evolocumab QM

Serious events: 22 serious events

Other events: 49 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo Q2W n=164 participants at risk Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Placebo QM n=160 participants at risk Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab Q2W n=325 participants at risk Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Evolocumab QM n=332 participants at risk Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.
Infections and infestations Nasopharyngitis	3.7% 6/164 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.8% 6/160 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.8% 9/325 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.3% 11/332 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Upper respiratory tract infection	3.7% 6/164 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.1% 5/160 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.8% 9/325 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.9% 13/332 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Diabetes mellitus	1.2% 2/164 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.5% 4/160 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.6% 15/325 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.5% 15/332 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypoglycaemia	3.0% 5/164 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/160 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.62% 2/325 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.60% 2/332 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Arthralgia	0.61% 1/164 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.5% 4/160 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.92% 3/325 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.90% 3/332 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Cough	2.4% 4/164 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.2% 2/160 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.31% 1/325 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 6/332 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypertension	3.7% 6/164 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.9% 3/160 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.5% 8/325 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.5% 5/332 • From the first dose of study drug to 30 days after last dose; up to 14 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER