Goal Achievement After Utilizing an Anti-PCSK9 Antibody i... | NCT01984424

NCT01984424

ID	Type	Description	Link
2013-000935-29	EudraCT Number

Status Module

Oversight Module

Description Module

Detailed Description

The study is divided into 3 parts (A, B, C). After an initial 4-week washout period in which any statins, ezetimibe, or other lipid-lowering agents were discontinued, participants were enrolled in phase A, a double-blind, placebo-controlled crossover procedure to rechallenge patients with atorvastatin. Patients were randomly assigned in a 1:1 ratio to receive either atorvastatin (20 mg daily) or matching placebo for the first 10 weeks (period 1), then underwent a 2-week washout period, followed by crossover to the alternate therapy for a second 10-week period (period 2). Patients who experienced intolerable muscle symptoms during the first period did not complete the full 10 weeks of exposure but entered a 2-week washout period before proceeding to period 2.

Participants who did not develop muscle-related side effects were removed from the study, as were patients who reported muscle-related side effects during a placebo period.

After completion of phase A, patients who experienced muscle-related adverse effects while taking atorvastatin but not placebo were eligible for phase B, a 24-week, double-blind randomization to ezetimibe or evolocumab using a double-dummy design in which patients received either injectable placebo and oral ezetimibe or injectable evolocumab and oral placebo. A patient could proceed directly to phase B if they had a documented history of creatine kinase (CK) elevation more than 10 times the upper limit of normal accompanied by muscle symptoms while taking statin therapy, with documented resolution of both CK elevation and symptoms upon discontinuation of statin therapy.

These study procedures were designed to ensure that only patients with reproducible statin-associated muscle symptoms entered phase B of the study. For phase B, participants were randomized 2:1 to receive subcutaneously administered evolocumab (420 mg monthly) or oral ezetimibe (10 mg daily). Randomization in part B was stratified by screening LDL-C level (< 180 mg/dL [4.66 mmol/L] vs. ≥ 180 mg/dL) at study baseline.

Participants who completed phase B and did not discontinue SC investigational product for any reason, including an adverse event, were eligible to proceed to the 2-year open-label extension phase C to evaluate the long-term safety and efficacy of evolocumab in statin-intolerant patients. Participants in phase C were allowed to choose quarterly between evolocumab 420 mg SC QM or evolocumab 140 mg SC every 2 weeks (Q2W).

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Part A: Atorvastatin 20 mg => Placebo	Other	Participants received atorvastatin 20 mg orally for 10 weeks (period 1) followed by placebo orally for 10 weeks (period 2), separated by a 2-week washout period.	Drug: Atorvastatin Drug: Placebo to Atorvastatin
Part A: Placebo => Atorvastatin 20 mg	Other	Participants received placebo orally for 10 weeks (period 1) followed by atorvastatin 20 mg orally for 10 weeks (period 2), separated by a 2-week washout period.	Drug: Atorvastatin Drug: Placebo to Atorvastatin
Part B: Ezetimibe	Active Comparator	Participants received 10 mg ezetimibe orally only a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.	Drug: Ezetimibe Other: Placebo to Evolocumab
Part B: Evolocumab	Experimental	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.	Other: Placebo to Ezetimibe Drug: Evolocumab
Part C: Open-label Evolocumab	Experimental	Participants who completed part B and were eligible to proceed to open-label extension part C and could choose quarterly between evolocumab 420 mg once a month or evolocumab 140 mg every 2 weeks for up to 2 years.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Atorvastatin	Drug	Atorvastatin was supplied as over-encapsulated 20 mg tablets	Part A: Atorvastatin 20 mg => Placebo Part A: Placebo => Atorvastatin 20 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percent Change From Baseline in LDL-C at the Mean of Weeks 22 and 24		Baseline and weeks 22 and 24
Percent Change From Baseline in LDL-C at Week 24		Baseline and week 24

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in LDL-C at the Mean of Weeks 22 and 24		Baselie and weeks 22 and 24
Change From Baseline in LDL-C at Week 24		Baseline and week 24
Percentage of Participants Who Achieved a Mean LDL-C at Weeks 22 and 24 of Less Than 70 mg/dL

Eligibility Module

Name	Affiliation	Role
MD	Amgen	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Beverly Hills	California	90211	United States
Research Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
30073585	Background	Cho L, Dent R, Stroes ESG, Stein EA, Sullivan D, Ruzza A, Flower A, Somaratne R, Rosenson RS. Persistent Safety and Efficacy of Evolocumab in Patients with Statin Intolerance: a Subset Analysis of the OSLER Open-Label Extension Studies. Cardiovasc Drugs Ther. 2018 Aug;32(4):365-372. doi: 10.1007/s10557-018-6817-7.
33078867	Derived

Label	URL
AmgenTrials clinical trials website	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Ezetimibe	Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
FG001	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00058.5± 9.4 BG00159.0± 11.1 BG00258.8± 10.5

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
< 65 years	BG00052 BG00192 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00039 BG00167 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0012 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Stratification Factor: Screening Low-density Lipoprotein Cholesterol (LDL-C)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
< 180 mg/dL	BG00021 BG00140 BG002

LDL-C Concentation

Mean

Standard Deviation

mg/dL

Title

Denominators

Categories

Title	Measurements
	BG000221.9± 70.2 BG001218.8± 73.1 BG002

Total Cholesterol Concentration

Mean

Standard Deviation

mg/dL

Title

Denominators

Categories

Title	Measurements
	BG000308.0± 73.8 BG001306.5± 75.4 BG002

High-density Lipoprotein Cholesterol (HDL-C)

Mean

Standard Deviation

mg/dL

Title

Denominators

Categories

Title	Measurements
	BG00050.2± 15.5 BG00149.7± 15.4 BG002

Very Low-density Lipoprotein Cholesterol (VLDL-C) Concentration

Mean

Standard Deviation

mg/dL

Title

Denominators

Categories

Title	Measurements
	BG00035.7± 14.3 BG00137.1± 15.6 BG002

Non-high-density Lipoprotein Cholesterol (non-HDL-C) Concentration

Mean

Standard Deviation

mg/dL

Title

Denominators

Categories

Title	Measurements
	BG000257.8± 76.3 BG001256.9± 73.8 BG002

Apolipoprotein B Concentration

Mean

Standard Deviation

mg/dL

Title

Denominators

Categories

Title	Measurements
	BG000155.0± 42.4 BG001158.3± 41.5 BG002

Total Cholesterol/HDL-C Ratio

Mean

Standard Deviation

ratio

Title

Denominators

Categories

Title	Measurements
	BG0006.709± 2.746 BG0016.668± 2.349 BG002

Apolipoprotein B/Apolipoprotein A1 Ratio

Mean

Standard Deviation

ratio

Title

Denominators

Categories

Title	Measurements
	BG0001.063± 0.416 BG0011.063± 0.340 BG002

Triglyceride Concentration

Median

Inter-Quartile Range

mg/dL

Title

Denominators

Categories

Title	Measurements
	BG000162.5(127.0 to 231.0) BG001176.0(128.0 to 233.5) BG002

Lipoprotein(a) Concentration

Median

Inter-Quartile Range

nmol/L

Title

Denominators

Categories

Title	Measurements
	BG00038.0(18.0 to 164.0) BG00129.0(12.5 to 152.5) BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percent Change From Baseline in LDL-C at the Mean of Weeks 22 and 24

Participants randomized and dosed in part B of the study

Posted

Least Squares Mean

Standard Error

percent change

Baseline and weeks 22 and 24

ID	Title	Description
OG000	Ezetimibe	Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
OG001	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.

Units	Counts
Participants	OG00073 OG001145

Title

Denominators

Categories

Title	Measurements
	OG000-16.70± 1.91 OG001-54.50± 1.39

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The null hypothesis was that there was no mean difference in the percent change from baseline at week 24 of part B or in the mean percent change from baseline at weeks 22 and 24 of part B in LDL-C between evolocumab 420 mg and ezetimibe, and the alternative hypothesis was that a mean difference did exist.	Repeated Measures Model	Model includes treatment group, stratification factor (screening LDL-C), scheduled visit and interaction of treatment with scheduled visit.	<0.0001		LS Mean Treatment Difference	-37.79	Standard Error of the Mean	2.29	2-Sided	95	-42.31	-33.28

Primary

Percent Change From Baseline in LDL-C at Week 24

Participants randomized and dosed in part B of the study

Posted

Least Squares Mean

Standard Error

percent change

Baseline and week 24

ID	Title	Description
OG000	Ezetimibe	Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
OG001	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in LDL-C at the Mean of Weeks 22 and 24

Participants randomized and dosed in Part B of the study

Posted

Least Squares Mean

Standard Error

mg/dL

Baselie and weeks 22 and 24

ID	Title	Description
OG000	Ezetimibe	Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
OG001	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in LDL-C at Week 24

Participants randomized and dosed in Part B of the study

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline and week 24

ID	Title	Description
OG000	Ezetimibe	Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
OG001	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants Who Achieved a Mean LDL-C at Weeks 22 and 24 of Less Than 70 mg/dL

Participants randomized and dosed in Part B of the study

Posted

Number

95% Confidence Interval

percentage of participants

Weeks 22 and 24

ID	Title	Description
OG000	Ezetimibe	Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
OG001	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants Who Achieved LDL-C at Week 24 of Less Than 70 mg/dL

Participants randomized and dosed in Part B of the study

Posted

Number

95% Confidence Interval

percentage of participants

Week 24

ID	Title	Description
OG000	Ezetimibe	Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
OG001	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 22 and 24

Participants randomized and dosed in Part B of the study

Posted

Least Squares Mean

Standard Error

percent change

Baseline and weeks 22 and 24

ID	Title	Description
OG000	Ezetimibe	Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
OG001	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Total Cholesterol at Week 24

Participants randomized and dosed in Part B of the study

Posted

Least Squares Mean

Standard Error

percent change

Baseline and week 24

ID	Title	Description
OG000	Ezetimibe	Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
OG001	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 22 and 24

Participants randomized and dosed in Part B of the study

Posted

Least Squares Mean

Standard Error

percent change

Baseline and weeks 22 and 24

ID	Title	Description
OG000	Ezetimibe	Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
OG001	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Non-HDL-C at Week 24

Participants randomized and dosed in Part B of the study

Posted

Least Squares Mean

Standard Error

percent change

Baseline and week 24

ID	Title	Description
OG000	Ezetimibe	Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
OG001	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 22 and 24

Participants randomized and dosed in Part B of the study

Posted

Least Squares Mean

Standard Error

percent change

Baseline and weeks 22 and 24

ID	Title	Description
OG000	Ezetimibe	Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
OG001	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Apolipoprotein B at Week 24

Participants randomized and dosed in Part B of the study

Posted

Least Squares Mean

Standard Error

percent change

Baseline and week 24

ID	Title	Description
OG000	Ezetimibe	Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
OG001	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at the Mean of Weeks 22 and 24

Participants randomized and dosed in Part B of the study

Posted

Least Squares Mean

Standard Error

percent change

Baseline and weeks 22 and 24

ID	Title	Description
OG000	Ezetimibe	Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
OG001	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 24

Participants randomized and dosed in Part B of the study

Posted

Least Squares Mean

Standard Error

percent change

Baseline and week 24

ID	Title	Description
OG000	Ezetimibe	Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
OG001	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 22 and 24

Participants randomized and dosed in Part B of the study.

Posted

Least Squares Mean

Standard Error

percent change

Baseline and Weeks 22 and 24

ID	Title	Description
OG000	Ezetimibe	Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
OG001	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 24

Participants randomized and dosed in Part B of the study

Posted

Least Squares Mean

Standard Error

percent change

Baseline and week 24

ID	Title	Description
OG000	Ezetimibe	Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
OG001	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 22 and 24

Participants randomized and dosed in Part B of the study

Posted

Least Squares Mean

Standard Error

percent change

Baseline and Weeks 22 and 24

ID	Title	Description
OG000	Ezetimibe	Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
OG001	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Lipoprotein(a) at Week 24

Participants randomized and dosed in Part B of the study

Posted

Least Squares Mean

Standard Error

percent change

Baseline and week 24

ID	Title	Description
OG000	Ezetimibe	Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
OG001	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Triglycerides at the Mean of Weeks 22 and 24

Participants randomized and dosed in Part B of the study

Posted

Least Squares Mean

Standard Error

percent change

Baseline and weeks 22 and 24

ID	Title	Description
OG000	Ezetimibe	Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
OG001	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Triglycerides at Week 24

Participants randomized and dosed in Part B of the study

Posted

Least Squares Mean

Standard Error

percent change

Baseline and week 24

ID	Title	Description
OG000	Ezetimibe	Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
OG001	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 24

Participants randomized and dosed in Part B of the study

Posted

Least Squares Mean

Standard Error

percent change

Baseline and weeks 22 and 24

ID	Title	Description
OG000	Ezetimibe	Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
OG001	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in HDL-C at Week 24

Participants randomized and dosed in Part B of the study

Posted

Least Squares Mean

Standard Error

percent change

Baseline and week 24

ID	Title	Description
OG000	Ezetimibe	Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
OG001	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 22 and 24

Participants randomized and dosed in Part B of the study

Posted

Least Squares Mean

Standard Error

percent change

Baseline and weeks 22 and 24

ID	Title	Description
OG000	Ezetimibe	Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
OG001	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in VLDL-C at Week 24

Participants randomized and dosed in Part B of the study

Posted

Least Squares Mean

Standard Error

percent change

Baseline and week 24

ID	Title	Description
OG000	Ezetimibe	Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
OG001	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.			9	145	80	145
EG001	Ezetimibe	Participants received 10 mg ezetimibe orally only a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.			10	73	40	73

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected73 at risk
Angina pectoris	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected145 at risk EG0012 affected73 at risk
Angina unstable	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected73 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected145 at risk EG0010 affected73 at risk
Coronary artery perforation	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected73 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected73 at risk
Hyperparathyroidism	Endocrine disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected73 at risk
Gastrointestinal angiodysplasia	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected73 at risk
Meningitis viral	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected73 at risk
Urinary tract infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected73 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected73 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected73 at risk
Cervical spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected73 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected73 at risk
Adenocarcinoma of colon	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected73 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected73 at risk
Migraine with aura	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected73 at risk
Neuralgia	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected73 at risk
Metrorrhagia	Reproductive system and breast disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected73 at risk
Hypertensive crisis	Vascular disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected73 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0003 affected145 at risk EG0014 affected73 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0006 affected145 at risk EG0014 affected73 at risk
Fatigue	General disorders	MedDRA 18.1	Systematic Assessment	EG00012 affected145 at risk EG0015 affected73 at risk
Influenza like illness	General disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected145 at risk EG0014 affected73 at risk
Bronchitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 affected145 at risk EG0014 affected73 at risk
Nasopharyngitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG00014 affected145 at risk EG0012 affected73 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG00013 affected145 at risk EG0011 affected73 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG00010 affected145 at risk EG0015 affected73 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG00013 affected145 at risk EG0015 affected73 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG00020 affected145 at risk EG00116 affected73 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG00013 affected145 at risk EG0011 affected73 at risk
Headache	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG00010 affected145 at risk EG0017 affected73 at risk

ID	Term
D006949	Hyperlipidemias
D006937	Hypercholesterolemia

ID	Term
D050171	Dyslipidemias
D052439	Lipid Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases

ID	Term
D011758	Pyrroles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D006538	Heptanoic Acids
D005227	Fatty Acids
D008055	Lipids
D001384	Azetidines
D001385	Azetines

ID	Title	Description
BG000	Ezetimibe	Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
BG001	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
BG002	Total	Total of all reporting groups