Trial Outcomes & Findings for Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-3 (NCT NCT01984424)

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

511 participants

Primary outcome timeframe

Baseline and weeks 22 and 24

Results posted on

2018-11-29

Participant Flow

A total of 511 participants were enrolled (492 in Part A and 19 directly in Part B) at 53 centers in the United States of America, Europe, Australia, New Zealand, Canada, and South Africa from December 2013 to November 2014. Results are reported for participants randomized in Part B. Part C was ongoing at the time of this analysis.

A total of 492 patients were randomized in part A; of those, 202 completed both periods and experienced muscle-related side effects during the atorvastatin period and not during the placebo period. Of the 202, 199 enrolled in Part B. Nineteen additional patients bypassed part A, as permitted by protocol, and advanced directly into part B.

Participant milestones

Participant milestones
Measure	Ezetimibe Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Evolocumab Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
Overall Study STARTED	73	145
Overall Study COMPLETED	70	138
Overall Study NOT COMPLETED	3	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Ezetimibe Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Evolocumab Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
Overall Study Withdrawal by Subject	3	5
Overall Study Sponsor Decision	0	1
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-3

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ezetimibe n=73 Participants Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Evolocumab n=145 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.	Total n=218 Participants Total of all reporting groups
Age, Continuous	58.5 years STANDARD_DEVIATION 9.4 • n=5 Participants	59.0 years STANDARD_DEVIATION 11.1 • n=7 Participants	58.8 years STANDARD_DEVIATION 10.5 • n=5 Participants
Age, Customized < 65 years	52 Participants n=5 Participants	92 Participants n=7 Participants	144 Participants n=5 Participants
Age, Customized ≥ 65 years	21 Participants n=5 Participants	53 Participants n=7 Participants	74 Participants n=5 Participants
Sex: Female, Male Female	39 Participants n=5 Participants	67 Participants n=7 Participants	106 Participants n=5 Participants
Sex: Female, Male Male	34 Participants n=5 Participants	78 Participants n=7 Participants	112 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	73 Participants n=5 Participants	143 Participants n=7 Participants	216 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	69 Participants n=5 Participants	138 Participants n=7 Participants	207 Participants n=5 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Stratification Factor: Screening Low-density Lipoprotein Cholesterol (LDL-C) < 180 mg/dL	21 Participants n=5 Participants	40 Participants n=7 Participants	61 Participants n=5 Participants
Stratification Factor: Screening Low-density Lipoprotein Cholesterol (LDL-C) ≥ 180 mg/dL	52 Participants n=5 Participants	105 Participants n=7 Participants	157 Participants n=5 Participants
LDL-C Concentation	221.9 mg/dL STANDARD_DEVIATION 70.2 • n=5 Participants	218.8 mg/dL STANDARD_DEVIATION 73.1 • n=7 Participants	219.9 mg/dL STANDARD_DEVIATION 72.0 • n=5 Participants
Total Cholesterol Concentration	308.0 mg/dL STANDARD_DEVIATION 73.8 • n=5 Participants	306.5 mg/dL STANDARD_DEVIATION 75.4 • n=7 Participants	307.0 mg/dL STANDARD_DEVIATION 74.7 • n=5 Participants
High-density Lipoprotein Cholesterol (HDL-C)	50.2 mg/dL STANDARD_DEVIATION 15.5 • n=5 Participants	49.7 mg/dL STANDARD_DEVIATION 15.4 • n=7 Participants	49.8 mg/dL STANDARD_DEVIATION 15.4 • n=5 Participants
Very Low-density Lipoprotein Cholesterol (VLDL-C) Concentration	35.7 mg/dL STANDARD_DEVIATION 14.3 • n=5 Participants	37.1 mg/dL STANDARD_DEVIATION 15.6 • n=7 Participants	36.7 mg/dL STANDARD_DEVIATION 15.1 • n=5 Participants
Non-high-density Lipoprotein Cholesterol (non-HDL-C) Concentration	257.8 mg/dL STANDARD_DEVIATION 76.3 • n=5 Participants	256.9 mg/dL STANDARD_DEVIATION 73.8 • n=7 Participants	257.2 mg/dL STANDARD_DEVIATION 74.5 • n=5 Participants
Apolipoprotein B Concentration	155.0 mg/dL STANDARD_DEVIATION 42.4 • n=5 Participants	158.3 mg/dL STANDARD_DEVIATION 41.5 • n=7 Participants	157.2 mg/dL STANDARD_DEVIATION 41.7 • n=5 Participants
Total Cholesterol/HDL-C Ratio	6.709 ratio STANDARD_DEVIATION 2.746 • n=5 Participants	6.668 ratio STANDARD_DEVIATION 2.349 • n=7 Participants	6.682 ratio STANDARD_DEVIATION 2.483 • n=5 Participants
Apolipoprotein B/Apolipoprotein A1 Ratio	1.063 ratio STANDARD_DEVIATION 0.416 • n=5 Participants	1.063 ratio STANDARD_DEVIATION 0.340 • n=7 Participants	1.063 ratio STANDARD_DEVIATION 0.366 • n=5 Participants
Triglyceride Concentration	162.5 mg/dL n=5 Participants	176.0 mg/dL n=7 Participants	171.3 mg/dL n=5 Participants
Lipoprotein(a) Concentration	38.0 nmol/L n=5 Participants	29.0 nmol/L n=7 Participants	31.0 nmol/L n=5 Participants

PRIMARY outcome

Timeframe: Baseline and weeks 22 and 24

Population: Participants randomized and dosed in part B of the study

Outcome measures

Outcome measures
Measure	Ezetimibe n=73 Participants Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Evolocumab n=145 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
Percent Change From Baseline in LDL-C at the Mean of Weeks 22 and 24	-16.70 percent change Standard Error 1.91	-54.50 percent change Standard Error 1.39

PRIMARY outcome

Timeframe: Baseline and week 24

Population: Participants randomized and dosed in part B of the study

Outcome measures

Outcome measures
Measure	Ezetimibe n=73 Participants Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Evolocumab n=145 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
Percent Change From Baseline in LDL-C at Week 24	-16.69 percent change Standard Error 2.11	-52.76 percent change Standard Error 1.52

SECONDARY outcome

Timeframe: Baselie and weeks 22 and 24

Population: Participants randomized and dosed in Part B of the study

Outcome measures

Outcome measures
Measure	Ezetimibe n=73 Participants Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Evolocumab n=145 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
Change From Baseline in LDL-C at the Mean of Weeks 22 and 24	-31.0 mg/dL Standard Error 3.8	-106.8 mg/dL Standard Error 2.7

SECONDARY outcome

Timeframe: Baseline and week 24

Population: Participants randomized and dosed in Part B of the study

Outcome measures

Outcome measures
Measure	Ezetimibe n=73 Participants Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Evolocumab n=145 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
Change From Baseline in LDL-C at Week 24	-31.2 mg/dL Standard Error 4.0	-102.9 mg/dL Standard Error 2.9

SECONDARY outcome

Timeframe: Weeks 22 and 24

Population: Participants randomized and dosed in Part B of the study

Outcome measures

Outcome measures
Measure	Ezetimibe n=73 Participants Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Evolocumab n=145 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
Percentage of Participants Who Achieved a Mean LDL-C at Weeks 22 and 24 of Less Than 70 mg/dL	1.4 percentage of participants Interval 0.3 to 7.7	29.9 percentage of participants Interval 22.9 to 38.1

SECONDARY outcome

Timeframe: Week 24

Population: Participants randomized and dosed in Part B of the study

Outcome measures

Outcome measures
Measure	Ezetimibe n=73 Participants Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Evolocumab n=145 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
Percentage of Participants Who Achieved LDL-C at Week 24 of Less Than 70 mg/dL	0.0 percentage of participants Interval 0.0 to 6.3	27.4 percentage of participants Interval 20.1 to 36.1

SECONDARY outcome

Timeframe: Baseline and weeks 22 and 24

Population: Participants randomized and dosed in Part B of the study

Outcome measures

Outcome measures
Measure	Ezetimibe n=73 Participants Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Evolocumab n=145 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 22 and 24	-11.43 percent change Standard Error 1.41	-38.04 percent change Standard Error 1.03

SECONDARY outcome

Timeframe: Baseline and week 24

Population: Participants randomized and dosed in Part B of the study

Outcome measures

Outcome measures
Measure	Ezetimibe n=73 Participants Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Evolocumab n=145 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
Percent Change From Baseline in Total Cholesterol at Week 24	-11.57 percent change Standard Error 1.52	-36.64 percent change Standard Error 1.10

SECONDARY outcome

Timeframe: Baseline and weeks 22 and 24

Population: Participants randomized and dosed in Part B of the study

Outcome measures

Outcome measures
Measure	Ezetimibe n=73 Participants Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Evolocumab n=145 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 22 and 24	-14.38 percent change Standard Error 1.72	-47.44 percent change Standard Error 1.25

SECONDARY outcome

Timeframe: Baseline and week 24

Population: Participants randomized and dosed in Part B of the study

Outcome measures

Outcome measures
Measure	Ezetimibe n=73 Participants Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Evolocumab n=145 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
Percent Change From Baseline in Non-HDL-C at Week 24	-14.62 percent change Standard Error 1.83	-45.72 percent change Standard Error 1.32

SECONDARY outcome

Timeframe: Baseline and weeks 22 and 24

Population: Participants randomized and dosed in Part B of the study

Outcome measures

Outcome measures
Measure	Ezetimibe n=73 Participants Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Evolocumab n=145 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 22 and 24	-11.42 percent change Standard Error 1.82	-45.28 percent change Standard Error 1.31

SECONDARY outcome

Timeframe: Baseline and week 24

Population: Participants randomized and dosed in Part B of the study

Outcome measures

Outcome measures
Measure	Ezetimibe n=73 Participants Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Evolocumab n=145 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
Percent Change From Baseline in Apolipoprotein B at Week 24	-11.74 percent change Standard Error 1.94	-43.50 percent change Standard Error 1.40

SECONDARY outcome

Timeframe: Baseline and weeks 22 and 24

Population: Participants randomized and dosed in Part B of the study

Outcome measures

Outcome measures
Measure	Ezetimibe n=73 Participants Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Evolocumab n=145 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at the Mean of Weeks 22 and 24	-11.48 percent change Standard Error 1.75	-41.39 percent change Standard Error 1.27

SECONDARY outcome

Timeframe: Baseline and week 24

Population: Participants randomized and dosed in Part B of the study

Outcome measures

Outcome measures
Measure	Ezetimibe n=173 Participants Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Evolocumab n=145 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 24	-12.84 percent change Standard Error 1.85	-40.04 percent change Standard Error 1.33

SECONDARY outcome

Timeframe: Baseline and Weeks 22 and 24

Population: Participants randomized and dosed in Part B of the study.

Outcome measures

Outcome measures
Measure	Ezetimibe n=73 Participants Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Evolocumab n=145 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 22 and 24	-11.86 percent change Standard Error 1.89	-45.99 percent change Standard Error 1.36

SECONDARY outcome

Timeframe: Baseline and week 24

Population: Participants randomized and dosed in Part B of the study

Outcome measures

Outcome measures
Measure	Ezetimibe n=73 Participants Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Evolocumab n=145 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 24	-12.62 percent change Standard Error 1.97	-44.60 percent change Standard Error 1.41

SECONDARY outcome

Timeframe: Baseline and Weeks 22 and 24

Population: Participants randomized and dosed in Part B of the study

Outcome measures

Outcome measures
Measure	Ezetimibe n=73 Participants Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Evolocumab n=145 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 22 and 24	-1.63 percent change Standard Error 2.80	-22.71 percent change Standard Error 2.03

SECONDARY outcome

Timeframe: Baseline and week 24

Population: Participants randomized and dosed in Part B of the study

Outcome measures

Outcome measures
Measure	Ezetimibe n=73 Participants Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Evolocumab n=145 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
Percent Change From Baseline in Lipoprotein(a) at Week 24	0.17 percent change Standard Error 3.05	-21.06 percent change Standard Error 2.19

SECONDARY outcome

Timeframe: Baseline and weeks 22 and 24

Population: Participants randomized and dosed in Part B of the study

Outcome measures

Outcome measures
Measure	Ezetimibe n=73 Participants Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Evolocumab n=145 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
Percent Change From Baseline in Triglycerides at the Mean of Weeks 22 and 24	-0.95 percent change Standard Error 3.94	-5.39 percent change Standard Error 2.84

SECONDARY outcome

Timeframe: Baseline and week 24

Population: Participants randomized and dosed in Part B of the study

Outcome measures

Outcome measures
Measure	Ezetimibe n=73 Participants Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Evolocumab n=145 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
Percent Change From Baseline in Triglycerides at Week 24	-1.07 percent change Standard Error 4.97	-2.88 percent change Standard Error 3.54

SECONDARY outcome

Timeframe: Baseline and weeks 22 and 24

Population: Participants randomized and dosed in Part B of the study

Outcome measures

Outcome measures
Measure	Ezetimibe n=73 Participants Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Evolocumab n=145 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 24	1.66 percent change Standard Error 1.71	7.85 percent change Standard Error 1.24

SECONDARY outcome

Timeframe: Baseline and week 24

Population: Participants randomized and dosed in Part B of the study

Outcome measures

Outcome measures
Measure	Ezetimibe n=73 Participants Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Evolocumab n=145 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
Percent Change From Baseline in HDL-C at Week 24	2.90 percent change Standard Error 1.89	7.40 percent change Standard Error 1.36

SECONDARY outcome

Timeframe: Baseline and weeks 22 and 24

Population: Participants randomized and dosed in Part B of the study

Outcome measures

Outcome measures
Measure	Ezetimibe n=73 Participants Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Evolocumab n=145 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 22 and 24	-2.15 percent change Standard Error 3.22	-6.81 percent change Standard Error 2.33

SECONDARY outcome

Timeframe: Baseline and week 24

Population: Participants randomized and dosed in Part B of the study

Outcome measures

Outcome measures
Measure	Ezetimibe n=73 Participants Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Evolocumab n=145 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
Percent Change From Baseline in VLDL-C at Week 24	-2.66 percent change Standard Error 3.88	-3.90 percent change Standard Error 2.78

Adverse Events

Evolocumab

Serious events: 9 serious events

Other events: 80 other events

Deaths: 0 deaths

Ezetimibe

Serious events: 10 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Evolocumab n=145 participants at risk Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.	Ezetimibe n=73 participants at risk Participants received 10 mg ezetimibe orally only a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
Gastrointestinal disorders Constipation	2.1% 3/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.5% 4/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Diarrhoea	4.1% 6/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.5% 4/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Fatigue	8.3% 12/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.8% 5/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Influenza like illness	0.69% 1/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.5% 4/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Bronchitis	0.69% 1/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.5% 4/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Nasopharyngitis	9.7% 14/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.7% 2/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Arthralgia	9.0% 13/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 1/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Back pain	6.9% 10/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.8% 5/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Muscle spasms	9.0% 13/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.8% 5/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Myalgia	13.8% 20/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	21.9% 16/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Pain in extremity	9.0% 13/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 1/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Headache	6.9% 10/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	9.6% 7/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. 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

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

Measure	Evolocumab n=145 participants at risk Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.	Ezetimibe n=73 participants at risk Participants received 10 mg ezetimibe orally only a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
Cardiac disorders Acute myocardial infarction	0.00% 0/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 1/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Angina pectoris	0.69% 1/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.7% 2/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Angina unstable	0.00% 0/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 1/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Atrial fibrillation	1.4% 2/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Coronary artery perforation	0.69% 1/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Myocardial ischaemia	0.69% 1/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Endocrine disorders Hyperparathyroidism	0.69% 1/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Gastrointestinal angiodysplasia	0.00% 0/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 1/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Meningitis viral	0.69% 1/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Urinary tract infection	0.00% 0/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 1/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 1/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 1/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Cervical spinal stenosis	0.69% 1/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.69% 1/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.69% 1/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Carotid artery stenosis	0.00% 0/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 1/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Migraine with aura	0.69% 1/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Neuralgia	0.00% 0/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 1/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Reproductive system and breast disorders Metrorrhagia	0.00% 0/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 1/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypertensive crisis	0.69% 1/145 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/73 • 6 months Results are reported for participants randomized in Part B. Adverse event data are not included for Part A as this phase was designed to ensure that only patients with reproducible statin-associated muscle symptoms entered Part B and was not the focus of the study. Part C was still ongoing at the time of this analysis. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.