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Clinical Trial Results:
A Double-blind, Randomized, Placebo and Ezetimibe Controlled, Multicenter Study to Evaluate Safety, Tolerability and Efficacy of AMG 145 on LDL-C in Combination With Statin Therapy in Subjects With Primary Hypercholesterolemia and Mixed Dyslipidemia

Summary
EudraCT number	2012-001363-70
Trial protocol	BE ES HU NL IT CZ SE DK GB DE
Global end of trial date	04 Dec 2013

Results information
Results version number	v1(current)
This version publication date	20 Jun 2016
First version publication date	06 Aug 2015
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

20110115

ISRCTN number

US NCT number

NCT01763866

WHO universal trial number (UTN)

Sponsor organisation name

Amgen, Inc.

Sponsor organisation address

One Amgen Center Drive, Thousand Oaks, CA, United States, 91320

Public contact

IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com

Scientific contact

IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

04 Dec 2013

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

04 Dec 2013

Was the trial ended prematurely?

Main objective of the trial

The primary objective was to evaluate the effect of 12 weeks of evolocumab administered subcutaneously every 2 weeks (Q2W) and monthly (QM) when used in combination with a statin, compared with placebo, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in patients with primary hypercholesterolemia and mixed dyslipidemia.

Protection of trial subjects

This study was conducted in accordance with International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) regulations and guidelines, and Food and Drug Administration (FDA) regulations, and guidelines set forth in 21 CFR Parts 11, 50, 54, 56, and 312. All subjects provided written informed consent before undergoing any study-related procedures, including screening procedures. The study protocol, amendments, and the informed consent form (ICF) were reviewed by the Institutional Review Boards (IRBs) and Independent Ethics Committees (IECs). No subjects were recruited into the study and no investigational product (IP) was shipped until the IRB/IEC gave written approval of the protocol and ICF and Amgen received copies of these approvals.

Background therapy

Evidence for comparator

Actual start date of recruitment

15 Jan 2013

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 558

Country: Number of subjects enrolled

Belgium: 38

Country: Number of subjects enrolled

Canada: 176

Country: Number of subjects enrolled

Czech Republic: 238

Country: Number of subjects enrolled

Denmark: 137

Country: Number of subjects enrolled

France: 16

Country: Number of subjects enrolled

Germany: 123

Country: Number of subjects enrolled

Hungary: 64

Country: Number of subjects enrolled

Italy: 53

Country: Number of subjects enrolled

Netherlands: 40

Country: Number of subjects enrolled

Russian Federation: 122

Country: Number of subjects enrolled

Spain: 21

Country: Number of subjects enrolled

Sweden: 35

Country: Number of subjects enrolled

Switzerland: 24

Country: Number of subjects enrolled

United Kingdom: 200

Country: Number of subjects enrolled

Australia: 47

Country: Number of subjects enrolled

Hong Kong: 7

Worldwide total number of subjects

1899

EEA total number of subjects

965

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

1226

From 65 to 84 years

673

85 years and over

Subject disposition

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Recruitment details

Patients aged 18 to 80 years with a screening LDL-C level of ≥ 150 mg/dL (no statin at screening), ≥ 100 mg/dL (nonintensive statin at screening), or ≥ 80 mg/dL (intensive statin at screening) and fasting triglyceride levels of 400 mg/dL or less. First patient enrolled on 15 January2013; Last patient enrolled on 10 July 2013.

Screening details

A total of 2067 patients were first randomized to 1 of the 5 open-label statin cohorts (atorvastatin 10 mg or 80 mg, rosuvastatin 5 mg or 40 mg, or simvastatin 40 mg), and 1899 were randomized to investigational product. Randomization into the statin dose cohorts was stratified by entry statin therapy and by use of certain concomitant medications.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

A10 PBO Q2W

Arm description

Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo to Evolocumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Investigational medicinal product name

Placebo to Ezetimibe

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once daily

Investigational medicinal product name

Atorvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

A10 PBO QM

Arm description

Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo to Evolocumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Investigational medicinal product name

Placebo to Ezetimibe

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once daily

Investigational medicinal product name

Atorvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

A10 EZE (Q2W)

Arm description

Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once a day for up to 12 weeks.

Arm type

Active comparator

Investigational medicinal product name

Placebo to Evolocumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Investigational medicinal product name

Ezetimibe

Investigational medicinal product code

Zetia

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once daily

Investigational medicinal product name

Atorvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

A10 EZE (QM)

Arm description

Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.

Arm type

Active comparator

Investigational medicinal product name

Placebo to Evolocumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Investigational medicinal product name

Ezetimibe

Investigational medicinal product code

Zetia

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once daily

Investigational medicinal product name

Atorvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

A10 EvoMab Q2W

Arm description

Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.

Arm type

Experimental

Investigational medicinal product name

Evolocumab

Investigational medicinal product code

AMG 145

Other name

Repatha

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Investigational medicinal product name

Placebo to Ezetimibe

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once daily

Investigational medicinal product name

Atorvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

A10 EvoMab QM

Arm description

Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.

Arm type

Experimental

Investigational medicinal product name

Evolocumab

Investigational medicinal product code

AMG 145

Other name

Repatha

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Investigational medicinal product name

Placebo to Ezetimibe

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once daily

Investigational medicinal product name

Atorvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

A80 PBO Q2W

Arm description

Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo to Evolocumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Investigational medicinal product name

Placebo to Ezetimibe

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once daily

Investigational medicinal product name

Atorvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

A80 PBO QM

Arm description

Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month and placebo tablets once a day for up to 12 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo to Evolocumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Investigational medicinal product name

Placebo to Ezetimibe

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once daily

Investigational medicinal product name

Atorvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

A80 EZE (Q2W)

Arm description

Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.

Arm type

Active comparator

Investigational medicinal product name

Placebo to Evolocumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Investigational medicinal product name

Ezetimibe

Investigational medicinal product code

Zetia

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once daily

Investigational medicinal product name

Atorvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

A80 EZE (QM)

Arm description

Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.

Arm type

Active comparator

Investigational medicinal product name

Placebo to Evolocumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Investigational medicinal product name

Ezetimibe

Investigational medicinal product code

Zetia

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once daily

Investigational medicinal product name

Atorvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

A80 EvoMab Q2W

Arm description

Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.

Arm type

Experimental

Investigational medicinal product name

Evolocumab

Investigational medicinal product code

AMG 145

Other name

Repatha

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Investigational medicinal product name

Placebo to Ezetimibe

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once daily

Investigational medicinal product name

Atorvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

A80 EvoMab QM

Arm description

Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.

Arm type

Experimental

Investigational medicinal product name

Evolocumab

Investigational medicinal product code

AMG 145

Other name

Repatha

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Investigational medicinal product name

Placebo to Ezetimibe

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once daily

Investigational medicinal product name

Atorvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

R5 PBO Q2W

Arm description

Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo to Evolocumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Investigational medicinal product name

Rosuvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

R5 PBO QM

Arm description

Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month for up to 12 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo to Evolocumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Investigational medicinal product name

Rosuvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

R5 EvoMab Q2W

Arm description

Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.

Arm type

Experimental

Investigational medicinal product name

Evolocumab

Investigational medicinal product code

AMG 145

Other name

Repatha

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Investigational medicinal product name

Rosuvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

R5 EvoMab QM

Arm description

Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.

Arm type

Experimental

Investigational medicinal product name

Evolocumab

Investigational medicinal product code

AMG 145

Other name

Repatha

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Investigational medicinal product name

Rosuvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

R40 PBO Q2W

Arm description

Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo to Evolocumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Investigational medicinal product name

Rosuvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

R40 PBO QM

Arm description

Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month for up to 12 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo to Evolocumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Investigational medicinal product name

Rosuvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

R40 EvoMab Q2W

Arm description

Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.

Arm type

Experimental

Investigational medicinal product name

Evolocumab

Investigational medicinal product code

AMG 145

Other name

Repatha

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Investigational medicinal product name

Rosuvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

R40 EvoMab QM

Arm description

Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.

Arm type

Experimental

Investigational medicinal product name

Evolocumab

Investigational medicinal product code

AMG 145

Other name

Repatha

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Investigational medicinal product name

Rosuvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

S40 PBO Q2W

Arm description

Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo to Evolocumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Investigational medicinal product name

Simvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

S40 PBO QM

Arm description

Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month for up to 12 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo to Evolocumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Investigational medicinal product name

Simvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

S40 EvoMab Q2W

Arm description

Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.

Arm type

Experimental

Investigational medicinal product name

Evolocumab

Investigational medicinal product code

AMG 145

Other name

Repatha

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Investigational medicinal product name

Simvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

S40 EvoMab QM

Arm description

Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.

Arm type

Experimental

Investigational medicinal product name

Evolocumab

Investigational medicinal product code

AMG 145

Other name

Repatha

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Investigational medicinal product name

Simvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once a day

Number of subjects in period 1	A10 PBO Q2W	A10 PBO QM	A10 EZE (Q2W)	A10 EZE (QM)	A10 EvoMab Q2W	A10 EvoMab QM	A80 PBO Q2W	A80 PBO QM	A80 EZE (Q2W)	A80 EZE (QM)	A80 EvoMab Q2W	A80 EvoMab QM	R5 PBO Q2W	R5 PBO QM	R5 EvoMab Q2W	R5 EvoMab QM	R40 PBO Q2W	R40 PBO QM	R40 EvoMab Q2W	R40 EvoMab QM	S40 PBO Q2W	S40 PBO QM	S40 EvoMab Q2W	S40 EvoMab QM
Started	56	55	56	55	110	110	55	55	56	54	110	110	58	57	114	115	56	56	111	112	56	55	112	115
Received Treatment	56	55	56	55	110	110	55	55	56	54	109	110	58	57	113	115	56	55	111	112	56	55	112	115
Completed	54	54	51	55	108	107	48	55	53	53	102	108	54	57	102	112	55	55	105	110	52	54	109	113
Not completed	2	1	5	0	2	3	7	0	3	1	8	2	4	0	12	3	1	1	6	2	4	1	3	2
Consent withdrawn by subject	2	1	4	-	-	3	4	-	1	1	2	2	2	-	6	3	-	1	1	1	2	1	2	1
Death	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	1	-	-	-	-	-	-	-
Lost to follow-up	-	-	-	-	-	-	1	-	-	-	-	-	1	-	1	-	-	-	1	1	-	-	-	1
Decision by sponsor	-	-	1	-	2	-	2	-	2	-	6	-	1	-	5	-	-	-	4	-	2	-	1	-

Baseline characteristics

Top of page

Reporting group title

A10 PBO Q2W

Reporting group description

Reporting group title

A10 PBO QM

Reporting group description

Reporting group title

A10 EZE (Q2W)

Reporting group description

Reporting group title

A10 EZE (QM)

Reporting group description

Reporting group title

A10 EvoMab Q2W

Reporting group description

Reporting group title

A10 EvoMab QM

Reporting group description

Reporting group title

A80 PBO Q2W

Reporting group description

Reporting group title

A80 PBO QM

Reporting group description

Reporting group title

A80 EZE (Q2W)

Reporting group description

Reporting group title

A80 EZE (QM)

Reporting group description

Reporting group title

A80 EvoMab Q2W

Reporting group description

Reporting group title

A80 EvoMab QM

Reporting group description

Reporting group title

R5 PBO Q2W

Reporting group description

Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks.

Reporting group title

R5 PBO QM

Reporting group description

Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month for up to 12 weeks.

Reporting group title

R5 EvoMab Q2W

Reporting group description

Reporting group title

R5 EvoMab QM

Reporting group description

Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.

Reporting group title

R40 PBO Q2W

Reporting group description

Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks.

Reporting group title

R40 PBO QM

Reporting group description

Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month for up to 12 weeks.

Reporting group title

R40 EvoMab Q2W

Reporting group description

Reporting group title

R40 EvoMab QM

Reporting group description

Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.

Reporting group title

S40 PBO Q2W

Reporting group description

Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks.

Reporting group title

S40 PBO QM

Reporting group description

Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month for up to 12 weeks.

Reporting group title

S40 EvoMab Q2W

Reporting group description

Reporting group title

S40 EvoMab QM

Reporting group description

Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.

Reporting group values	A10 PBO Q2W	A10 PBO QM	A10 EZE (Q2W)	A10 EZE (QM)	A10 EvoMab Q2W	A10 EvoMab QM	A80 PBO Q2W	A80 PBO QM	A80 EZE (Q2W)	A80 EZE (QM)	A80 EvoMab Q2W	A80 EvoMab QM	R5 PBO Q2W	R5 PBO QM	R5 EvoMab Q2W	R5 EvoMab QM	R40 PBO Q2W	R40 PBO QM	R40 EvoMab Q2W	R40 EvoMab QM	S40 PBO Q2W	S40 PBO QM	S40 EvoMab Q2W	S40 EvoMab QM	Total
Number of subjects	56	55	56	55	110	110	55	55	56	54	110	110	58	57	114	115	56	56	111	112	56	55	112	115	1899
Age categorical
Units: Subjects
Age Continuous
Units: years
arithmetic mean (standard deviation)	58.3 ( 10.5 )	62.2 ( 10.4 )	61 ( 9 )	60.6 ( 9.2 )	58.3 ( 8.4 )	59.6 ( 11.1 )	57.1 ( 9.9 )	58.8 ( 11.5 )	60.5 ( 10.2 )	61.1 ( 8.9 )	59.7 ( 10.2 )	60.1 ( 10.2 )	61.2 ( 9.1 )	59.6 ( 9.2 )	58.9 ( 11.2 )	59.3 ( 10.5 )	60.2 ( 8.7 )	58.3 ( 11.3 )	59.5 ( 9.2 )	59.6 ( 9 )	61.9 ( 9.7 )	61.5 ( 10.3 )	59.7 ( 9.2 )	61.5 ( 9.6 )	-
Gender, Male/Female
Units: participants
Female	24	28	29	28	56	44	22	24	24	28	44	48	35	27	52	51	21	27	43	52	32	28	45	59	871
Male	32	27	27	27	54	66	33	31	32	26	66	62	23	30	62	64	35	29	68	60	24	27	67	56	1028
Race/Ethnicity, Customized
Units: Subjects
Hispanic or Latino	3	2	2	1	5	2	5	5	4	4	5	7	2	4	6	3	2	3	6	5	1	2	3	5	87
Not Hispanic or Latino	53	53	54	54	105	108	50	50	52	50	105	103	56	53	108	112	54	53	105	107	55	53	109	110	1812
Race/Ethnicity, Customized
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1
Asian	1	0	2	1	3	4	1	0	0	3	1	1	0	0	2	1	1	0	0	0	3	0	1	0	25
Black or African American	3	0	1	2	9	4	1	2	3	4	3	4	2	1	7	5	0	3	5	3	3	1	4	5	75
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	1	0	0	0	0	1	0	0	0	4
White	52	55	53	52	97	101	51	52	53	46	105	105	56	56	104	107	55	52	105	109	49	54	106	110	1785
Other	0	0	0	0	1	0	2	0	0	0	1	0	0	0	1	1	0	1	0	0	0	0	0	0	7
Mixed Race	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	2
Stratification Factor: Entry Statin Therapy
Intensive statin use was defined as daily atorvastatin (40mg or greater), rosuvastatin (20mg or greater), simvastatin (80 mg), or any statin plus ezetimibe.
Units: Subjects
Intensive statin use	18	19	10	14	28	35	15	12	21	11	34	35	13	13	33	38	13	13	33	37	19	13	31	34	542
Non-intensive statin use	20	25	30	21	52	40	22	27	22	21	47	46	25	28	49	42	23	22	50	44	21	26	45	48	796
No statin use	18	11	16	20	30	35	18	16	13	22	29	29	20	16	32	35	20	21	28	31	16	16	36	33	561
Low-Density Lipoprotein Cholesterol (LDL-C) Concentration
Data are provided for the full analysis set (all participants randomized to investigational product (IP) who received at least 1 dose of IP (subcutaneously or orally).
Units: mg/dL
arithmetic mean (standard deviation)	123 ( 46.6 )	123.7 ( 47.9 )	126.8 ( 49.6 )	119.3 ( 28.1 )	124.2 ( 43.4 )	126.1 ( 50.4 )	100.3 ( 36.2 )	94.7 ( 31.9 )	98.7 ( 34 )	92.3 ( 19.3 )	94.2 ( 34.8 )	93.8 ( 32.3 )	115.6 ( 39.8 )	119.9 ( 39.1 )	118.7 ( 40.9 )	122.9 ( 42 )	77.4 ( 20.9 )	102.9 ( 49.3 )	88.5 ( 31.5 )	88.5 ( 31.3 )	110.3 ( 28 )	108.6 ( 30.9 )	114.9 ( 34.5 )	123.7 ( 48.5 )	-
Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Concentration
Data are provided for the full analysis set.
Units: mg/dL
arithmetic mean (standard deviation)	149.1 ( 46.9 )	147.7 ( 51.4 )	153.8 ( 53.2 )	148.3 ( 36.8 )	152.3 ( 45.6 )	154.3 ( 53.1 )	124.2 ( 39.3 )	116.5 ( 35.7 )	124.8 ( 35.4 )	118.4 ( 25.5 )	120.2 ( 42.3 )	117.2 ( 36.3 )	141.1 ( 41.6 )	148.3 ( 43.3 )	146.6 ( 43.2 )	152 ( 46.4 )	103.9 ( 25.7 )	128.7 ( 53.4 )	113.5 ( 36 )	114.3 ( 34.7 )	138.4 ( 29.3 )	135.7 ( 38.4 )	146.8 ( 41.8 )	151.2 ( 51.5 )	-
Apolipoprotein B Concentration
Data are provided for the full analysis set
Units: mg/dL
arithmetic mean (standard deviation)	95.3 ( 26 )	95.3 ( 29.6 )	101.3 ( 31.2 )	94.6 ( 20.4 )	99.7 ( 26.4 )	97.3 ( 28.9 )	81.1 ( 22.1 )	80.1 ( 21.4 )	85.3 ( 23.1 )	78.7 ( 16.9 )	79.9 ( 25.1 )	77.9 ( 21.5 )	93.1 ( 27.3 )	95.9 ( 25.2 )	95.4 ( 27 )	97.2 ( 26.9 )	71 ( 16.6 )	84.8 ( 29.7 )	77.4 ( 22.3 )	78.7 ( 23.1 )	91.6 ( 18.4 )	89.8 ( 20.7 )	94.2 ( 24 )	96.5 ( 27.5 )	-
Total Cholesterol/HDL-C Ratio
Data are provided for the full analysis set
Units: ratio
arithmetic mean (standard deviation)	3.988 ( 1.154 )	3.859 ( 1.396 )	4.112 ( 1.311 )	4.002 ( 1.1 )	3.98 ( 1.224 )	4.1 ( 1.636 )	3.704 ( 1.26 )	3.461 ( 1.093 )	3.748 ( 1.099 )	3.54 ( 1.1 )	3.696 ( 1.371 )	3.462 ( 1 )	4.044 ( 1.685 )	3.891 ( 1.234 )	3.915 ( 1.216 )	4.178 ( 1.932 )	3.086 ( 0.728 )	3.547 ( 1.355 )	3.413 ( 1.355 )	3.307 ( 1.061 )	3.733 ( 1.079 )	3.595 ( 1.345 )	4.196 ( 1.436 )	3.924 ( 1.42 )	-
Apolipoprotein B/Apolipoprotein A1 Ratio
Data are provided for the full analysis set
Units: ratio
arithmetic mean (standard deviation)	0.666 ( 0.216 )	0.647 ( 0.266 )	0.692 ( 0.243 )	0.64 ( 0.169 )	0.663 ( 0.217 )	0.659 ( 0.249 )	0.603 ( 0.221 )	0.571 ( 0.189 )	0.64 ( 0.234 )	0.56 ( 0.157 )	0.593 ( 0.227 )	0.562 ( 0.171 )	0.661 ( 0.273 )	0.636 ( 0.207 )	0.64 ( 0.249 )	0.676 ( 0.341 )	0.479 ( 0.129 )	0.562 ( 0.217 )	0.538 ( 0.227 )	0.536 ( 0.193 )	0.611 ( 0.179 )	0.581 ( 0.174 )	0.657 ( 0.193 )	0.639 ( 0.224 )	-
Lipoprotein(a) Concentration
Data are provided for the full analysis set
Units: nmol/L
median (inter-quartile range (Q1-Q3))	31.5 (13 to 87.5)	41 (15 to 106)	37 (9.5 to 190)	33 (8 to 163)	27 (8 to 120)	49 (11 to 169)	53 (15 to 177)	50 (13 to 152)	25 (12 to 108)	61.5 (12 to 192)	32 (11.5 to 135.5)	24.5 (8 to 93)	34 (8 to 158)	35 (14 to 156.5)	38 (11 to 165)	32 (9 to 172)	28.5 (7 to 171)	33 (11 to 148)	41 (10 to 183)	49.5 (11 to 184.5)	36.5 (17.5 to 140.5)	28 (13 to 180)	32.5 (13 to 157)	37 (11 to 141)	-
Triglyceride Concentration
Data are provided for the full analysis set
Units: mg/dL
median (inter-quartile range (Q1-Q3))	112 (83 to 176)	108 (83 to 145)	129.5 (94 to 151.5)	119 (87 to 168)	135 (99 to 189)	119 (84 to 161)	104 (82 to 142)	104 (76 to 124)	133 (89 to 155)	109 (80 to 171)	104 (81 to 163)	106.5 (79 to 137)	112.5 (89 to 148)	134 (86 to 184)	116 (90 to 168)	121 (93 to 161)	128 (91.5 to 162)	116 (78 to 160)	102 (79 to 151)	119.5 (87 to 149.5)	124 (90 to 173)	106 (87 to 139)	129 (91.5 to 195)	110 (84 to 161)	-
Very Low Density Lipoprotein Cholesterol (VLDL-C) Concentration
Data are provided for the full analysis set
Units: mg/dL
median (inter-quartile range (Q1-Q3))	22 (17 to 35)	22 (17 to 29)	25.5 (19 to 30)	24 (17 to 33)	27 (20 to 38)	24 (17 to 32)	21 (16 to 28)	21 (15 to 25)	26.5 (18 to 31)	22 (16 to 34)	21 (16 to 33)	21 (16 to 27)	22.5 (18 to 30)	27 (17 to 37)	23 (18 to 34)	24 (19 to 32)	26 (18.5 to 32.5)	23 (16 to 32)	20 (16 to 30)	24 (17 to 30)	25 (18 to 34.5)	21 (17 to 26)	26 (18.5 to 39)	22 (17 to 32)	-
HDL-C Concentration
Data are provided for the full anlaysis set
Units: mg/dL
arithmetic mean (standard deviation)	54.1 ( 16.6 )	57.9 ( 18.4 )	54.1 ( 17.2 )	52.7 ( 13.7 )	56 ( 17.9 )	56.1 ( 17.8 )	50.6 ( 15.6 )	50.9 ( 13 )	48.7 ( 12.6 )	51.6 ( 15.1 )	48.5 ( 12.9 )	50.8 ( 13.5 )	52.1 ( 14.9 )	55.5 ( 16 )	54.5 ( 15 )	54 ( 16 )	52.8 ( 12.9 )	56 ( 18.7 )	53.2 ( 16.4 )	53.8 ( 14.6 )	55 ( 14.2 )	59.9 ( 21.8 )	49.7 ( 12.6 )	57.3 ( 17.4 )	-

End points

Top of page

Reporting group title

A10 PBO Q2W

Reporting group description

Reporting group title

A10 PBO QM

Reporting group description

Reporting group title

A10 EZE (Q2W)

Reporting group description

Reporting group title

A10 EZE (QM)

Reporting group description

Reporting group title

A10 EvoMab Q2W

Reporting group description

Reporting group title

A10 EvoMab QM

Reporting group description

Reporting group title

A80 PBO Q2W

Reporting group description

Reporting group title

A80 PBO QM

Reporting group description

Reporting group title

A80 EZE (Q2W)

Reporting group description

Reporting group title

A80 EZE (QM)

Reporting group description

Reporting group title

A80 EvoMab Q2W

Reporting group description

Reporting group title

A80 EvoMab QM

Reporting group description

Reporting group title

R5 PBO Q2W

Reporting group description

Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks.

Reporting group title

R5 PBO QM

Reporting group description

Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month for up to 12 weeks.

Reporting group title

R5 EvoMab Q2W

Reporting group description

Reporting group title

R5 EvoMab QM

Reporting group description

Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.

Reporting group title

R40 PBO Q2W

Reporting group description

Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks.

Reporting group title

R40 PBO QM

Reporting group description

Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month for up to 12 weeks.

Reporting group title

R40 EvoMab Q2W

Reporting group description

Reporting group title

R40 EvoMab QM

Reporting group description

Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.

Reporting group title

S40 PBO Q2W

Reporting group description

Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks.

Reporting group title

S40 PBO QM

Reporting group description

Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month for up to 12 weeks.

Reporting group title

S40 EvoMab Q2W

Reporting group description

Reporting group title

S40 EvoMab QM

Reporting group description

Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.

Primary: Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12

Top of page

End point title

Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12

End point description

Calculated LDL-C was determined based on the Friedewald equation. Efficacy analyses were performed on the full analysis set. Least squares (LS) means are from a repeated measures linear effects model; missing values were not imputed.

End point type

Primary

End point timeframe

Baseline and Week 12

End point values	A10 PBO Q2W	A10 PBO QM	A10 EZE (Q2W)	A10 EZE (QM)	A10 EvoMab Q2W	A10 EvoMab QM	A80 PBO Q2W	A80 PBO QM	A80 EZE (Q2W)	A80 EZE (QM)	A80 EvoMab Q2W	A80 EvoMab QM	R5 PBO Q2W	R5 PBO QM	R5 EvoMab Q2W	R5 EvoMab QM	R40 PBO Q2W	R40 PBO QM	R40 EvoMab Q2W	R40 EvoMab QM	S40 PBO Q2W	S40 PBO QM	S40 EvoMab Q2W	S40 EvoMab QM
Number of subjects analysed	56	55	56	55	110	110	55	55	56	54	109	110	58	57	113	115	56	55	111	112	56	55	112	115
Units: percent change
least squares mean (standard error)	9.86 ( 2.53 )	0.97 ( 2.82 )	-21.96 ( 2.63 )	-17.08 ( 2.78 )	-61.56 ( 1.81 )	-58.19 ( 1.99 )	14.49 ( 4.42 )	11.83 ( 3.85 )	-14.6 ( 4.29 )	-19.8 ( 3.85 )	-61.8 ( 3.04 )	-58.68 ( 2.74 )	8.12 ( 2.68 )	5.1 ( 2.62 )	-60.09 ( 1.94 )	-59.4 ( 1.87 )	9.42 ( 3.6 )	2.59 ( 4.3 )	-58.89 ( 2.58 )	-52.4 ( 2.98 )	4.7 ( 3.61 )	3.4 ( 4.94 )	-65.86 ( 3.05 )	-57.02 ( 3.93 )

A10: Evolocumab Q2W vs Placebo Q2W

Statistical analysis description

The null hypothesis was that there was no difference in the percent change from Baseline at Week 12 in LDL-C between evolocumab and placebo, and the alternative hypothesis was that a mean difference did exist.

Comparison groups

A10 EvoMab Q2W v A10 PBO Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[1]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-71.42

Confidence interval

level

95%

sides

2-sided

lower limit

-77.55

upper limit

-65.29

Variability estimate

Standard error of the mean

Dispersion value

3.11

Notes
[1] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Placebo QM

Statistical analysis description

Comparison groups

A10 PBO QM v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[2]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-59.16

Confidence interval

level

95%

sides

2-sided

lower limit

-65.94

upper limit

-52.38

Variability estimate

Standard error of the mean

Dispersion value

3.44

Notes
[2] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab Q2W vs Ezetimibe (Q2W)

Statistical analysis description

The null hypothesis was that there was no mean difference in the percent change from Baseline at Week 12 in LDL-C between evolocumab and ezetimibe, and the alternative hypothesis was that a mean difference did exist.

Comparison groups

A10 EZE (Q2W) v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[3]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-39.6

Confidence interval

level

95%

sides

2-sided

lower limit

-45.81

upper limit

-33.4

Variability estimate

Standard error of the mean

Dispersion value

3.15

Notes
[3] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Ezetimibe (QM)

Statistical analysis description

Comparison groups

A10 EZE (QM) v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[4]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-41.1

Confidence interval

level

95%

sides

2-sided

lower limit

-47.83

upper limit

-34.37

Variability estimate

Standard error of the mean

Dispersion value

3.41

Notes
[4] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Placebo Q2W

Statistical analysis description

Comparison groups

A80 PBO Q2W v A80 EvoMab Q2W

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[5]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-76.29

Confidence interval

level

95%

sides

2-sided

lower limit

-86.87

upper limit

-65.72

Variability estimate

Standard error of the mean

Dispersion value

5.36

Notes
[5] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Placebo QM

Statistical analysis description

Comparison groups

A80 PBO QM v A80 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[6]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-70.51

Confidence interval

level

95%

sides

2-sided

lower limit

-79.81

upper limit

-61.2

Variability estimate

Standard error of the mean

Dispersion value

4.72

Notes
[6] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Ezetimibe (Q2W)

Statistical analysis description

Comparison groups

A80 EZE (Q2W) v A80 EvoMab Q2W

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[7]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-47.2

Confidence interval

level

95%

sides

2-sided

lower limit

-57.54

upper limit

-36.86

Variability estimate

Standard error of the mean

Dispersion value

5.24

Notes
[7] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Ezetimibe (QM)

Statistical analysis description

Comparison groups

A80 EZE (QM) v A80 EvoMab QM

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[8]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-38.88

Confidence interval

level

95%

sides

2-sided

lower limit

-48.21

upper limit

-29.56

Variability estimate

Standard error of the mean

Dispersion value

4.73

Notes
[8] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab Q2W vs Placebo Q2W

Statistical analysis description

Comparison groups

R5 PBO Q2W v R5 EvoMab Q2W

Number of subjects included in analysis

171

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[9]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-68.21

Confidence interval

level

95%

sides

2-sided

lower limit

-74.72

upper limit

-61.7

Variability estimate

Standard error of the mean

Dispersion value

3.3

Notes
[9] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab QM vs Placebo QM

Statistical analysis description

Comparison groups

R5 PBO QM v R5 EvoMab QM

Number of subjects included in analysis

172

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[10]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-64.49

Confidence interval

level

95%

sides

2-sided

lower limit

-70.84

upper limit

-58.14

Variability estimate

Standard error of the mean

Dispersion value

3.21

Notes
[10] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab Q2W vs Placebo Q2W

Statistical analysis description

Comparison groups

R40 PBO Q2W v R40 EvoMab Q2W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[11]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-68.31

Confidence interval

level

95%

sides

2-sided

lower limit

-77.04

upper limit

-59.57

Variability estimate

Standard error of the mean

Dispersion value

4.42

Notes
[11] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab QM vs Placebo QM

Statistical analysis description

Comparison groups

R40 PBO QM v R40 EvoMab QM

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[12]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-54.98

Confidence interval

level

95%

sides

2-sided

lower limit

-65.31

upper limit

-44.65

Variability estimate

Standard error of the mean

Dispersion value

5.23

Notes
[12] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab Q2W vs Placebo Q2W

Statistical analysis description

Comparison groups

S40 PBO Q2W v S40 EvoMab Q2W

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[13]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-70.56

Confidence interval

level

95%

sides

2-sided

lower limit

-76.72

upper limit

-64.41

Variability estimate

Standard error of the mean

Dispersion value

3.12

Notes
[13] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab QM vs Placebo QM

Statistical analysis description

Comparison groups

S40 PBO QM v S40 EvoMab QM

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[14]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-60.41

Confidence interval

level

95%

sides

2-sided

lower limit

-69.11

upper limit

-51.72

Variability estimate

Standard error of the mean

Dispersion value

4.41

Notes
[14] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

Primary: Mean Percent Change From Baseline in LDL-C at Weeks 10 and 12

Top of page

End point title

Mean Percent Change From Baseline in LDL-C at Weeks 10 and 12

End point description

End point type

Primary

End point timeframe

Baseline and Weeks 10 and 12

End point values	A10 PBO Q2W	A10 PBO QM	A10 EZE (Q2W)	A10 EZE (QM)	A10 EvoMab Q2W	A10 EvoMab QM	A80 PBO Q2W	A80 PBO QM	A80 EZE (Q2W)	A80 EZE (QM)	A80 EvoMab Q2W	A80 EvoMab QM	R5 PBO Q2W	R5 PBO QM	R5 EvoMab Q2W	R5 EvoMab QM	R40 PBO Q2W	R40 PBO QM	R40 EvoMab Q2W	R40 EvoMab QM	S40 PBO Q2W	S40 PBO QM	S40 EvoMab Q2W	S40 EvoMab QM
Number of subjects analysed	56	55	56	55	110	110	55	55	56	54	109	110	58	57	113	115	56	55	111	112	56	55	112	115
Units: percent change
least squares mean (standard error)	8.54 ( 2.24 )	0.35 ( 2.6 )	-23.88 ( 2.34 )	-18.98 ( 2.57 )	-61.41 ( 1.61 )	-62.47 ( 1.83 )	13.12 ( 3.99 )	9.76 ( 3.39 )	-16.85 ( 3.88 )	-21.25 ( 3.42 )	-61.8 ( 2.77 )	-65.05 ( 2.42 )	7.55 ( 2.39 )	2.79 ( 2.5 )	-59.33 ( 1.74 )	-63.79 ( 1.76 )	6.57 ( 3.11 )	-0.02 ( 3.51 )	-59.08 ( 2.23 )	-62.94 ( 2.44 )	3.26 ( 3.4 )	6 ( 4.8 )	-66.17 ( 2.93 )	-62.45 ( 3.85 )

A10: Evolocumab Q2W vs Placebo Q2W

Statistical analysis description

The null hypothesis was that there was no difference in the mean percent change from Baseline at Weeks 10 and 12 in LDL-C between evolocumab and placebo, and the alternative hypothesis was that a mean difference did exist.

Comparison groups

A10 PBO Q2W v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[15]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-69.95

Confidence interval

level

95%

sides

2-sided

lower limit

-75.38

upper limit

-64.51

Variability estimate

Standard error of the mean

Dispersion value

2.76

Notes
[15] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Placebo QM

Statistical analysis description

Comparison groups

A10 PBO QM v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[16]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-62.82

Confidence interval

level

95%

sides

2-sided

lower limit

-69.06

upper limit

-56.57

Variability estimate

Standard error of the mean

Dispersion value

3.17

Notes
[16] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab Q2W vs Ezetimibe (Q2W)

Statistical analysis description

The null hypothesis was that there was no mean difference in the mean percent change from Baseline at Weeks 10 and 12 in LDL-C between evolocumab and ezetimibe, and the alternative hypothesis was that a mean difference did exist.

Comparison groups

A10 EZE (Q2W) v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[17]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-37.53

Confidence interval

level

95%

sides

2-sided

lower limit

-43.03

upper limit

-32.03

Variability estimate

Standard error of the mean

Dispersion value

2.79

Notes
[17] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Ezetimibe (QM)

Statistical analysis description

Comparison groups

A10 EZE (QM) v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[18]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-43.49

Confidence interval

level

95%

sides

2-sided

lower limit

-49.7

upper limit

-37.28

Variability estimate

Standard error of the mean

Dispersion value

3.15

Notes
[18] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Placebo Q2W

Statistical analysis description

Comparison groups

A80 PBO Q2W v A80 EvoMab Q2W

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[19]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-74.92

Confidence interval

level

95%

sides

2-sided

lower limit

-84.49

upper limit

-65.35

Variability estimate

Standard error of the mean

Dispersion value

4.85

Notes
[19] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Placebo QM

Statistical analysis description

Comparison groups

A80 PBO QM v A80 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[20]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-74.81

Confidence interval

level

95%

sides

2-sided

lower limit

-83

upper limit

-66.62

Variability estimate

Standard error of the mean

Dispersion value

4.15

Notes
[20] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Ezetimibe (Q2W)

Statistical analysis description

Comparison groups

A80 EZE (Q2W) v A80 EvoMab Q2W

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[21]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-44.95

Confidence interval

level

95%

sides

2-sided

lower limit

-54.32

upper limit

-35.57

Variability estimate

Standard error of the mean

Dispersion value

4.75

Notes
[21] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Ezetimibe (QM)

Statistical analysis description

Comparison groups

A80 EZE (QM) v A80 EvoMab QM

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[22]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-43.81

Confidence interval

level

95%

sides

2-sided

lower limit

-52.06

upper limit

-35.55

Variability estimate

Standard error of the mean

Dispersion value

4.19

Notes
[22] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab Q2W vs Placebo Q2W

Statistical analysis description

Comparison groups

R5 PBO Q2W v R5 EvoMab Q2W

Number of subjects included in analysis

171

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[23]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-66.88

Confidence interval

level

95%

sides

2-sided

lower limit

-72.67

upper limit

-61.08

Variability estimate

Standard error of the mean

Dispersion value

2.93

Notes
[23] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab QM vs Placebo QM

Statistical analysis description

The null hypothesis was that there was no difference in the mean percent change from Baseline at Weeks 10 and 12 between evolocumab and placebo, and the alternative hypothesis was that a mean difference did exist.

Comparison groups

R5 PBO QM v R5 EvoMab QM

Number of subjects included in analysis

172

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[24]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-66.58

Confidence interval

level

95%

sides

2-sided

lower limit

-72.6

upper limit

-60.56

Variability estimate

Standard error of the mean

Dispersion value

3.05

Notes
[24] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab Q2W vs Placebo Q2W

Statistical analysis description

Comparison groups

R40 PBO Q2W v R40 EvoMab Q2W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[25]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-65.66

Confidence interval

level

95%

sides

2-sided

lower limit

-73.19

upper limit

-58.12

Variability estimate

Standard error of the mean

Dispersion value

3.81

Notes
[25] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab QM vs Placebo QM

Statistical analysis description

Comparison groups

R40 PBO QM v R40 EvoMab QM

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[26]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-62.91

Confidence interval

level

95%

sides

2-sided

lower limit

-71.37

upper limit

-54.46

Variability estimate

Standard error of the mean

Dispersion value

4.27

Notes
[26] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab Q2W vs Placebo Q2W

Statistical analysis description

Comparison groups

S40 PBO Q2W v S40 EvoMab Q2W

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[27]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-69.43

Confidence interval

level

95%

sides

2-sided

lower limit

-74.86

upper limit

-64.01

Variability estimate

Standard error of the mean

Dispersion value

2.74

Notes
[27] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab QM vs Placebo QM

Statistical analysis description

Comparison groups

S40 PBO QM v S40 EvoMab QM

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[28]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-68.45

Confidence interval

level

95%

sides

2-sided

lower limit

-76.68

upper limit

-60.22

Variability estimate

Standard error of the mean

Dispersion value

4.17

Notes
[28] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

Secondary: Mean Change From Baseline in LDL-C at Weeks 10 and 12

Top of page

End point title

Mean Change From Baseline in LDL-C at Weeks 10 and 12

End point description

End point type

Secondary

End point timeframe

Baseline and Weeks 10 and 12

End point values	A10 PBO Q2W	A10 PBO QM	A10 EZE (Q2W)	A10 EZE (QM)	A10 EvoMab Q2W	A10 EvoMab QM	A80 PBO Q2W	A80 PBO QM	A80 EZE (Q2W)	A80 EZE (QM)	A80 EvoMab Q2W	A80 EvoMab QM	R5 PBO Q2W	R5 PBO QM	R5 EvoMab Q2W	R5 EvoMab QM	R40 PBO Q2W	R40 PBO QM	R40 EvoMab Q2W	R40 EvoMab QM	S40 PBO Q2W	S40 PBO QM	S40 EvoMab Q2W	S40 EvoMab QM
Number of subjects analysed	56	55	56	55	110	110	55	55	56	54	109	110	58	57	113	115	56	55	111	112	56	55	112	115
Units: mg/dL
least squares mean (standard error)	6.8 ( 3.7 )	-0.4 ( 4.4 )	-32.4 ( 3.8 )	-25.1 ( 4.3 )	-76.8 ( 2.7 )	-80.1 ( 3.1 )	11 ( 5 )	5.5 ( 3.7 )	-13 ( 4.9 )	-21.3 ( 3.7 )	-58.8 ( 3.5 )	-60.1 ( 2.6 )	6.5 ( 3.5 )	0.1 ( 4.2 )	-68.9 ( 2.5 )	-77.8 ( 3 )	3.4 ( 3 )	-4.8 ( 4.2 )	-52.3 ( 2.2 )	-55.3 ( 2.9 )	-5.7 ( 5.2 )	1.7 ( 6.5 )	-83.8 ( 4.5 )	-78.4 ( 5.1 )

A10: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A10 PBO Q2W v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[29]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-83.6

Confidence interval

level

95%

sides

2-sided

lower limit

-92.6

upper limit

-74.6

Variability estimate

Standard error of the mean

Dispersion value

4.5

Notes
[29] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Placebo QM

Comparison groups

A10 PBO QM v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[30]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-79.7

Confidence interval

level

95%

sides

2-sided

lower limit

-90.2

upper limit

-69.2

Variability estimate

Standard error of the mean

Dispersion value

5.3

Notes
[30] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A10 EZE (Q2W) v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[31]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-44.4

Confidence interval

level

95%

sides

2-sided

lower limit

-53.4

upper limit

-35.3

Variability estimate

Standard error of the mean

Dispersion value

4.4

Notes
[31] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A10 EZE (QM) v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[32]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-55

Confidence interval

level

95%

sides

2-sided

lower limit

-65.4

upper limit

-44.6

Variability estimate

Standard error of the mean

Dispersion value

5.3

Notes
[32] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A80 PBO Q2W v A80 EvoMab Q2W

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[33]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-69.9

Confidence interval

level

95%

sides

2-sided

lower limit

-81.9

upper limit

-57.8

Variability estimate

Standard error of the mean

Dispersion value

6.1

Notes
[33] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Placebo QM

Comparison groups

A80 PBO QM v A80 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[34]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-65.6

Confidence interval

level

95%

sides

2-sided

lower limit

-74.5

upper limit

-56.7

Variability estimate

Standard error of the mean

Dispersion value

4.5

Notes
[34] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A80 EZE (Q2W) v A80 EvoMab Q2W

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001 ^[35]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-45.8

Confidence interval

level

95%

sides

2-sided

lower limit

-57.7

upper limit

-33.9

Variability estimate

Standard error of the mean

Dispersion value

Notes
[35] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A80 EZE (QM) v A80 EvoMab QM

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[36]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-38.8

Confidence interval

level

95%

sides

2-sided

lower limit

-47.8

upper limit

-29.9

Variability estimate

Standard error of the mean

Dispersion value

4.5

Notes
[36] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R5 PBO Q2W v R5 EvoMab Q2W

Number of subjects included in analysis

171

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[37]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-75.4

Confidence interval

level

95%

sides

2-sided

lower limit

-83.9

upper limit

-67

Variability estimate

Standard error of the mean

Dispersion value

4.3

Notes
[37] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab QM vs Placebo QM

Comparison groups

R5 PBO QM v R5 EvoMab QM

Number of subjects included in analysis

172

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[38]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-77.9

Confidence interval

level

95%

sides

2-sided

lower limit

-88

upper limit

-67.8

Variability estimate

Standard error of the mean

Dispersion value

5.1

Notes
[38] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R40 PBO Q2W v R40 EvoMab Q2W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[39]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-55.8

Confidence interval

level

95%

sides

2-sided

lower limit

-63.1

upper limit

-48.4

Variability estimate

Standard error of the mean

Dispersion value

3.7

Notes
[39] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab QM vs Placebo QM

Comparison groups

R40 PBO QM v R40 EvoMab QM

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[40]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-50.6

Confidence interval

level

95%

sides

2-sided

lower limit

-60.6

upper limit

-40.6

Variability estimate

Standard error of the mean

Dispersion value

5.1

Notes
[40] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

S40 PBO Q2W v S40 EvoMab Q2W

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[41]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-78.1

Confidence interval

level

95%

sides

2-sided

lower limit

-86.2

upper limit

-70

Variability estimate

Standard error of the mean

Dispersion value

4.1

Notes
[41] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab QM vs Placebo QM

Comparison groups

S40 PBO QM v S40 EvoMab QM

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[42]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-80.1

Confidence interval

level

95%

sides

2-sided

lower limit

-91.7

upper limit

-68.6

Variability estimate

Standard error of the mean

Dispersion value

5.8

Notes
[42] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

Secondary: Change From Baseline in LDL-C at Week 12

Top of page

End point title

Change From Baseline in LDL-C at Week 12

End point description

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	A10 PBO Q2W	A10 PBO QM	A10 EZE (Q2W)	A10 EZE (QM)	A10 EvoMab Q2W	A10 EvoMab QM	A80 PBO Q2W	A80 PBO QM	A80 EZE (Q2W)	A80 EZE (QM)	A80 EvoMab Q2W	A80 EvoMab QM	R5 PBO Q2W	R5 PBO QM	R5 EvoMab Q2W	R5 EvoMab QM	R40 PBO Q2W	R40 PBO QM	R40 EvoMab Q2W	R40 EvoMab QM	S40 PBO Q2W	S40 PBO QM	S40 EvoMab Q2W	S40 EvoMab QM
Number of subjects analysed	56	55	56	55	110	110	55	55	56	54	109	110	58	57	113	115	56	55	111	112	56	55	112	115
Units: mg/dL
least squares mean (standard error)	8.6 ( 4 )	0.8 ( 4.5 )	-30.1 ( 4.1 )	-23.3 ( 4.5 )	-77 ( 2.9 )	-75.1 ( 3.2 )	12.7 ( 5.3 )	7 ( 4.1 )	-9.9 ( 5.2 )	-19.5 ( 4.1 )	-59 ( 3.7 )	-54.8 ( 2.9 )	7.8 ( 3.8 )	2.4 ( 4.4 )	-69.2 ( 2.7 )	-73.3 ( 3.1 )	5.1 ( 3.2 )	-2 ( 4.7 )	-52.1 ( 2.3 )	-46.7 ( 3.3 )	-4.5 ( 5.3 )	-0.6 ( 6.6 )	-83.5 ( 4.6 )	-72.5 ( 5.2 )

A10: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A10 PBO Q2W v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[43]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-85.5

Confidence interval

level

95%

sides

2-sided

lower limit

-95.2

upper limit

-75.9

Variability estimate

Standard error of the mean

Dispersion value

4.9

Notes
[43] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Placebo QM

Comparison groups

A10 PBO QM v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[44]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-75.8

Confidence interval

level

95%

sides

2-sided

lower limit

-86.8

upper limit

-64.9

Variability estimate

Standard error of the mean

Dispersion value

5.5

Notes
[44] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A10 EZE (Q2W) v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[45]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-46.8

Confidence interval

level

95%

sides

2-sided

lower limit

-56.6

upper limit

-37.1

Variability estimate

Standard error of the mean

Dispersion value

4.9

Notes
[45] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A10 EZE (QM) v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[46]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-51.7

Confidence interval

level

95%

sides

2-sided

lower limit

-62.6

upper limit

-40.9

Variability estimate

Standard error of the mean

Dispersion value

5.5

Notes
[46] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A80 PBO Q2W v A80 EvoMab Q2W

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[47]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-71.7

Confidence interval

level

95%

sides

2-sided

lower limit

-84.4

upper limit

-59

Variability estimate

Standard error of the mean

Dispersion value

6.4

Notes
[47] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Placebo QM

Comparison groups

A80 PBO QM v A80 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[48]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-61.8

Confidence interval

level

95%

sides

2-sided

lower limit

-71.6

upper limit

-52

Variability estimate

Standard error of the mean

Dispersion value

Notes
[48] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A80 EZE (Q2W) v A80 EvoMab Q2W

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[49]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-49

Confidence interval

level

95%

sides

2-sided

lower limit

-61.5

upper limit

-36.6

Variability estimate

Standard error of the mean

Dispersion value

6.3

Notes
[49] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A80 EZE (QM) v A80 EvoMab QM

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[50]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-35.3

Confidence interval

level

95%

sides

2-sided

lower limit

-45.2

upper limit

-25.5

Variability estimate

Standard error of the mean

Dispersion value

Notes
[50] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R5 PBO Q2W v R5 EvoMab Q2W

Number of subjects included in analysis

171

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[51]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-77.1

Confidence interval

level

95%

sides

2-sided

lower limit

-86.2

upper limit

-67.9

Variability estimate

Standard error of the mean

Dispersion value

4.6

Notes
[51] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab QM vs Placebo QM

Comparison groups

R5 PBO QM v R5 EvoMab QM

Number of subjects included in analysis

172

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[52]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-75.8

Confidence interval

level

95%

sides

2-sided

lower limit

-86.3

upper limit

-65.3

Variability estimate

Standard error of the mean

Dispersion value

5.3

Notes
[52] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R40 PBO Q2W v R40 EvoMab Q2W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[53]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-57.2

Confidence interval

level

95%

sides

2-sided

lower limit

-65.1

upper limit

-49.4

Variability estimate

Standard error of the mean

Dispersion value

Notes
[53] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab QM vs Placebo QM

Comparison groups

R40 PBO QM v R40 EvoMab QM

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[54]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-44.6

Confidence interval

level

95%

sides

2-sided

lower limit

-55.9

upper limit

-33.4

Variability estimate

Standard error of the mean

Dispersion value

5.7

Notes
[54] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

S40 PBO Q2W v S40 EvoMab Q2W

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[55]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-79

Confidence interval

level

95%

sides

2-sided

lower limit

-87.5

upper limit

-70.4

Variability estimate

Standard error of the mean

Dispersion value

4.3

Notes
[55] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab QM vs Placebo QM

Comparison groups

S40 PBO QM v S40 EvoMab QM

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[56]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-71.9

Confidence interval

level

95%

sides

2-sided

lower limit

-83.8

upper limit

-60

Variability estimate

Standard error of the mean

Dispersion value

Notes
[56] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

Secondary: Mean Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (non-HDL-C) at Weeks 10 and 12

Top of page

End point title

Mean Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (non-HDL-C) at Weeks 10 and 12

End point description

Efficacy analyses were performed on the full analysis set. Least squares (LS) means are from a repeated measures linear effects model; missing values were not imputed.

End point type

Secondary

End point timeframe

Baseline and Weeks 10 and 12

End point values	A10 PBO Q2W	A10 PBO QM	A10 EZE (Q2W)	A10 EZE (QM)	A10 EvoMab Q2W	A10 EvoMab QM	A80 PBO Q2W	A80 PBO QM	A80 EZE (Q2W)	A80 EZE (QM)	A80 EvoMab Q2W	A80 EvoMab QM	R5 PBO Q2W	R5 PBO QM	R5 EvoMab Q2W	R5 EvoMab QM	R40 PBO Q2W	R40 PBO QM	R40 EvoMab Q2W	R40 EvoMab QM	S40 PBO Q2W	S40 PBO QM	S40 EvoMab Q2W	S40 EvoMab QM
Number of subjects analysed	56	55	56	55	110	110	55	55	56	54	109	110	58	57	113	115	56	55	111	112	56	55	112	115
Units: percent change
least squares mean (standard error)	6.8 ( 2.07 )	1.28 ( 2.44 )	-20.71 ( 2.15 )	-16.56 ( 2.41 )	-53.48 ( 1.48 )	-56.09 ( 1.71 )	10.74 ( 3.59 )	8.45 ( 3.13 )	-16.19 ( 3.49 )	-18.79 ( 3.16 )	-54.44 ( 2.49 )	-56.31 ( 2.23 )	7.02 ( 2.11 )	3.73 ( 2.32 )	-52.59 ( 1.54 )	-55.47 ( 1.64 )	6.19 ( 2.61 )	1.58 ( 2.9 )	-52.08 ( 1.88 )	-55.72 ( 2.01 )	0.74 ( 3.23 )	6.81 ( 4.35 )	-59.33 ( 2.79 )	-56.01 ( 3.49 )

A10: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A10 PBO Q2W v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[57]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-60.28

Confidence interval

level

95%

sides

2-sided

lower limit

-65.29

upper limit

-55.27

Variability estimate

Standard error of the mean

Dispersion value

2.54

Notes
[57] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Placebo QM

Comparison groups

A10 PBO QM v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[58]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-57.37

Confidence interval

level

95%

sides

2-sided

lower limit

-63.23

upper limit

-51.51

Variability estimate

Standard error of the mean

Dispersion value

2.97

Notes
[58] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A10 EZE (Q2W) v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[59]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-32.77

Confidence interval

level

95%

sides

2-sided

lower limit

-37.84

upper limit

-27.7

Variability estimate

Standard error of the mean

Dispersion value

2.57

Notes
[59] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A10 EZE (QM) v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[60]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-39.53

Confidence interval

level

95%

sides

2-sided

lower limit

-45.34

upper limit

-33.71

Variability estimate

Standard error of the mean

Dispersion value

2.95

Notes
[60] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A80 PBO Q2W v A80 EvoMab Q2W

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[61]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-65.17

Confidence interval

level

95%

sides

2-sided

lower limit

-73.78

upper limit

-56.56

Variability estimate

Standard error of the mean

Dispersion value

4.37

Notes
[61] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Placebo QM

Comparison groups

A80 PBO QM v A80 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[62]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-64.76

Confidence interval

level

95%

sides

2-sided

lower limit

-72.32

upper limit

-57.19

Variability estimate

Standard error of the mean

Dispersion value

3.84

Notes
[62] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A80 EZE (Q2W) v A80 EvoMab Q2W

Number of subjects included in analysis

165

Analysis specification

Post-hoc

Analysis type

superiority

P-value

< 0.001 ^[63]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-38.25

Confidence interval

level

95%

sides

2-sided

lower limit

-46.68

upper limit

-29.81

Variability estimate

Standard error of the mean

Dispersion value

4.28

Notes
[63] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A80 EZE (QM) v A80 EvoMab QM

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[64]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-37.52

Confidence interval

level

95%

sides

2-sided

lower limit

-45.15

upper limit

-29.9

Variability estimate

Standard error of the mean

Dispersion value

3.87

Notes
[64] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R5 PBO Q2W v R5 EvoMab Q2W

Number of subjects included in analysis

171

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[65]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-59.61

Confidence interval

level

95%

sides

2-sided

lower limit

-64.73

upper limit

-54.48

Variability estimate

Standard error of the mean

Dispersion value

2.6

Notes
[65] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab QM vs Placebo QM

Comparison groups

R5 PBO QM v R5 EvoMab QM

Number of subjects included in analysis

172

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[66]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-59.2

Confidence interval

level

95%

sides

2-sided

lower limit

-64.8

upper limit

-53.6

Variability estimate

Standard error of the mean

Dispersion value

2.83

Notes
[66] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R40 PBO Q2W v R40 EvoMab Q2W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[67]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-58.27

Confidence interval

level

95%

sides

2-sided

lower limit

-64.6

upper limit

-51.94

Variability estimate

Standard error of the mean

Dispersion value

3.2

Notes
[67] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab QM vs Placebo QM

Comparison groups

R40 PBO QM v R40 EvoMab QM

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[68]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-57.31

Confidence interval

level

95%

sides

2-sided

lower limit

-64.29

upper limit

-50.32

Variability estimate

Standard error of the mean

Dispersion value

3.53

Notes
[68] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

S40 PBO Q2W v S40 EvoMab Q2W

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[69]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-60.06

Confidence interval

level

95%

sides

2-sided

lower limit

-65.18

upper limit

-54.94

Variability estimate

Standard error of the mean

Dispersion value

2.59

Notes
[69] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab QM vs Placebo QM

Comparison groups

S40 PBO QM v S40 EvoMab QM

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[70]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-62.82

Confidence interval

level

95%

sides

2-sided

lower limit

-70.22

upper limit

-55.42

Variability estimate

Standard error of the mean

Dispersion value

3.75

Notes
[70] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

Secondary: Percent Change From Baseline in non-HDL-C at Week 12

Top of page

End point title

Percent Change From Baseline in non-HDL-C at Week 12

End point description

Efficacy analyses were performed on the full analysis set. Least squares (LS) means are from a repeated measures linear effects model; missing values were not imputed.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	A10 PBO Q2W	A10 PBO QM	A10 EZE (Q2W)	A10 EZE (QM)	A10 EvoMab Q2W	A10 EvoMab QM	A80 PBO Q2W	A80 PBO QM	A80 EZE (Q2W)	A80 EZE (QM)	A80 EvoMab Q2W	A80 EvoMab QM	R5 PBO Q2W	R5 PBO QM	R5 EvoMab Q2W	R5 EvoMab QM	R40 PBO Q2W	R40 PBO QM	R40 EvoMab Q2W	R40 EvoMab QM	S40 PBO Q2W	S40 PBO QM	S40 EvoMab Q2W	S40 EvoMab QM
Number of subjects analysed	56	55	56	55	110	110	55	55	56	54	109	110	58	57	113	115	56	55	111	112	56	55	112	115
Units: percent change
least squares mean (standard error)	8.25 ( 2.32 )	2.43 ( 2.69 )	-18.27 ( 2.4 )	-14.78 ( 2.65 )	-53.39 ( 1.66 )	-52.2 ( 1.9 )	11.79 ( 3.87 )	9.95 ( 3.51 )	-14.34 ( 3.75 )	-17.26 ( 3.52 )	-54.84 ( 2.66 )	-50.05 ( 2.5 )	7.92 ( 2.4 )	5.85 ( 2.42 )	-52.04 ( 1.74 )	-51.57 ( 1.72 )	8.61 ( 3.04 )	3.35 ( 3.53 )	-50.97 ( 2.18 )	-46.42 ( 2.45 )	1.89 ( 3.38 )	5.66 ( 4.53 )	-59.02 ( 2.87 )	-50.96 ( 3.6 )

A10: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A10 PBO Q2W v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[71]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-61.64

Confidence interval

level

95%

sides

2-sided

lower limit

-67.25

upper limit

-56.03

Variability estimate

Standard error of the mean

Dispersion value

2.84

Notes
[71] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Placebo QM

Comparison groups

A10 PBO QM v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[72]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-54.93

Confidence interval

level

95%

sides

2-sided

lower limit

-61.4

upper limit

-48.46

Variability estimate

Standard error of the mean

Dispersion value

3.28

Notes
[72] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A10 EZE (Q2W) v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[73]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-35.11

Confidence interval

level

95%

sides

2-sided

lower limit

-40.79

upper limit

-29.44

Variability estimate

Standard error of the mean

Dispersion value

2.88

Notes
[73] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A10 EZE (QM) v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[74]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-37.72

Confidence interval

level

95%

sides

2-sided

lower limit

-44.15

upper limit

-31.3

Variability estimate

Standard error of the mean

Dispersion value

3.26

Notes
[74] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A80 PBO Q2W v A80 EvoMab Q2W

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[75]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-66.64

Confidence interval

level

95%

sides

2-sided

lower limit

-75.88

upper limit

-57.39

Variability estimate

Standard error of the mean

Dispersion value

4.69

Notes
[75] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Placebo QM

Comparison groups

A80 PBO QM v A80 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[76]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-60.01

Confidence interval

level

95%

sides

2-sided

lower limit

-68.49

upper limit

-51.52

Variability estimate

Standard error of the mean

Dispersion value

4.3

Notes
[76] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A80 EZE (Q2W) v A80 EvoMab Q2W

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[77]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-40.51

Confidence interval

level

95%

sides

2-sided

lower limit

-49.55

upper limit

-31.47

Variability estimate

Standard error of the mean

Dispersion value

4.59

Notes
[77] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A80 EZE (QM) v A80 EvoMab QM

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[78]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-32.79

Confidence interval

level

95%

sides

2-sided

lower limit

-41.3

upper limit

-24.28

Variability estimate

Standard error of the mean

Dispersion value

4.32

Notes
[78] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R5 PBO Q2W v R5 EvoMab Q2W

Number of subjects included in analysis

171

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[79]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-59.96

Confidence interval

level

95%

sides

2-sided

lower limit

-65.78

upper limit

-54.13

Variability estimate

Standard error of the mean

Dispersion value

2.95

Notes
[79] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab QM vs Placebo QM

Comparison groups

R5 PBO QM v R5 EvoMab QM

Number of subjects included in analysis

172

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[80]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-57.42

Confidence interval

level

95%

sides

2-sided

lower limit

-63.27

upper limit

-51.57

Variability estimate

Standard error of the mean

Dispersion value

2.96

Notes
[80] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R40 PBO Q2W v R40 EvoMab Q2W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[81]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-59.58

Confidence interval

level

95%

sides

2-sided

lower limit

-66.95

upper limit

-52.21

Variability estimate

Standard error of the mean

Dispersion value

3.73

Notes
[81] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab QM vs Placebo QM

Comparison groups

R40 PBO QM v R40 EvoMab QM

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[82]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-49.76

Confidence interval

level

95%

sides

2-sided

lower limit

-58.26

upper limit

-41.27

Variability estimate

Standard error of the mean

Dispersion value

4.3

Notes
[82] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

S40 PBO Q2W v S40 EvoMab Q2W

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[83]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-60.91

Confidence interval

level

95%

sides

2-sided

lower limit

-66.57

upper limit

-55.24

Variability estimate

Standard error of the mean

Dispersion value

2.87

Notes
[83] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab QM vs Placebo QM

Comparison groups

S40 PBO QM v S40 EvoMab QM

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[84]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-56.63

Confidence interval

level

95%

sides

2-sided

lower limit

-64.63

upper limit

-48.62

Variability estimate

Standard error of the mean

Dispersion value

4.06

Notes
[84] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

Secondary: Mean Percent Change From Baseline in Apolipoprotein B at Weeks 10 and 12

Top of page

End point title

Mean Percent Change From Baseline in Apolipoprotein B at Weeks 10 and 12

End point description

Efficacy analyses were performed on the full analysis set. Least squares (LS) means are from a repeated measures linear effects model; missing values were not imputed.

End point type

Secondary

End point timeframe

Baseline and Weeks 10 and 12

End point values	A10 PBO Q2W	A10 PBO QM	A10 EZE (Q2W)	A10 EZE (QM)	A10 EvoMab Q2W	A10 EvoMab QM	A80 PBO Q2W	A80 PBO QM	A80 EZE (Q2W)	A80 EZE (QM)	A80 EvoMab Q2W	A80 EvoMab QM	R5 PBO Q2W	R5 PBO QM	R5 EvoMab Q2W	R5 EvoMab QM	R40 PBO Q2W	R40 PBO QM	R40 EvoMab Q2W	R40 EvoMab QM	S40 PBO Q2W	S40 PBO QM	S40 EvoMab Q2W	S40 EvoMab QM
Number of subjects analysed	56	55	56	55	110	110	55	55	56	54	109	110	58	57	113	115	56	55	111	112	56	55	112	115
Units: percent change
least squares mean (standard error)	7.55 ( 1.89 )	0.81 ( 2.19 )	-17.29 ( 2 )	-11.43 ( 2.2 )	-50.95 ( 1.38 )	-51.44 ( 1.52 )	10.2 ( 3.02 )	5.48 ( 2.83 )	-14.22 ( 2.98 )	-13.62 ( 2.87 )	-49.14 ( 2.13 )	-53.26 ( 2.02 )	5.07 ( 1.97 )	2.54 ( 1.89 )	-49.79 ( 1.46 )	-53.59 ( 1.32 )	3.71 ( 2.46 )	1.98 ( 2.57 )	-47.07 ( 1.76 )	-52.95 ( 1.76 )	-0.31 ( 3.02 )	2.49 ( 4.67 )	-55.65 ( 2.63 )	-54.37 ( 3.93 )

A10: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A10 PBO Q2W v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[85]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-58.49

Confidence interval

level

95%

sides

2-sided

lower limit

-63.1

upper limit

-53.89

Variability estimate

Standard error of the mean

Dispersion value

2.34

Notes
[85] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Placebo QM

Comparison groups

A10 PBO QM v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[86]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-52.25

Confidence interval

level

95%

sides

2-sided

lower limit

-57.49

upper limit

-47.01

Variability estimate

Standard error of the mean

Dispersion value

2.66

Notes
[86] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A10 EZE (Q2W) v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[87]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-33.66

Confidence interval

level

95%

sides

2-sided

lower limit

-38.33

upper limit

-28.98

Variability estimate

Standard error of the mean

Dispersion value

2.37

Notes
[87] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A10 EZE (QM) v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[88]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-40.01

Confidence interval

level

95%

sides

2-sided

lower limit

-45.27

upper limit

-34.74

Variability estimate

Standard error of the mean

Dispersion value

2.67

Notes
[88] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A80 PBO Q2W v A80 EvoMab Q2W

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[89]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-59.34

Confidence interval

level

95%

sides

2-sided

lower limit

-66.61

upper limit

-52.07

Variability estimate

Standard error of the mean

Dispersion value

3.69

Notes
[89] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Placebo QM

Comparison groups

A80 PBO QM v A80 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[90]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-58.74

Confidence interval

level

95%

sides

2-sided

lower limit

-65.56

upper limit

-51.93

Variability estimate

Standard error of the mean

Dispersion value

3.46

Notes
[90] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A80 EZE (Q2W) v A80 EvoMab Q2W

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[91]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-34.92

Confidence interval

level

95%

sides

2-sided

lower limit

-42.09

upper limit

-27.75

Variability estimate

Standard error of the mean

Dispersion value

3.64

Notes
[91] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A80 EZE (QM) v A80 EvoMab QM

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[92]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-39.64

Confidence interval

level

95%

sides

2-sided

lower limit

-46.57

upper limit

-32.71

Variability estimate

Standard error of the mean

Dispersion value

3.52

Notes
[92] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R5 PBO Q2W v R5 EvoMab Q2W

Number of subjects included in analysis

171

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[93]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-54.86

Confidence interval

level

95%

sides

2-sided

lower limit

-59.66

upper limit

-50.05

Variability estimate

Standard error of the mean

Dispersion value

2.43

Notes
[93] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab QM vs Placebo QM

Comparison groups

R5 PBO QM v R5 EvoMab QM

Number of subjects included in analysis

172

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[94]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-56.14

Confidence interval

level

95%

sides

2-sided

lower limit

-60.66

upper limit

-51.61

Variability estimate

Standard error of the mean

Dispersion value

2.29

Notes
[94] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R40 PBO Q2W v R40 EvoMab Q2W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[95]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-50.78

Confidence interval

level

95%

sides

2-sided

lower limit

-56.72

upper limit

-44.83

Variability estimate

Standard error of the mean

Dispersion value

3.01

Notes
[95] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab QM vs Placebo QM

Comparison groups

R40 PBO QM v R40 EvoMab QM

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[96]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-54.94

Confidence interval

level

95%

sides

2-sided

lower limit

-61.11

upper limit

-48.76

Variability estimate

Standard error of the mean

Dispersion value

3.12

Notes
[96] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

S40 PBO Q2W v S40 EvoMab Q2W

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[97]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-55.34

Confidence interval

level

95%

sides

2-sided

lower limit

-59.94

upper limit

-50.74

Variability estimate

Standard error of the mean

Dispersion value

2.33

Notes
[97] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab QM vs Placebo QM

Comparison groups

S40 PBO QM v S40 EvoMab QM

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[98]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-56.87

Confidence interval

level

95%

sides

2-sided

lower limit

-63.27

upper limit

-50.46

Variability estimate

Standard error of the mean

Dispersion value

3.24

Notes
[98] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

Secondary: Percent Change From Baseline in Apolipoprotein B at Week 12

Top of page

End point title

Percent Change From Baseline in Apolipoprotein B at Week 12

End point description

Efficacy analyses were performed on the full analysis set. Least squares (LS) means are from a repeated measures linear effects model; missing values were not imputed.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	A10 PBO Q2W	A10 PBO QM	A10 EZE (Q2W)	A10 EZE (QM)	A10 EvoMab Q2W	A10 EvoMab QM	A80 PBO Q2W	A80 PBO QM	A80 EZE (Q2W)	A80 EZE (QM)	A80 EvoMab Q2W	A80 EvoMab QM	R5 PBO Q2W	R5 PBO QM	R5 EvoMab Q2W	R5 EvoMab QM	R40 PBO Q2W	R40 PBO QM	R40 EvoMab Q2W	R40 EvoMab QM	S40 PBO Q2W	S40 PBO QM	S40 EvoMab Q2W	S40 EvoMab QM
Number of subjects analysed	56	55	56	55	110	110	55	55	56	54	109	110	58	57	113	115	56	55	111	112	56	55	112	115
Units: percent change
least squares mean (standard error)	7.89 ( 2.16 )	0.21 ( 2.43 )	-15.98 ( 2.26 )	-10.95 ( 2.44 )	-50.9 ( 1.56 )	-47.15 ( 1.7 )	11.64 ( 3.28 )	6.54 ( 3.22 )	-12.31 ( 3.2 )	-12.16 ( 3.24 )	-49.77 ( 2.28 )	-46.47 ( 2.31 )	6.35 ( 2.1 )	4.63 ( 2.11 )	-50.15 ( 1.54 )	-48.58 ( 1.49 )	4.91 ( 2.71 )	3.24 ( 3.13 )	-45.61 ( 1.93 )	-43.71 ( 2.13 )	0.35 ( 3.17 )	3.57 ( 4.74 )	-55.95 ( 2.72 )	-49.16 ( 3.97 )

A10: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A10 PBO Q2W v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[99]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-58.79

Confidence interval

level

95%

sides

2-sided

lower limit

-64.03

upper limit

-53.55

Variability estimate

Standard error of the mean

Dispersion value

2.66

Notes
[99] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Placebo QM

Comparison groups

A10 PBO QM v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[100]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-47.36

Confidence interval

level

95%

sides

2-sided

lower limit

-53.2

upper limit

-41.52

Variability estimate

Standard error of the mean

Dispersion value

2.96

Notes
[100] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A10 EZE (Q2W) v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[101]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-34.92

Confidence interval

level

95%

sides

2-sided

lower limit

-40.23

upper limit

-29.6

Variability estimate

Standard error of the mean

Dispersion value

2.69

Notes
[101] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A10 EZE (QM) v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[102]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-36.21

Confidence interval

level

95%

sides

2-sided

lower limit

-42.06

upper limit

-30.35

Variability estimate

Standard error of the mean

Dispersion value

2.97

Notes
[102] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A80 PBO Q2W v A80 EvoMab Q2W

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[103]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-61.4

Confidence interval

level

95%

sides

2-sided

lower limit

-69.27

upper limit

-53.54

Variability estimate

Standard error of the mean

Dispersion value

3.99

Notes
[103] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Placebo QM

Comparison groups

A80 PBO QM v A80 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[104]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-53.01

Confidence interval

level

95%

sides

2-sided

lower limit

-60.77

upper limit

-45.25

Variability estimate

Standard error of the mean

Dispersion value

3.93

Notes
[104] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A80 EZE (Q2W) v A80 EvoMab Q2W

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[105]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-37.45

Confidence interval

level

95%

sides

2-sided

lower limit

-45.17

upper limit

-29.74

Variability estimate

Standard error of the mean

Dispersion value

3.91

Notes
[105] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A80 EZE (QM) v A80 EvoMab QM

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[106]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-34.31

Confidence interval

level

95%

sides

2-sided

lower limit

-42.15

upper limit

-26.47

Variability estimate

Standard error of the mean

Dispersion value

3.98

Notes
[106] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R5 PBO Q2W v R5 EvoMab Q2W

Number of subjects included in analysis

171

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[107]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-56.5

Confidence interval

level

95%

sides

2-sided

lower limit

-61.6

upper limit

-51.4

Variability estimate

Standard error of the mean

Dispersion value

2.58

Notes
[107] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab QM vs Placebo QM

Comparison groups

R5 PBO QM v R5 EvoMab QM

Number of subjects included in analysis

172

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[108]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-53.21

Confidence interval

level

95%

sides

2-sided

lower limit

-58.29

upper limit

-48.13

Variability estimate

Standard error of the mean

Dispersion value

2.57

Notes
[108] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R40 PBO Q2W v R40 EvoMab Q2W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[109]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-50.52

Confidence interval

level

95%

sides

2-sided

lower limit

-57.06

upper limit

-43.99

Variability estimate

Standard error of the mean

Dispersion value

3.31

Notes
[109] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab QM vs Placebo QM

Comparison groups

R40 PBO QM v R40 EvoMab QM

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[110]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-46.95

Confidence interval

level

95%

sides

2-sided

lower limit

-54.43

upper limit

-39.47

Variability estimate

Standard error of the mean

Dispersion value

3.78

Notes
[110] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

S40 PBO Q2W v S40 EvoMab Q2W

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[111]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-56.3

Confidence interval

level

95%

sides

2-sided

lower limit

-61.47

upper limit

-51.14

Variability estimate

Standard error of the mean

Dispersion value

2.61

Notes
[111] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab QM vs Placebo QM

Comparison groups

S40 PBO QM v S40 EvoMab QM

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[112]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-52.73

Confidence interval

level

95%

sides

2-sided

lower limit

-59.4

upper limit

-46.06

Variability estimate

Standard error of the mean

Dispersion value

3.38

Notes
[112] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

Secondary: Mean Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Weeks 10 and 12

Top of page

End point title

Mean Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Weeks 10 and 12

End point description

Efficacy analyses were performed on the full analysis set. Least squares (LS) means are from a repeated measures linear effects model; missing values were not imputed.

End point type

Secondary

End point timeframe

Baseline and Weeks 10 and 12

End point values	A10 PBO Q2W	A10 PBO QM	A10 EZE (Q2W)	A10 EZE (QM)	A10 EvoMab Q2W	A10 EvoMab QM	A80 PBO Q2W	A80 PBO QM	A80 EZE (Q2W)	A80 EZE (QM)	A80 EvoMab Q2W	A80 EvoMab QM	R5 PBO Q2W	R5 PBO QM	R5 EvoMab Q2W	R5 EvoMab QM	R40 PBO Q2W	R40 PBO QM	R40 EvoMab Q2W	R40 EvoMab QM	S40 PBO Q2W	S40 PBO QM	S40 EvoMab Q2W	S40 EvoMab QM
Number of subjects analysed	56	55	56	55	110	110	55	55	56	54	109	110	58	57	113	115	56	55	111	112	56	55	112	115
Units: percent change
least squares mean (standard error)	5.96 ( 1.76 )	2.24 ( 2.11 )	-14.39 ( 1.83 )	-10.86 ( 2.08 )	-40.44 ( 1.26 )	-42.45 ( 1.48 )	4.26 ( 2.59 )	6.42 ( 2.34 )	-11.92 ( 2.52 )	-12.25 ( 2.35 )	-40.22 ( 1.8 )	-40.43 ( 1.66 )	5.41 ( 1.96 )	5.02 ( 2.25 )	-39.33 ( 1.43 )	-42 ( 1.59 )	4.55 ( 1.98 )	1.71 ( 2.36 )	-36.04 ( 1.42 )	-38.62 ( 1.64 )	-0.14 ( 2.79 )	5.45 ( 3.5 )	-47.2 ( 2.37 )	-43.17 ( 2.85 )

A10: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A10 PBO Q2W v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[113]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-46.41

Confidence interval

level

95%

sides

2-sided

lower limit

-50.66

upper limit

-42.15

Variability estimate

Standard error of the mean

Dispersion value

2.16

Notes
[113] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Placebo QM

Comparison groups

A10 PBO QM v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[114]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-44.69

Confidence interval

level

95%

sides

2-sided

lower limit

-49.75

upper limit

-39.63

Variability estimate

Standard error of the mean

Dispersion value

2.57

Notes
[114] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A10 EZE (Q2W) v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[115]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-26.06

Confidence interval

level

95%

sides

2-sided

lower limit

-30.36

upper limit

-21.75

Variability estimate

Standard error of the mean

Dispersion value

2.19

Notes
[115] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A10 EZE (QM) v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[116]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-31.59

Confidence interval

level

95%

sides

2-sided

lower limit

-36.61

upper limit

-26.57

Variability estimate

Standard error of the mean

Dispersion value

2.55

Notes
[116] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A80 PBO Q2W v A80 EvoMab Q2W

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[117]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-44.48

Confidence interval

level

95%

sides

2-sided

lower limit

-50.69

upper limit

-38.27

Variability estimate

Standard error of the mean

Dispersion value

3.15

Notes
[117] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Placebo QM

Comparison groups

A80 PBO QM v A80 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[118]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-46.85

Confidence interval

level

95%

sides

2-sided

lower limit

-52.48

upper limit

-41.21

Variability estimate

Standard error of the mean

Dispersion value

2.86

Notes
[118] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A80 EZE (Q2W) v A80 EvoMab Q2W

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[119]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-28.3

Confidence interval

level

95%

sides

2-sided

lower limit

-34.39

upper limit

-22.21

Variability estimate

Standard error of the mean

Dispersion value

3.09

Notes
[119] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A80 EZE (QM) v A80 EvoMab QM

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[120]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-28.18

Confidence interval

level

95%

sides

2-sided

lower limit

-33.86

upper limit

-22.5

Variability estimate

Standard error of the mean

Dispersion value

2.88

Notes
[120] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R5 PBO Q2W v R5 EvoMab Q2W

Number of subjects included in analysis

171

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[121]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-44.73

Confidence interval

level

95%

sides

2-sided

lower limit

-49.5

upper limit

-39.97

Variability estimate

Standard error of the mean

Dispersion value

2.41

Notes
[121] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab QM vs Placebo QM

Comparison groups

R5 PBO QM v R5 EvoMab QM

Number of subjects included in analysis

172

Analysis specification

Post-hoc

Analysis type

superiority

P-value

< 0.001 ^[122]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-47.01

Confidence interval

level

95%

sides

2-sided

lower limit

-52.46

upper limit

-41.57

Variability estimate

Standard error of the mean

Dispersion value

2.75

Notes
[122] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R40 PBO Q2W v R40 EvoMab Q2W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[123]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-40.59

Confidence interval

level

95%

sides

2-sided

lower limit

-45.38

upper limit

-35.79

Variability estimate

Standard error of the mean

Dispersion value

2.43

Notes
[123] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab QM vs Placebo QM

Comparison groups

R40 PBO QM v R40 EvoMab QM

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[124]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-40.33

Confidence interval

level

95%

sides

2-sided

lower limit

-46

upper limit

-34.66

Variability estimate

Standard error of the mean

Dispersion value

2.87

Notes
[124] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

S40 PBO Q2W v S40 EvoMab Q2W

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[125]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-47.05

Confidence interval

level

95%

sides

2-sided

lower limit

-51.76

upper limit

-42.35

Variability estimate

Standard error of the mean

Dispersion value

2.38

Notes
[125] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab QM vs Placebo QM

Comparison groups

S40 PBO QM v S40 EvoMab QM

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[126]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-48.62

Confidence interval

level

95%

sides

2-sided

lower limit

-54.27

upper limit

-42.98

Variability estimate

Standard error of the mean

Dispersion value

2.86

Notes
[126] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

Secondary: Mean Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12

Top of page

End point title

Mean Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12

End point description

Efficacy analyses were performed on the full analysis set. Least squares (LS) means are from a repeated measures linear effects model; missing values were not imputed.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	A10 PBO Q2W	A10 PBO QM	A10 EZE (Q2W)	A10 EZE (QM)	A10 EvoMab Q2W	A10 EvoMab QM	A80 PBO Q2W	A80 PBO QM	A80 EZE (Q2W)	A80 EZE (QM)	A80 EvoMab Q2W	A80 EvoMab QM	R5 PBO Q2W	R5 PBO QM	R5 EvoMab Q2W	R5 EvoMab QM	R40 PBO Q2W	R40 PBO QM	R40 EvoMab Q2W	R40 EvoMab QM	S40 PBO Q2W	S40 PBO QM	S40 EvoMab Q2W	S40 EvoMab QM
Number of subjects analysed	56	55	56	55	110	110	55	55	56	54	109	110	58	57	113	115	56	55	111	112	56	55	112	115
Units: percent change
least squares mean (standard error)	6.09 ( 2.02 )	2.8 ( 2.31 )	-12.14 ( 2.1 )	-9.85 ( 2.28 )	-40.74 ( 1.45 )	-40.07 ( 1.63 )	4.31 ( 2.75 )	6.18 ( 2.73 )	-10.53 ( 2.66 )	-11.06 ( 2.73 )	-40.79 ( 1.89 )	-36.25 ( 1.94 )	4.68 ( 2.28 )	6.07 ( 2.36 )	-38.57 ( 1.64 )	-39.26 ( 1.68 )	5.96 ( 2.28 )	2.69 ( 2.8 )	-35.17 ( 1.63 )	-32.3 ( 1.94 )	-0.2 ( 2.81 )	5.13 ( 3.62 )	-47.24 ( 2.38 )	-39.47 ( 2.92 )

A10: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A10 PBO Q2W v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[127]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-46.83

Confidence interval

level

95%

sides

2-sided

lower limit

-51.73

upper limit

-41.94

Variability estimate

Standard error of the mean

Dispersion value

2.48

Notes
[127] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Placebo QM

Comparison groups

A10 PBO QM v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[128]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-42.86

Confidence interval

level

95%

sides

2-sided

lower limit

-48.43

upper limit

-37.3

Variability estimate

Standard error of the mean

Dispersion value

2.82

Notes
[128] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A10 EZE (Q2W) v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[129]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-28.6

Confidence interval

level

95%

sides

2-sided

lower limit

-33.56

upper limit

-23.65

Variability estimate

Standard error of the mean

Dispersion value

2.51

Notes
[129] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A10 EZE (QM) v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[130]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-30.22

Confidence interval

level

95%

sides

2-sided

lower limit

-35.74

upper limit

-24.7

Variability estimate

Standard error of the mean

Dispersion value

2.8

Notes
[130] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A80 PBO Q2W v A80 EvoMab Q2W

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[131]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-45.1

Confidence interval

level

95%

sides

2-sided

lower limit

-51.66

upper limit

-38.54

Variability estimate

Standard error of the mean

Dispersion value

3.33

Notes
[131] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Placebo QM

Comparison groups

A80 PBO QM v A80 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[132]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-42.43

Confidence interval

level

95%

sides

2-sided

lower limit

-49.01

upper limit

-35.85

Variability estimate

Standard error of the mean

Dispersion value

3.34

Notes
[132] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Ezetimibe (Q2W) v Evolocumab Q2W

Comparison groups

A80 EZE (Q2W) v A80 EvoMab Q2W

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[133]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-30.26

Confidence interval

level

95%

sides

2-sided

lower limit

-36.68

upper limit

-23.84

Variability estimate

Standard error of the mean

Dispersion value

3.26

Notes
[133] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A80 EZE (QM) v A80 EvoMab QM

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[134]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-25.19

Confidence interval

level

95%

sides

2-sided

lower limit

-31.79

upper limit

-18.59

Variability estimate

Standard error of the mean

Dispersion value

3.35

Notes
[134] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R5 PBO Q2W v R5 EvoMab Q2W

Number of subjects included in analysis

171

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[135]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-43.25

Confidence interval

level

95%

sides

2-sided

lower limit

-48.77

upper limit

-37.74

Variability estimate

Standard error of the mean

Dispersion value

2.79

Notes
[135] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab QM vs Placebo QM

Comparison groups

R5 PBO QM v R5 EvoMab QM

Number of subjects included in analysis

172

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[136]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-45.33

Confidence interval

level

95%

sides

2-sided

lower limit

-51.04

upper limit

-39.61

Variability estimate

Standard error of the mean

Dispersion value

2.89

Notes
[136] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R40 PBO Q2W v R40 EvoMab Q2W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[137]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-41.13

Confidence interval

level

95%

sides

2-sided

lower limit

-46.65

upper limit

-35.61

Variability estimate

Standard error of the mean

Dispersion value

2.79

Notes
[137] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab QM vs Placebo QM

Comparison groups

R40 PBO QM v R40 EvoMab QM

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[138]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-34.99

Confidence interval

level

95%

sides

2-sided

lower limit

-41.72

upper limit

-28.25

Variability estimate

Standard error of the mean

Dispersion value

3.41

Notes
[138] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

S40 PBO Q2W v S40 EvoMab Q2W

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[139]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-47.04

Confidence interval

level

95%

sides

2-sided

lower limit

-51.83

upper limit

-42.25

Variability estimate

Standard error of the mean

Dispersion value

2.43

Notes
[139] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab QM vs Placebo QM

Comparison groups

S40 PBO QM v S40 EvoMab QM

Number of subjects included in analysis

170

Analysis specification

Post-hoc

Analysis type

superiority

P-value

< 0.001 ^[140]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-44.6

Confidence interval

level

95%

sides

2-sided

lower limit

-50.67

upper limit

-38.54

Variability estimate

Standard error of the mean

Dispersion value

3.07

Notes
[140] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

Secondary: Mean Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Weeks 10 and 12

Top of page

End point title

Mean Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Weeks 10 and 12

End point description

Efficacy analyses were performed on the full analysis set. Least squares (LS) means are from a repeated measures linear effects model; missing values were not imputed.

End point type

Secondary

End point timeframe

Baseline and Weeks 10 and 12

End point values	A10 PBO Q2W	A10 PBO QM	A10 EZE (Q2W)	A10 EZE (QM)	A10 EvoMab Q2W	A10 EvoMab QM	A80 PBO Q2W	A80 PBO QM	A80 EZE (Q2W)	A80 EZE (QM)	A80 EvoMab Q2W	A80 EvoMab QM	R5 PBO Q2W	R5 PBO QM	R5 EvoMab Q2W	R5 EvoMab QM	R40 PBO Q2W	R40 PBO QM	R40 EvoMab Q2W	R40 EvoMab QM	S40 PBO Q2W	S40 PBO QM	S40 EvoMab Q2W	S40 EvoMab QM
Number of subjects analysed	56	55	56	55	110	110	55	55	56	54	109	110	58	57	113	115	56	55	111	112	56	55	112	115
Units: percent change
least squares mean (standard error)	6.41 ( 2.03 )	0.78 ( 2.29 )	-15.77 ( 2.14 )	-11.47 ( 2.29 )	-53.56 ( 1.48 )	-53.33 ( 1.58 )	4.48 ( 3.04 )	5.79 ( 2.79 )	-15.17 ( 2.99 )	-12.91 ( 2.8 )	-52.43 ( 2.14 )	-56.2 ( 1.98 )	2.82 ( 2.26 )	2.58 ( 2.05 )	-52.46 ( 1.67 )	-56.66 ( 1.43 )	2.17 ( 2.56 )	2.6 ( 2.97 )	-48.47 ( 1.83 )	-54.17 ( 2.04 )	-1 ( 3.12 )	-1.42 ( 4.22 )	-58.76 ( 2.73 )	-57.47 ( 3.55 )

A10: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A10 PBO Q2W v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[141]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-59.97

Confidence interval

level

95%

sides

2-sided

lower limit

-64.91

upper limit

-55.03

Variability estimate

Standard error of the mean

Dispersion value

2.51

Notes
[141] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Placebo QM

Comparison groups

A10 PBO QM v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[142]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-54.11

Confidence interval

level

95%

sides

2-sided

lower limit

-59.57

upper limit

-48.64

Variability estimate

Standard error of the mean

Dispersion value

2.77

Notes
[142] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A10 EZE (Q2W) v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[143]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-37.79

Confidence interval

level

95%

sides

2-sided

lower limit

-42.8

upper limit

-32.77

Variability estimate

Standard error of the mean

Dispersion value

2.54

Notes
[143] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A10 EZE (QM) v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[144]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-41.86

Confidence interval

level

95%

sides

2-sided

lower limit

-47.34

upper limit

-36.67

Variability estimate

Standard error of the mean

Dispersion value

2.78

Notes
[144] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A80 PBO Q2W v A80 EvoMab Q2W

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[145]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-56.9

Confidence interval

level

95%

sides

2-sided

lower limit

-64.22

upper limit

-49.59

Variability estimate

Standard error of the mean

Dispersion value

3.71

Notes
[145] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Placebo QM

Comparison groups

A80 PBO QM v A80 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[146]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-61.99

Confidence interval

level

95%

sides

2-sided

lower limit

-68.68

upper limit

-55.29

Variability estimate

Standard error of the mean

Dispersion value

3.39

Notes
[146] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A80 EZE (Q2W) v A80 EvoMab Q2W

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[147]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-37.26

Confidence interval

level

95%

sides

2-sided

lower limit

-44.48

upper limit

-30.04

Variability estimate

Standard error of the mean

Dispersion value

3.66

Notes
[147] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A80 EZE (QM) v A80 EvoMab QM

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[148]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-43.29

Confidence interval

level

95%

sides

2-sided

lower limit

-50.07

upper limit

-36.51

Variability estimate

Standard error of the mean

Dispersion value

3.44

Notes
[148] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R5 PBO Q2W v R5 EvoMab Q2W

Number of subjects included in analysis

171

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[149]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-55.29

Confidence interval

level

95%

sides

2-sided

lower limit

-60.79

upper limit

-49.79

Variability estimate

Standard error of the mean

Dispersion value

2.78

Notes
[149] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab QM vs Placebo QM

Comparison groups

R5 PBO QM v R5 EvoMab QM

Number of subjects included in analysis

172

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[150]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-59.24

Confidence interval

level

95%

sides

2-sided

lower limit

-64.16

upper limit

-54.32

Variability estimate

Standard error of the mean

Dispersion value

2.49

Notes
[150] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R40 PBO Q2W v R40 EvoMab Q2W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[151]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-50.63

Confidence interval

level

95%

sides

2-sided

lower limit

-56.82

upper limit

-44.45

Variability estimate

Standard error of the mean

Dispersion value

3.13

Notes
[151] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab QM vs Placebo QM

Comparison groups

R40 PBO QM v R40 EvoMab QM

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[152]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-56.78

Confidence interval

level

95%

sides

2-sided

lower limit

-63.91

upper limit

-49.64

Variability estimate

Standard error of the mean

Dispersion value

3.61

Notes
[152] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

S40 PBO Q2W v S40 EvoMab Q2W

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[153]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-57.75

Confidence interval

level

95%

sides

2-sided

lower limit

-62.51

upper limit

-52.99

Variability estimate

Standard error of the mean

Dispersion value

2.41

Notes
[153] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab QM vs Placebo QM

Comparison groups

S40 PBO QM v S40 EvoMab QM

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[154]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-56.06

Confidence interval

level

95%

sides

2-sided

lower limit

-61.85

upper limit

-50.27

Variability estimate

Standard error of the mean

Dispersion value

2.93

Notes
[154] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

Secondary: Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12

Top of page

End point title

Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12

End point description

Efficacy analyses were performed on the full analysis set. Least squares (LS) means are from a repeated measures linear effects model; missing values were not imputed.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	A10 PBO Q2W	A10 PBO QM	A10 EZE (Q2W)	A10 EZE (QM)	A10 EvoMab Q2W	A10 EvoMab QM	A80 PBO Q2W	A80 PBO QM	A80 EZE (Q2W)	A80 EZE (QM)	A80 EvoMab Q2W	A80 EvoMab QM	R5 PBO Q2W	R5 PBO QM	R5 EvoMab Q2W	R5 EvoMab QM	R40 PBO Q2W	R40 PBO QM	R40 EvoMab Q2W	R40 EvoMab QM	S40 PBO Q2W	S40 PBO QM	S40 EvoMab Q2W	S40 EvoMab QM
Number of subjects analysed	56	55	56	55	110	110	55	55	56	54	109	110	58	57	113	115	56	55	111	112	56	55	112	115
Units: percent change
least squares mean (standard error)	6.13 ( 2.2 )	-1.21 ( 2.41 )	-14.51 ( 2.31 )	-12.33 ( 2.41 )	-54.17 ( 1.59 )	-49.65 ( 1.69 )	4.19 ( 3.25 )	6.5 ( 3.18 )	-13.69 ( 3.17 )	-12.19 ( 3.17 )	-53.59 ( 2.26 )	-50.76 ( 2.26 )	1.44 ( 2.3 )	4 ( 2.27 )	-52.97 ( 1.69 )	-52.13 ( 1.6 )	1.64 ( 2.75 )	3.16 ( 3.51 )	-47.53 ( 1.96 )	-45.65 ( 2.39 )	-1.8 ( 3.21 )	-0.52 ( 4.29 )	-59.53 ( 2.77 )	-52.56 ( 3.59 )

A10: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A10 PBO Q2W v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[155]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-60.29

Confidence interval

level

95%

sides

2-sided

lower limit

-65.65

upper limit

-54.94

Variability estimate

Standard error of the mean

Dispersion value

2.71

Notes
[155] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Placebo QM

Comparison groups

A10 PBO QM v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[156]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-48.44

Confidence interval

level

95%

sides

2-sided

lower limit

-54.23

upper limit

-42.65

Variability estimate

Standard error of the mean

Dispersion value

2.94

Notes
[156] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A10 EZE (Q2W) v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[157]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-39.66

Confidence interval

level

95%

sides

2-sided

lower limit

-45.09

upper limit

-34.23

Variability estimate

Standard error of the mean

Dispersion value

2.75

Notes
[157] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A10 EZE (QM) v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[158]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-37.32

Confidence interval

level

95%

sides

2-sided

lower limit

-43.12

upper limit

-31.52

Variability estimate

Standard error of the mean

Dispersion value

2.94

Notes
[158] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A80 PBO Q2W v A80 EvoMab Q2W

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[159]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-57.77

Confidence interval

level

95%

sides

2-sided

lower limit

-65.55

upper limit

-49.99

Variability estimate

Standard error of the mean

Dispersion value

3.95

Notes
[159] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Placebo QM

Comparison groups

A80 PBO QM v A80 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[160]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-57.26

Confidence interval

level

95%

sides

2-sided

lower limit

-64.91

upper limit

-49.6

Variability estimate

Standard error of the mean

Dispersion value

3.88

Notes
[160] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A80 EZE (Q2W) v A80 EvoMab Q2W

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[161]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-39.9

Confidence interval

level

95%

sides

2-sided

lower limit

-47.53

upper limit

-32.26

Variability estimate

Standard error of the mean

Dispersion value

3.87

Notes
[161] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A80 EZE (QM) v A80 EvoMab QM

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[162]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-38.57

Confidence interval

level

95%

sides

2-sided

lower limit

-46.26

upper limit

-30.88

Variability estimate

Standard error of the mean

Dispersion value

3.9

Notes
[162] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R5 PBO Q2W v R5 EvoMab Q2W

Number of subjects included in analysis

171

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[163]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-54.41

Confidence interval

level

95%

sides

2-sided

lower limit

-59.99

upper limit

-48.82

Variability estimate

Standard error of the mean

Dispersion value

2.83

Notes
[163] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab QM vs Placebo QM

Comparison groups

R5 PBO QM v R5 EvoMab QM

Number of subjects included in analysis

172

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001 ^[164]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-56.13

Confidence interval

level

95%

sides

2-sided

lower limit

-61.58

upper limit

-50.68

Variability estimate

Standard error of the mean

Dispersion value

2.76

Notes
[164] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R40 PBO Q2W v R40 EvoMab Q2W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[165]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-49.17

Confidence interval

level

95%

sides

2-sided

lower limit

-55.8

upper limit

-42.53

Variability estimate

Standard error of the mean

Dispersion value

3.36

Notes
[165] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab QM vs Placebo QM

Comparison groups

R40 PBO QM v R40 EvoMab QM

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[166]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-48.81

Confidence interval

level

95%

sides

2-sided

lower limit

-57.21

upper limit

-40.4

Variability estimate

Standard error of the mean

Dispersion value

4.25

Notes
[166] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

S40 PBO Q2W v S40 EvoMab Q2W

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[167]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-57.73

Confidence interval

level

95%

sides

2-sided

lower limit

-62.82

upper limit

-52.65

Variability estimate

Standard error of the mean

Dispersion value

2.57

Notes
[167] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab QM vs Placebo QM

Comparison groups

S40 PBO QM v S40 EvoMab QM

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[168]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-52.04

Confidence interval

level

95%

sides

2-sided

lower limit

-58.1

upper limit

-45.98

Variability estimate

Standard error of the mean

Dispersion value

3.07

Notes
[168] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

Secondary: Mean Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Weeks 10 and 12

Top of page

End point title

Mean Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Weeks 10 and 12

End point description

Calculated LDL-C was determined based on the Friedewald equation. The analysis was performed using the full analysis set.

End point type

Secondary

End point timeframe

Weeks 10 and 12

A10 PBO Q2W

A10 PBO QM

A10 EZE (Q2W)

A10 EZE (QM)

A10 EvoMab Q2W

A10 EvoMab QM

A80 PBO Q2W

A80 PBO QM

A80 EZE (Q2W)

A80 EZE (QM)

A80 EvoMab Q2W

A80 EvoMab QM

R5 PBO Q2W

R5 PBO QM

R5 EvoMab Q2W

R5 EvoMab QM

R40 PBO Q2W

R40 PBO QM

R40 EvoMab Q2W

R40 EvoMab QM

S40 PBO Q2W

S40 PBO QM

S40 EvoMab Q2W

S40 EvoMab QM

Number of subjects analysed

110

109

110

113

115

111

112

115

Units: percentage of participants

number (confidence interval 95%)

5.7 (1.9 to 15.4)

5.6 (1.9 to 15.1)

20 (11.2 to 33)

16.7 (9 to 28.7)

88.1 (80.7 to 92.9)

85.8 (78 to 91.2)

13.7 (6.8 to 25.7)

9.3 (4 to 19.9)

50.9 (38.1 to 63.6)

62.3 (48.8 to 74.1)

94.4 (88.4 to 97.4)

92.5 (85.9 to 96.2)

7 (2.8 to 16.7)

5.3 (1.8 to 14.4)

88.7 (81.2 to 93.4)

89.9 (82.8 to 94.3)

38.9 (27 to 52.2)

28.8 (18.3 to 42.3)

93.5 (87.1 to 96.8)

94.5 (88.6 to 97.5)

1.9 (0.3 to 9.8)

3.9 (1.1 to 13.2)

93.6 (87.3 to 96.9)

88.5 (81.3 to 93.2)

A10: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A10 PBO Q2W v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[169]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

82.4

Confidence interval

level

95%

sides

2-sided

lower limit

70.2

upper limit

88.5

Notes
[169] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Placebo QM

Comparison groups

A10 PBO QM v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[170]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

80.3

Confidence interval

level

95%

sides

2-sided

lower limit

67.9

upper limit

86.8

Notes
[170] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A10 EZE (Q2W) v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[171]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

68.1

Confidence interval

level

95%

sides

2-sided

lower limit

53.1

upper limit

78.1

Notes
[171] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A10 EZE (QM) v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[172]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

69.2

Confidence interval

level

95%

sides

2-sided

lower limit

54.8

upper limit

78.5

Notes
[172] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A80 PBO Q2W v A80 EvoMab Q2W

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[173]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

80.7

Confidence interval

level

95%

sides

2-sided

lower limit

67.3

upper limit

88.3

Notes
[173] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Placebo QM

Comparison groups

A80 PBO QM v A80 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[174]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

83.3

Confidence interval

level

95%

sides

2-sided

lower limit

70.7

upper limit

89.6

Notes
[174] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A80 EZE (Q2W) v A80 EvoMab Q2W

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[175]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

43.5

Confidence interval

level

95%

sides

2-sided

lower limit

29.5

upper limit

56.7

Notes
[175] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A80 EZE (QM) v A80 EvoMab QM

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[176]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

30.3

Confidence interval

level

95%

sides

2-sided

lower limit

16.7

upper limit

44.2

Notes
[176] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R5 PBO Q2W v R5 EvoMab Q2W

Number of subjects included in analysis

171

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[177]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

81.7

Confidence interval

level

95%

sides

2-sided

lower limit

69.5

upper limit

Notes
[177] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab QM vs Placebo QM

Comparison groups

R5 PBO QM v R5 EvoMab QM

Number of subjects included in analysis

172

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[178]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

84.6

Confidence interval

level

95%

sides

2-sided

lower limit

73.1

upper limit

90.2

Notes
[178] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R40 PBO Q2W v R40 EvoMab Q2W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[179]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

54.6

Confidence interval

level

95%

sides

2-sided

lower limit

39.8

upper limit

66.9

Notes
[179] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab QM vs Placebo QM

Comparison groups

R40 PBO QM v R40 EvoMab QM

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[180]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

65.7

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

76.6

Notes
[180] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

S40 PBO Q2W v S40 EvoMab Q2W

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[181]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

91.7

Confidence interval

level

95%

sides

2-sided

lower limit

81.6

upper limit

95.3

Notes
[181] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab QM vs Placebo QM

Comparison groups

S40 PBO QM v S40 EvoMab QM

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[182]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

84.6

Confidence interval

level

95%

sides

2-sided

lower limit

72.8

upper limit

Notes
[182] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

Secondary: Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12

Top of page

End point title

Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12

End point description

Calculated LDL-C was determined based on the Friedewald equation. The analysis was performed using the full analysis set.

End point type

Secondary

End point timeframe

Week 12

A10 PBO Q2W

A10 PBO QM

A10 EZE (Q2W)

A10 EZE (QM)

A10 EvoMab Q2W

A10 EvoMab QM

A80 PBO Q2W

A80 PBO QM

A80 EZE (Q2W)

A80 EZE (QM)

A80 EvoMab Q2W

A80 EvoMab QM

R5 PBO Q2W

R5 PBO QM

R5 EvoMab Q2W

R5 EvoMab QM

R40 PBO Q2W

R40 PBO QM

R40 EvoMab Q2W

R40 EvoMab QM

S40 PBO Q2W

S40 PBO QM

S40 EvoMab Q2W

S40 EvoMab QM

Number of subjects analysed

110

109

110

113

115

111

112

115

Units: percentage of participants

number (confidence interval 95%)

2 (0.3 to 10.3)

5.9 (2 to 15.9)

22.4 (13 to 35.9)

19.2 (10.8 to 31.9)

85.4 (77.4 to 91)

84.2 (75.8 to 90)

13 (6.1 to 25.7)

9.8 (4.3 to 21)

52 (38.5 to 65.2)

55.8 (42.3 to 68.4)

93.1 (86.5 to 96.6)

91 (83.8 to 95.2)

7.7 (3 to 18.2)

5.5 (1.9 to 14.9)

85 (76.7 to 90.7)

86.5 (78.7 to 91.8)

39.6 (27.6 to 53.1)

28 (17.5 to 41.7)

92.3 (85.6 to 96.1)

1.9 (0.3 to 10.1)

6.4 (2.2 to 17.2)

94.4 (88.4 to 97.4)

84.8 (76.7 to 90.4)

A10: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A10 PBO Q2W v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[183]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

83.5

Confidence interval

level

95%

sides

2-sided

lower limit

71.9

upper limit

89.2

Notes
[183] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Placebo QM

Comparison groups

A10 PBO QM v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[184]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

78.3

Confidence interval

level

95%

sides

2-sided

lower limit

65.2

upper limit

85.3

Notes
[184] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A10 EZE (Q2W) v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[185]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

47.3

upper limit

73.9

Notes
[185] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A10 EZE (QM) v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[186]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

64.9

Confidence interval

level

95%

sides

2-sided

lower limit

49.8

upper limit

75.2

Notes
[186] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A80 PBO Q2W v A80 EvoMab Q2W

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[187]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

80.1

Confidence interval

level

95%

sides

2-sided

lower limit

65.8

upper limit

87.9

Notes
[187] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Placebo QM

Comparison groups

A80 PBO QM v A80 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[188]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

81.2

Confidence interval

level

95%

sides

2-sided

lower limit

67.9

upper limit

88.1

Notes
[188] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A80 EZE (Q2W) v A80 EvoMab Q2W

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[189]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

41.1

Confidence interval

level

95%

sides

2-sided

lower limit

26.4

upper limit

55.1

Notes
[189] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A80 EZE (QM) v A80 EvoMab QM

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[190]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

35.2

Confidence interval

level

95%

sides

2-sided

lower limit

20.7

upper limit

49.3

Notes
[190] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R5 PBO Q2W v R5 EvoMab Q2W

Number of subjects included in analysis

171

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[191]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

77.3

Confidence interval

level

95%

sides

2-sided

lower limit

63.9

upper limit

84.7

Notes
[191] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab QM vs Placebo QM

Comparison groups

R5 PBO QM v R5 EvoMab QM

Number of subjects included in analysis

172

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[192]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

81.1

Confidence interval

level

95%

sides

2-sided

lower limit

68.8

upper limit

87.5

Notes
[192] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R40 PBO Q2W v R40 EvoMab Q2W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[193]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

52.7

Confidence interval

level

95%

sides

2-sided

lower limit

37.6

upper limit

65.3

Notes
[193] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab QM vs Placebo QM

Comparison groups

R40 PBO QM v R40 EvoMab QM

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[194]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

64.3

Confidence interval

level

95%

sides

2-sided

lower limit

49.1

upper limit

75.5

Notes
[194] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

S40 PBO Q2W v S40 EvoMab Q2W

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[195]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

92.5

Confidence interval

level

95%

sides

2-sided

lower limit

82.3

upper limit

95.9

Notes
[195] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab QM vs Placebo QM

Comparison groups

S40 PBO QM v S40 EvoMab QM

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[196]

Method

Cochran-Mantel-Haenszel

Parameter type

Treatment Difference

Point estimate

78.4

Confidence interval

level

95%

sides

2-sided

lower limit

64.9

upper limit

85.4

Notes
[196] - Based on Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage). Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

Secondary: Mean Percent Change From Baseline in Lipoprotein(a) at Weeks 10 and 12

Top of page

End point title

Mean Percent Change From Baseline in Lipoprotein(a) at Weeks 10 and 12

End point description

Efficacy analyses were performed on the full analysis set. Least squares (LS) means are from a repeated measures linear effects model; missing values were not imputed.

End point type

Secondary

End point timeframe

Baseline and Weeks 10 and 12

End point values	A10 PBO Q2W	A10 PBO QM	A10 EZE (Q2W)	A10 EZE (QM)	A10 EvoMab Q2W	A10 EvoMab QM	A80 PBO Q2W	A80 PBO QM	A80 EZE (Q2W)	A80 EZE (QM)	A80 EvoMab Q2W	A80 EvoMab QM	R5 PBO Q2W	R5 PBO QM	R5 EvoMab Q2W	R5 EvoMab QM	R40 PBO Q2W	R40 PBO QM	R40 EvoMab Q2W	R40 EvoMab QM	S40 PBO Q2W	S40 PBO QM	S40 EvoMab Q2W	S40 EvoMab QM
Number of subjects analysed	56	55	56	55	110	110	55	55	56	54	109	110	58	57	113	115	56	55	111	112	56	55	112	115
Units: percent change
least squares mean (standard error)	6.07 ( 2.86 )	-0.77 ( 3.28 )	1.44 ( 3.02 )	6.85 ( 3.29 )	-26.01 ( 2.08 )	-22.64 ( 2.27 )	-3.45 ( 2.99 )	1.51 ( 3.35 )	8.05 ( 2.94 )	9.96 ( 3.4 )	-23.97 ( 2.1 )	-27.46 ( 2.39 )	11.41 ( 3 )	3.65 ( 3.56 )	-24.26 ( 2.21 )	-23.16 ( 2.5 )	8.59 ( 2.98 )	6.26 ( 3.59 )	-24.96 ( 2.12 )	-25.93 ( 2.46 )	-10.57 ( 4.49 )	-4.99 ( 5.37 )	-38.64 ( 3.92 )	-32.16 ( 4.5 )

A10: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A10 PBO Q2W v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[197]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-32.08

Confidence interval

level

95%

sides

2-sided

lower limit

-39.06

upper limit

-25.11

Variability estimate

Standard error of the mean

Dispersion value

3.54

Notes
[197] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Placebo QM

Comparison groups

A10 PBO QM v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[198]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-21.86

Confidence interval

level

95%

sides

2-sided

lower limit

-29.7

upper limit

-14.03

Variability estimate

Standard error of the mean

Dispersion value

3.98

Notes
[198] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A10 EZE (Q2W) v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[199]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-27.45

Confidence interval

level

95%

sides

2-sided

lower limit

-34.53

upper limit

-20.38

Variability estimate

Standard error of the mean

Dispersion value

3.59

Notes
[199] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A10 EZE (QM) v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[200]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-29.49

Confidence interval

level

95%

sides

2-sided

lower limit

-37.36

upper limit

-21.62

Variability estimate

Standard error of the mean

Dispersion value

3.99

Notes
[200] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A80 PBO Q2W v A80 EvoMab Q2W

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[201]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-20.52

Confidence interval

level

95%

sides

2-sided

lower limit

-27.71

upper limit

-13.33

Variability estimate

Standard error of the mean

Dispersion value

3.65

Notes
[201] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Placebo QM

Comparison groups

A80 PBO QM v A80 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[202]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-28.96

Confidence interval

level

95%

sides

2-sided

lower limit

-37.01

upper limit

-20.92

Variability estimate

Standard error of the mean

Dispersion value

4.08

Notes
[202] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A80 EZE (Q2W) v A80 EvoMab Q2W

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[203]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-32.02

Confidence interval

level

95%

sides

2-sided

lower limit

-39.11

upper limit

-24.93

Variability estimate

Standard error of the mean

Dispersion value

3.6

Notes
[203] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A80 EZE (QM) v A80 EvoMab QM

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[204]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-37.42

Confidence interval

level

95%

sides

2-sided

lower limit

-45.61

upper limit

-29.23

Variability estimate

Standard error of the mean

Dispersion value

4.15

Notes
[204] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R5 PBO Q2W v R5 EvoMab Q2W

Number of subjects included in analysis

171

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[205]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-35.66

Confidence interval

level

95%

sides

2-sided

lower limit

-42.94

upper limit

-28.38

Variability estimate

Standard error of the mean

Dispersion value

3.69

Notes
[205] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab QM vs Placebo QM

Comparison groups

R5 PBO QM v R5 EvoMab QM

Number of subjects included in analysis

172

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[206]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-26.81

Confidence interval

level

95%

sides

2-sided

lower limit

-35.36

upper limit

-18.27

Variability estimate

Standard error of the mean

Dispersion value

4.33

Notes
[206] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R40 PBO Q2W v R40 EvoMab Q2W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[207]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-33.56

Confidence interval

level

95%

sides

2-sided

lower limit

-40.74

upper limit

-26.37

Variability estimate

Standard error of the mean

Dispersion value

3.64

Notes
[207] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab QM vs Placebo QM

Comparison groups

R40 PBO QM v R40 EvoMab QM

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[208]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-32.19

Confidence interval

level

95%

sides

2-sided

lower limit

-40.8

upper limit

-23.58

Variability estimate

Standard error of the mean

Dispersion value

4.36

Notes
[208] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

S40 PBO Q2W v S40 EvoMab Q2W

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[209]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-28.07

Confidence interval

level

95%

sides

2-sided

lower limit

-34.91

upper limit

-21.23

Variability estimate

Standard error of the mean

Dispersion value

3.46

Notes
[209] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab QM vs Placebo QM

Comparison groups

S40 PBO QM v S40 EvoMab QM

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[210]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-27.16

Confidence interval

level

95%

sides

2-sided

lower limit

-34.59

upper limit

-19.73

Variability estimate

Standard error of the mean

Dispersion value

3.76

Notes
[210] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

Secondary: Percent Change From Baseline in Lipoprotein(a) at Week 12

Top of page

End point title

Percent Change From Baseline in Lipoprotein(a) at Week 12

End point description

Efficacy analyses were performed on the full analysis set. Least squares (LS) means are from a repeated measures linear effects model; missing values were not imputed.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	A10 PBO Q2W	A10 PBO QM	A10 EZE (Q2W)	A10 EZE (QM)	A10 EvoMab Q2W	A10 EvoMab QM	A80 PBO Q2W	A80 PBO QM	A80 EZE (Q2W)	A80 EZE (QM)	A80 EvoMab Q2W	A80 EvoMab QM	R5 PBO Q2W	R5 PBO QM	R5 EvoMab Q2W	R5 EvoMab QM	R40 PBO Q2W	R40 PBO QM	R40 EvoMab Q2W	R40 EvoMab QM	S40 PBO Q2W	S40 PBO QM	S40 EvoMab Q2W	S40 EvoMab QM
Number of subjects analysed	56	55	56	55	110	110	55	55	56	54	109	110	58	57	113	115	56	55	111	112	56	55	112	115
Units: percent change
least squares mean (standard error)	7.34 ( 3.13 )	-0.43 ( 3.38 )	3.29 ( 3.28 )	7.18 ( 3.38 )	-25.87 ( 2.26 )	-20.25 ( 2.36 )	-2.23 ( 3.35 )	3.41 ( 3.54 )	8.01 ( 3.26 )	10.2 ( 3.57 )	-24.61 ( 2.31 )	-24.68 ( 2.53 )	11.4 ( 3.37 )	4.49 ( 3.68 )	-25.09 ( 2.47 )	-20.85 ( 2.59 )	10.38 ( 3.09 )	10.21 ( 4.36 )	-26.11 ( 2.21 )	-21.97 ( 2.97 )	-6.81 ( 4.57 )	-1.06 ( 5.67 )	-38.06 ( 3.96 )	-29.23 ( 4.68 )

A10: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A10 PBO Q2W v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[211]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-33.2

Confidence interval

level

95%

sides

2-sided

lower limit

-40.81

upper limit

-25.6

Variability estimate

Standard error of the mean

Dispersion value

3.86

Notes
[211] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Placebo QM

Comparison groups

A10 PBO QM v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[212]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-19.82

Confidence interval

level

95%

sides

2-sided

lower limit

-27.92

upper limit

-11.72

Variability estimate

Standard error of the mean

Dispersion value

4.11

Notes
[212] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A10 EZE (Q2W) v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[213]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-29.16

Confidence interval

level

95%

sides

2-sided

lower limit

-36.87

upper limit

-21.44

Variability estimate

Standard error of the mean

Dispersion value

3.91

Notes
[213] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A10 EZE (QM) v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[214]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-27.44

Confidence interval

level

95%

sides

2-sided

lower limit

-35.56

upper limit

-19.32

Variability estimate

Standard error of the mean

Dispersion value

4.12

Notes
[214] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A80 PBO Q2W v A80 EvoMab Q2W

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[215]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-22.38

Confidence interval

level

95%

sides

2-sided

lower limit

-30.39

upper limit

-14.36

Variability estimate

Standard error of the mean

Dispersion value

4.07

Notes
[215] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Placebo QM

Comparison groups

A80 PBO QM v A80 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[216]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-28.1

Confidence interval

level

95%

sides

2-sided

lower limit

-36.62

upper limit

-19.58

Variability estimate

Standard error of the mean

Dispersion value

4.32

Notes
[216] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A80 EZE (Q2W) v A80 EvoMab Q2W

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[217]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-32.62

Confidence interval

level

95%

sides

2-sided

lower limit

-40.46

upper limit

-24.78

Variability estimate

Standard error of the mean

Dispersion value

3.98

Notes
[217] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A80 EZE (QM) v A80 EvoMab QM

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[218]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-34.88

Confidence interval

level

95%

sides

2-sided

lower limit

-43.52

upper limit

-26.25

Variability estimate

Standard error of the mean

Dispersion value

4.38

Notes
[218] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R5 PBO Q2W v R5 EvoMab Q2W

Number of subjects included in analysis

171

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[219]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-36.5

Confidence interval

level

95%

sides

2-sided

lower limit

-44.69

upper limit

-28.3

Variability estimate

Standard error of the mean

Dispersion value

4.15

Notes
[219] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab QM vs Placebo QM

Comparison groups

R5 PBO QM v R5 EvoMab QM

Number of subjects included in analysis

172

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[220]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-25.34

Confidence interval

level

95%

sides

2-sided

lower limit

-34.19

upper limit

-16.49

Variability estimate

Standard error of the mean

Dispersion value

4.48

Notes
[220] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R40 PBO Q2W v R40 EvoMab Q2W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[221]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-36.48

Confidence interval

level

95%

sides

2-sided

lower limit

-43.95

upper limit

-29.02

Variability estimate

Standard error of the mean

Dispersion value

3.78

Notes
[221] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab QM vs Placebo QM

Comparison groups

R40 PBO QM v R40 EvoMab QM

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[222]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-32.17

Confidence interval

level

95%

sides

2-sided

lower limit

-42.61

upper limit

-21.74

Variability estimate

Standard error of the mean

Dispersion value

5.28

Notes
[222] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

S40 PBO Q2W v S40 EvoMab Q2W

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[223]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-31.25

Confidence interval

level

95%

sides

2-sided

lower limit

-38.4

upper limit

-24.1

Variability estimate

Standard error of the mean

Dispersion value

3.62

Notes
[223] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab QM vs Placebo QM

Comparison groups

S40 PBO QM v S40 EvoMab QM

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[224]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-28.17

Confidence interval

level

95%

sides

2-sided

lower limit

-36.79

upper limit

-19.55

Variability estimate

Standard error of the mean

Dispersion value

4.36

Notes
[224] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

Secondary: Mean Percent Change From Baseline in Triglycerides at Weeks 10 and 12

Top of page

End point title

Mean Percent Change From Baseline in Triglycerides at Weeks 10 and 12

End point description

Efficacy analyses were performed on the full analysis set. Least squares (LS) means are from a repeated measures linear effects model; missing values were not imputed.

End point type

Secondary

End point timeframe

Baseline and Weeks 10 and 12

End point values	A10 PBO Q2W	A10 PBO QM	A10 EZE (Q2W)	A10 EZE (QM)	A10 EvoMab Q2W	A10 EvoMab QM	A80 PBO Q2W	A80 PBO QM	A80 EZE (Q2W)	A80 EZE (QM)	A80 EvoMab Q2W	A80 EvoMab QM	R5 PBO Q2W	R5 PBO QM	R5 EvoMab Q2W	R5 EvoMab QM	R40 PBO Q2W	R40 PBO QM	R40 EvoMab Q2W	R40 EvoMab QM	S40 PBO Q2W	S40 PBO QM	S40 EvoMab Q2W	S40 EvoMab QM
Number of subjects analysed	56	55	56	55	110	110	55	55	56	54	109	110	58	57	113	115	56	55	111	112	56	55	112	115
Units: percent change
least squares mean (standard error)	6.49 ( 3.94 )	9.17 ( 4.41 )	-3.16 ( 4.1 )	1.57 ( 4.35 )	-5.61 ( 2.81 )	-13.38 ( 3.08 )	6.16 ( 4.02 )	8.05 ( 4.35 )	-8.1 ( 3.92 )	-4.86 ( 4.39 )	-9.27 ( 2.8 )	-6.36 ( 3.11 )	12.43 ( 4.19 )	12.26 ( 4.67 )	-10.28 ( 3.04 )	-7.26 ( 3.29 )	8.44 ( 3.76 )	10.75 ( 3.98 )	-9.15 ( 2.7 )	-15.43 ( 2.77 )	9.29 ( 6.97 )	13.78 ( 7.44 )	-11.67 ( 5.97 )	-15.93 ( 6.15 )

A10: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A10 PBO Q2W v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2 ^[225]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-12.1

Confidence interval

level

95%

sides

2-sided

lower limit

-21.63

upper limit

-2.58

Variability estimate

Standard error of the mean

Dispersion value

4.83

Notes
[225] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Placebo QM

Comparison groups

A10 PBO QM v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[226]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-22.55

Confidence interval

level

95%

sides

2-sided

lower limit

-33.13

upper limit

-11.97

Variability estimate

Standard error of the mean

Dispersion value

5.36

Notes
[226] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A10 EZE (Q2W) v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 1 ^[227]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-2.45

Confidence interval

level

95%

sides

2-sided

lower limit

-12.09

upper limit

7.19

Variability estimate

Standard error of the mean

Dispersion value

4.89

Notes
[227] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A10 EZE (QM) v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.053 ^[228]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-14.95

Confidence interval

level

95%

sides

2-sided

lower limit

-25.46

upper limit

-4.44

Variability estimate

Standard error of the mean

Dispersion value

5.33

Notes
[228] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A80 PBO Q2W v A80 EvoMab Q2W

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.073 ^[229]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-15.43

Confidence interval

level

95%

sides

2-sided

lower limit

-25.06

upper limit

-5.79

Variability estimate

Standard error of the mean

Dispersion value

4.89

Notes
[229] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Placebo QM

Comparison groups

A80 PBO QM v A80 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.027 ^[230]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-14.41

Confidence interval

level

95%

sides

2-sided

lower limit

-24.9

upper limit

-3.92

Variability estimate

Standard error of the mean

Dispersion value

5.32

Notes
[230] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A80 EZE (Q2W) v A80 EvoMab Q2W

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 1 ^[231]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-1.17

Confidence interval

level

95%

sides

2-sided

lower limit

-10.63

upper limit

8.3

Variability estimate

Standard error of the mean

Dispersion value

4.8

Notes
[231] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A80 EZE (QM) v A80 EvoMab QM

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.63 ^[232]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-1.51

Confidence interval

level

95%

sides

2-sided

lower limit

-12.12

upper limit

9.11

Variability estimate

Standard error of the mean

Dispersion value

5.38

Notes
[232] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R5 PBO Q2W v R5 EvoMab Q2W

Number of subjects included in analysis

171

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[233]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-22.72

Confidence interval

level

95%

sides

2-sided

lower limit

-32.9

upper limit

-12.54

Variability estimate

Standard error of the mean

Dispersion value

5.15

Notes
[233] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab QM vs Placebo QM

Comparison groups

R5 PBO QM v R5 EvoMab QM

Number of subjects included in analysis

172

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.007 ^[234]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-19.52

Confidence interval

level

95%

sides

2-sided

lower limit

-30.76

upper limit

-8.28

Variability estimate

Standard error of the mean

Dispersion value

5.69

Notes
[234] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R40 PBO Q2W v R40 EvoMab Q2W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[235]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-17.59

Confidence interval

level

95%

sides

2-sided

lower limit

-26.71

upper limit

-8.46

Variability estimate

Standard error of the mean

Dispersion value

4.62

Notes
[235] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab QM vs Placebo QM

Comparison groups

R40 PBO QM v R40 EvoMab QM

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[236]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-26.18

Confidence interval

level

95%

sides

2-sided

lower limit

-35.76

upper limit

-16.59

Variability estimate

Standard error of the mean

Dispersion value

4.85

Notes
[236] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

S40 PBO Q2W v S40 EvoMab Q2W

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[237]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-20.97

Confidence interval

level

95%

sides

2-sided

lower limit

-32.38

upper limit

-9.55

Variability estimate

Standard error of the mean

Dispersion value

5.78

Notes
[237] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab QM vs Placebo QM

Comparison groups

S40 PBO QM v S40 EvoMab QM

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[238]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-29.71

Confidence interval

level

95%

sides

2-sided

lower limit

-40.84

upper limit

-18.57

Variability estimate

Standard error of the mean

Dispersion value

5.64

Notes
[238] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

Secondary: Percent Change From Baseline in Triglycerides at Week 12

Top of page

End point title

Percent Change From Baseline in Triglycerides at Week 12

End point description

Efficacy analyses were performed on the full analysis set. Least squares (LS) means are from a repeated measures linear effects model; missing values were not imputed.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	A10 PBO Q2W	A10 PBO QM	A10 EZE (Q2W)	A10 EZE (QM)	A10 EvoMab Q2W	A10 EvoMab QM	A80 PBO Q2W	A80 PBO QM	A80 EZE (Q2W)	A80 EZE (QM)	A80 EvoMab Q2W	A80 EvoMab QM	R5 PBO Q2W	R5 PBO QM	R5 EvoMab Q2W	R5 EvoMab QM	R40 PBO Q2W	R40 PBO QM	R40 EvoMab Q2W	R40 EvoMab QM	S40 PBO Q2W	S40 PBO QM	S40 EvoMab Q2W	S40 EvoMab QM
Number of subjects analysed	56	55	56	55	110	110	55	55	56	54	109	110	58	57	113	115	56	55	111	112	56	55	112	115
Units: percent change
least squares mean (standard error)	8.27 ( 5.23 )	14.35 ( 5.92 )	-0.43 ( 5.39 )	4.88 ( 5.84 )	-3.79 ( 3.72 )	-13.26 ( 4.17 )	6.65 ( 4.45 )	8.22 ( 5.22 )	-7.4 ( 4.32 )	-3.11 ( 5.23 )	-10.07 ( 3.05 )	-1.1 ( 3.74 )	13.57 ( 5.76 )	12.96 ( 5.32 )	-4.46 ( 4.16 )	-6.88 ( 3.8 )	10.97 ( 4.66 )	10 ( 4.38 )	-5.58 ( 3.34 )	-10.51 ( 3.04 )	8.07 ( 6.88 )	16.72 ( 7.88 )	-13.71 ( 5.91 )	-14.65 ( 6.39 )

A10: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A10 PBO Q2W v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2 ^[239]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-12.06

Confidence interval

level

95%

sides

2-sided

lower limit

-24.69

upper limit

0.57

Variability estimate

Standard error of the mean

Dispersion value

6.41

Notes
[239] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Placebo QM

Comparison groups

A10 PBO QM v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[240]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-27.6

Confidence interval

level

95%

sides

2-sided

lower limit

-41.86

upper limit

-13.35

Variability estimate

Standard error of the mean

Dispersion value

7.23

Notes
[240] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A10 EZE (Q2W) v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 1 ^[241]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-3.37

Confidence interval

level

95%

sides

2-sided

lower limit

-16.16

upper limit

9.43

Variability estimate

Standard error of the mean

Dispersion value

6.49

Notes
[241] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A10 EZE (QM) v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.053 ^[242]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-18.13

Confidence interval

level

95%

sides

2-sided

lower limit

-32.28

upper limit

-3.99

Variability estimate

Standard error of the mean

Dispersion value

7.18

Notes
[242] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A80 PBO Q2W v A80 EvoMab Q2W

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.073 ^[243]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-16.72

Confidence interval

level

95%

sides

2-sided

lower limit

-27.34

upper limit

-6.1

Variability estimate

Standard error of the mean

Dispersion value

5.39

Notes
[243] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Placebo QM

Comparison groups

A80 PBO QM v A80 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.027 ^[244]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-9.31

Confidence interval

level

95%

sides

2-sided

lower limit

-21.92

upper limit

3.29

Variability estimate

Standard error of the mean

Dispersion value

6.39

Notes
[244] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A80 EZE (Q2W) v A80 EvoMab Q2W

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 1 ^[245]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-2.67

Confidence interval

level

95%

sides

2-sided

lower limit

-13.05

upper limit

7.72

Variability estimate

Standard error of the mean

Dispersion value

5.27

Notes
[245] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A80 EZE (QM) v A80 EvoMab QM

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.63 ^[246]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

2.02

Confidence interval

level

95%

sides

2-sided

lower limit

-10.66

upper limit

14.69

Variability estimate

Standard error of the mean

Dispersion value

6.43

Notes
[246] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R5 PBO Q2W v R5 EvoMab Q2W

Number of subjects included in analysis

171

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[247]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-18.03

Confidence interval

level

95%

sides

2-sided

lower limit

-32.03

upper limit

-4.04

Variability estimate

Standard error of the mean

Dispersion value

7.08

Notes
[247] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab QM vs Placebo QM

Comparison groups

R5 PBO QM v R5 EvoMab QM

Number of subjects included in analysis

172

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.007 ^[248]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-19.83

Confidence interval

level

95%

sides

2-sided

lower limit

-32.71

upper limit

-6.96

Variability estimate

Standard error of the mean

Dispersion value

6.52

Notes
[248] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R40 PBO Q2W v R40 EvoMab Q2W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[249]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-16.55

Confidence interval

level

95%

sides

2-sided

lower limit

-27.84

upper limit

-5.26

Variability estimate

Standard error of the mean

Dispersion value

5.71

Notes
[249] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab QM vs Placebo QM

Comparison groups

R40 PBO QM v R40 EvoMab QM

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[250]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-20.51

Confidence interval

level

95%

sides

2-sided

lower limit

-31.04

upper limit

-9.98

Variability estimate

Standard error of the mean

Dispersion value

5.33

Notes
[250] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

S40 PBO Q2W v S40 EvoMab Q2W

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[251]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-21.78

Confidence interval

level

95%

sides

2-sided

lower limit

-32.88

upper limit

-10.68

Variability estimate

Standard error of the mean

Dispersion value

5.62

Notes
[251] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab QM vs Placebo QM

Comparison groups

S40 PBO QM v S40 EvoMab QM

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[252]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-31.36

Confidence interval

level

95%

sides

2-sided

lower limit

-44.1

upper limit

-18.62

Variability estimate

Standard error of the mean

Dispersion value

6.45

Notes
[252] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

Secondary: Mean Percent Change From Baseline in Very Low-Density Cholesterol (VLDL-C) at Weeks 10 and 12

Top of page

End point title

Mean Percent Change From Baseline in Very Low-Density Cholesterol (VLDL-C) at Weeks 10 and 12

End point description

Efficacy analyses were performed on the full analysis set. Least squares (LS) means are from a repeated measures linear effects model; missing values were not imputed.

End point type

Secondary

End point timeframe

Baseline and Weeks 10 and 12

End point values	A10 PBO Q2W	A10 PBO QM	A10 EZE (Q2W)	A10 EZE (QM)	A10 EvoMab Q2W	A10 EvoMab QM	A80 PBO Q2W	A80 PBO QM	A80 EZE (Q2W)	A80 EZE (QM)	A80 EvoMab Q2W	A80 EvoMab QM	R5 PBO Q2W	R5 PBO QM	R5 EvoMab Q2W	R5 EvoMab QM	R40 PBO Q2W	R40 PBO QM	R40 EvoMab Q2W	R40 EvoMab QM	S40 PBO Q2W	S40 PBO QM	S40 EvoMab Q2W	S40 EvoMab QM
Number of subjects analysed	56	55	56	55	110	110	55	55	56	54	109	110	58	57	113	115	56	55	111	112	56	55	112	115
Units: percent change
least squares mean (standard error)	6.51 ( 3.56 )	9.53 ( 4.45 )	-5.35 ( 3.74 )	1.77 ( 4.41 )	-6.85 ( 2.56 )	-11.77 ( 3.11 )	6.24 ( 4.03 )	8.31 ( 4.26 )	-8.52 ( 3.93 )	-6.13 ( 4.31 )	-8.96 ( 2.82 )	-6.38 ( 3.05 )	12.86 ( 3.95 )	12.54 ( 4.58 )	-12.22 ( 2.86 )	-7.25 ( 3.23 )	7.06 ( 3.76 )	8.13 ( 3.72 )	-9.09 ( 2.71 )	-15.05 ( 2.58 )	8.64 ( 6.01 )	16.37 ( 7.15 )	-14.57 ( 5.17 )	-16.5 ( 5.87 )

A10: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A10 PBO Q2W v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.088 ^[253]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-13.36

Confidence interval

level

95%

sides

2-sided

lower limit

-21.99

upper limit

-4.74

Variability estimate

Standard error of the mean

Dispersion value

4.38

Notes
[253] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Placebo QM

Comparison groups

A10 PBO QM v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.005 ^[254]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-21.31

Confidence interval

level

95%

sides

2-sided

lower limit

-31.98

upper limit

-10.64

Variability estimate

Standard error of the mean

Dispersion value

5.41

Notes
[254] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A10 EZE (Q2W) v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 1 ^[255]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-1.5

Confidence interval

level

95%

sides

2-sided

lower limit

-10.27

upper limit

7.27

Variability estimate

Standard error of the mean

Dispersion value

4.45

Notes
[255] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A10 EZE (QM) v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.056 ^[256]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-13.54

Confidence interval

level

95%

sides

2-sided

lower limit

-24.17

upper limit

-2.91

Variability estimate

Standard error of the mean

Dispersion value

5.39

Notes
[256] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A80 PBO Q2W v A80 EvoMab Q2W

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.073 ^[257]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-15.21

Confidence interval

level

95%

sides

2-sided

lower limit

-24.88

upper limit

-5.54

Variability estimate

Standard error of the mean

Dispersion value

4.91

Notes
[257] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Placebo QM

Comparison groups

A80 PBO QM v A80 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.027 ^[258]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-14.69

Confidence interval

level

95%

sides

2-sided

lower limit

-24.97

upper limit

-4.42

Variability estimate

Standard error of the mean

Dispersion value

5.21

Notes
[258] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A80 EZE (Q2W) v A80 EvoMab Q2W

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 1 ^[259]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-0.44

Confidence interval

level

95%

sides

2-sided

lower limit

-9.94

upper limit

9.05

Variability estimate

Standard error of the mean

Dispersion value

4.82

Notes
[259] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A80 EZE (QM) v A80 EvoMab QM

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.62 ^[260]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-0.25

Confidence interval

level

95%

sides

2-sided

lower limit

-10.66

upper limit

10.16

Variability estimate

Standard error of the mean

Dispersion value

5.28

Notes
[260] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R5 PBO Q2W v R5 EvoMab Q2W

Number of subjects included in analysis

171

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[261]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-25.07

Confidence interval

level

95%

sides

2-sided

lower limit

-34.64

upper limit

-15.5

Variability estimate

Standard error of the mean

Dispersion value

4.85

Notes
[261] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab QM vs Placebo QM

Comparison groups

R5 PBO QM v R5 EvoMab QM

Number of subjects included in analysis

172

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.007 ^[262]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-19.79

Confidence interval

level

95%

sides

2-sided

lower limit

-30.81

upper limit

-8.77

Variability estimate

Standard error of the mean

Dispersion value

5.58

Notes
[262] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R40 PBO Q2W v R40 EvoMab Q2W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.005 ^[263]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-16.15

Confidence interval

level

95%

sides

2-sided

lower limit

-25.27

upper limit

-7.03

Variability estimate

Standard error of the mean

Dispersion value

4.61

Notes
[263] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab QM vs Placebo QM

Comparison groups

R40 PBO QM v R40 EvoMab QM

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[264]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-23.18

Confidence interval

level

95%

sides

2-sided

lower limit

-32.11

upper limit

-14.25

Variability estimate

Standard error of the mean

Dispersion value

4.52

Notes
[264] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

S40 PBO Q2W v S40 EvoMab Q2W

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[265]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-23.21

Confidence interval

level

95%

sides

2-sided

lower limit

-33

upper limit

-13.43

Variability estimate

Standard error of the mean

Dispersion value

4.95

Notes
[265] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab QM vs Placebo QM

Comparison groups

S40 PBO QM v S40 EvoMab QM

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[266]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-32.87

Confidence interval

level

95%

sides

2-sided

lower limit

-43.6

upper limit

-22.14

Variability estimate

Standard error of the mean

Dispersion value

5.43

Notes
[266] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

Secondary: Percent Change From Baseline in VLDL-C at Week 12

Top of page

End point title

Percent Change From Baseline in VLDL-C at Week 12

End point description

Efficacy analyses were performed on the full analysis set. Least squares (LS) means are from a repeated measures linear effects model; missing values were not imputed.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	A10 PBO Q2W	A10 PBO QM	A10 EZE (Q2W)	A10 EZE (QM)	A10 EvoMab Q2W	A10 EvoMab QM	A80 PBO Q2W	A80 PBO QM	A80 EZE (Q2W)	A80 EZE (QM)	A80 EvoMab Q2W	A80 EvoMab QM	R5 PBO Q2W	R5 PBO QM	R5 EvoMab Q2W	R5 EvoMab QM	R40 PBO Q2W	R40 PBO QM	R40 EvoMab Q2W	R40 EvoMab QM	S40 PBO Q2W	S40 PBO QM	S40 EvoMab Q2W	S40 EvoMab QM
Number of subjects analysed	56	55	56	55	110	110	55	55	56	54	109	110	58	57	113	115	56	55	111	112	56	55	112	115
Units: percent change
least squares mean (standard error)	8.32 ( 4 )	14.74 ( 5.91 )	-4.61 ( 4.19 )	3.45 ( 5.89 )	-6.16 ( 2.88 )	-11.73 ( 4.16 )	6.73 ( 4.45 )	8.54 ( 5 )	-7.92 ( 4.32 )	-6 ( 5.04 )	-9.69 ( 3.05 )	-1.06 ( 3.58 )	13.79 ( 5.05 )	12.47 ( 5.31 )	-8.2 ( 3.64 )	-6.28 ( 3.78 )	10.09 ( 4.65 )	8.59 ( 4.37 )	-6.1 ( 3.33 )	-9.95 ( 3.03 )	7.63 ( 6.26 )	20.97 ( 7.53 )	-14.83 ( 5.3 )	-15.86 ( 6.09 )

A10: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A10 PBO Q2W v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.088 ^[267]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-14.47

Confidence interval

level

95%

sides

2-sided

lower limit

-24.16

upper limit

-4.78

Variability estimate

Standard error of the mean

Dispersion value

4.92

Notes
[267] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Placebo QM

Comparison groups

A10 PBO QM v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.005 ^[268]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-26.47

Confidence interval

level

95%

sides

2-sided

lower limit

-40.71

upper limit

-12.24

Variability estimate

Standard error of the mean

Dispersion value

7.22

Notes
[268] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A10 EZE (Q2W) v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 1 ^[269]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-1.54

Confidence interval

level

95%

sides

2-sided

lower limit

-11.41

upper limit

8.32

Variability estimate

Standard error of the mean

Dispersion value

Notes
[269] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A10 EZE (QM) v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.056 ^[270]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-15.19

Confidence interval

level

95%

sides

2-sided

lower limit

-29.4

upper limit

-0.97

Variability estimate

Standard error of the mean

Dispersion value

7.21

Notes
[270] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A80 PBO Q2W v A80 EvoMab Q2W

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.073 ^[271]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-16.42

Confidence interval

level

95%

sides

2-sided

lower limit

-27.05

upper limit

-5.8

Variability estimate

Standard error of the mean

Dispersion value

5.39

Notes
[271] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Placebo QM

Comparison groups

A80 PBO QM v A80 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.027 ^[272]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-9.6

Confidence interval

level

95%

sides

2-sided

lower limit

-21.68

upper limit

2.48

Variability estimate

Standard error of the mean

Dispersion value

6.13

Notes
[272] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A80 EZE (Q2W) v A80 EvoMab Q2W

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 1 ^[273]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-1.78

Confidence interval

level

95%

sides

2-sided

lower limit

-12.16

upper limit

8.61

Variability estimate

Standard error of the mean

Dispersion value

5.27

Notes
[273] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A80 EZE (QM) v A80 EvoMab QM

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.62 ^[274]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

4.94

Confidence interval

level

95%

sides

2-sided

lower limit

-7.25

upper limit

17.14

Variability estimate

Standard error of the mean

Dispersion value

6.18

Notes
[274] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R5 PBO Q2W v R5 EvoMab Q2W

Number of subjects included in analysis

171

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[275]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-21.98

Confidence interval

level

95%

sides

2-sided

lower limit

-34.24

upper limit

-9.73

Variability estimate

Standard error of the mean

Dispersion value

6.2

Notes
[275] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab QM vs Placebo QM

Comparison groups

R5 PBO QM v R5 EvoMab QM

Number of subjects included in analysis

172

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.007 ^[276]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-18.75

Confidence interval

level

95%

sides

2-sided

lower limit

-31.6

upper limit

-5.9

Variability estimate

Standard error of the mean

Dispersion value

6.5

Notes
[276] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R40 PBO Q2W v R40 EvoMab Q2W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.005 ^[277]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-16.19

Confidence interval

level

95%

sides

2-sided

lower limit

-27.46

upper limit

-4.92

Variability estimate

Standard error of the mean

Dispersion value

5.7

Notes
[277] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab QM vs Placebo QM

Comparison groups

R40 PBO QM v R40 EvoMab QM

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[278]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-18.54

Confidence interval

level

95%

sides

2-sided

lower limit

-29.04

upper limit

-8.05

Variability estimate

Standard error of the mean

Dispersion value

5.31

Notes
[278] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

S40 PBO Q2W v S40 EvoMab Q2W

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[279]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-22.45

Confidence interval

level

95%

sides

2-sided

lower limit

-33.09

upper limit

-11.81

Variability estimate

Standard error of the mean

Dispersion value

5.39

Notes
[279] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab QM vs Placebo QM

Comparison groups

S40 PBO QM v S40 EvoMab QM

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[280]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

-36.83

Confidence interval

level

95%

sides

2-sided

lower limit

-48.96

upper limit

-24.7

Variability estimate

Standard error of the mean

Dispersion value

6.14

Notes
[280] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

Secondary: Mean percent Change From Baseline in HDL-C at Weeks 10 and 12

Top of page

End point title

Mean percent Change From Baseline in HDL-C at Weeks 10 and 12

End point description

Efficacy analyses were performed on the full analysis set. Least squares (LS) means are from a repeated measures linear effects model; missing values were not imputed.

End point type

Secondary

End point timeframe

Baseline and Weeks 10 and 12

End point values	A10 PBO Q2W	A10 PBO QM	A10 EZE (Q2W)	A10 EZE (QM)	A10 EvoMab Q2W	A10 EvoMab QM	A80 PBO Q2W	A80 PBO QM	A80 EZE (Q2W)	A80 EZE (QM)	A80 EvoMab Q2W	A80 EvoMab QM	R5 PBO Q2W	R5 PBO QM	R5 EvoMab Q2W	R5 EvoMab QM	R40 PBO Q2W	R40 PBO QM	R40 EvoMab Q2W	R40 EvoMab QM	S40 PBO Q2W	S40 PBO QM	S40 EvoMab Q2W	S40 EvoMab QM
Number of subjects analysed	56	55	56	55	110	110	55	55	56	54	109	110	58	57	113	115	56	55	111	112	56	55	112	115
Units: percent change
least squares mean (standard error)	-0.99 ( 1.5 )	-0.45 ( 1.94 )	-1.13 ( 1.56 )	-0.92 ( 1.92 )	5.54 ( 1.07 )	7.66 ( 1.37 )	4.48 ( 1.73 )	-1.37 ( 1.85 )	0.86 ( 1.68 )	-0.59 ( 1.86 )	8.44 ( 1.2 )	7.76 ( 1.31 )	0.87 ( 1.52 )	-0.94 ( 2.55 )	6.23 ( 1.1 )	7.72 ( 1.8 )	-0.6 ( 1.56 )	-0.4 ( 1.81 )	4.86 ( 1.12 )	6.35 ( 1.26 )	0.13 ( 2.75 )	-2.14 ( 2.72 )	10.35 ( 2.26 )	6.71 ( 2.25 )

A10: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A10 PBO Q2W v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.034 ^[281]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

6.53

Confidence interval

level

95%

sides

2-sided

lower limit

2.91

upper limit

10.15

Variability estimate

Standard error of the mean

Dispersion value

1.84

Notes
[281] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Placebo QM

Comparison groups

A10 PBO QM v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.017 ^[282]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

8.11

Confidence interval

level

95%

sides

2-sided

lower limit

3.43

upper limit

12.79

Variability estimate

Standard error of the mean

Dispersion value

2.37

Notes
[282] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A10 EZE (Q2W) v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[283]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

6.67

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

10.34

Variability estimate

Standard error of the mean

Dispersion value

1.86

Notes
[283] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A10 EZE (QM) v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006 ^[284]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

8.57

Confidence interval

level

95%

sides

2-sided

lower limit

3.93

upper limit

13.22

Variability estimate

Standard error of the mean

Dispersion value

2.36

Notes
[284] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A80 PBO Q2W v A80 EvoMab Q2W

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.85 ^[285]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

3.95

Confidence interval

level

95%

sides

2-sided

lower limit

-0.19

upper limit

8.09

Variability estimate

Standard error of the mean

Dispersion value

2.1

Notes
[285] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Placebo QM

Comparison groups

A80 PBO QM v A80 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[286]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

9.13

Confidence interval

level

95%

sides

2-sided

lower limit

4.68

upper limit

13.58

Variability estimate

Standard error of the mean

Dispersion value

2.26

Notes
[286] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A80 EZE (Q2W) v A80 EvoMab Q2W

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[287]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

7.57

Confidence interval

level

95%

sides

2-sided

lower limit

3.51

upper limit

11.64

Variability estimate

Standard error of the mean

Dispersion value

2.06

Notes
[287] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A80 EZE (QM) v A80 EvoMab QM

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[288]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

8.35

Confidence interval

level

95%

sides

2-sided

lower limit

3.86

upper limit

12.84

Variability estimate

Standard error of the mean

Dispersion value

2.28

Notes
[288] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R5 PBO Q2W v R5 EvoMab Q2W

Number of subjects included in analysis

171

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[289]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

5.36

Confidence interval

level

95%

sides

2-sided

lower limit

1.68

upper limit

9.04

Variability estimate

Standard error of the mean

Dispersion value

1.87

Notes
[289] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab QM vs Placebo QM

Comparison groups

R5 PBO QM v R5 EvoMab QM

Number of subjects included in analysis

172

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.01 ^[290]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

8.66

Confidence interval

level

95%

sides

2-sided

lower limit

2.51

upper limit

14.8

Variability estimate

Standard error of the mean

Dispersion value

3.11

Notes
[290] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R40 PBO Q2W v R40 EvoMab Q2W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.013 ^[291]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

5.46

Confidence interval

level

95%

sides

2-sided

lower limit

1.69

upper limit

9.23

Variability estimate

Standard error of the mean

Dispersion value

1.91

Notes
[291] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab QM vs Placebo QM

Comparison groups

R40 PBO QM v R40 EvoMab QM

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[292]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

6.75

Confidence interval

level

95%

sides

2-sided

lower limit

2.4

upper limit

11.1

Variability estimate

Standard error of the mean

Dispersion value

2.2

Notes
[292] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

S40 PBO Q2W v S40 EvoMab Q2W

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[293]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

10.23

Confidence interval

level

95%

sides

2-sided

lower limit

5.13

upper limit

15.32

Variability estimate

Standard error of the mean

Dispersion value

2.58

Notes
[293] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab QM vs Placebo QM

Comparison groups

S40 PBO QM v S40 EvoMab QM

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[294]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

8.85

Confidence interval

level

95%

sides

2-sided

lower limit

4.73

upper limit

12.97

Variability estimate

Standard error of the mean

Dispersion value

2.09

Notes
[294] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

Secondary: Percent Change From Baseline in HDL-C at Week 12

Top of page

End point title

Percent Change From Baseline in HDL-C at Week 12

End point description

Efficacy analyses were performed on the full analysis set. Least squares (LS) means are from a repeated measures linear effects model; missing values were not imputed.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	A10 PBO Q2W	A10 PBO QM	A10 EZE (Q2W)	A10 EZE (QM)	A10 EvoMab Q2W	A10 EvoMab QM	A80 PBO Q2W	A80 PBO QM	A80 EZE (Q2W)	A80 EZE (QM)	A80 EvoMab Q2W	A80 EvoMab QM	R5 PBO Q2W	R5 PBO QM	R5 EvoMab Q2W	R5 EvoMab QM	R40 PBO Q2W	R40 PBO QM	R40 EvoMab Q2W	R40 EvoMab QM	S40 PBO Q2W	S40 PBO QM	S40 EvoMab Q2W	S40 EvoMab QM
Number of subjects analysed	56	55	56	55	110	110	55	55	56	54	109	110	58	57	113	115	56	55	111	112	56	55	112	115
Units: percent change
least squares mean (standard error)	0.22 ( 1.72 )	0.01 ( 2.02 )	-1.76 ( 1.78 )	-0.4 ( 1.99 )	7.04 ( 1.23 )	7.88 ( 1.42 )	5.02 ( 1.88 )	0.3 ( 2.01 )	0.62 ( 1.83 )	0.21 ( 2.01 )	9.09 ( 1.29 )	7.36 ( 1.43 )	2.87 ( 1.87 )	-0.16 ( 2.64 )	6.07 ( 1.35 )	7.18 ( 1.87 )	-0.39 ( 1.86 )	0.73 ( 1.98 )	4.65 ( 1.34 )	5.57 ( 1.37 )	1.14 ( 2.96 )	-2.65 ( 2.87 )	10.92 ( 2.38 )	6.41 ( 2.34 )

A10: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A10 PBO Q2W v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.034 ^[295]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

6.83

Confidence interval

level

95%

sides

2-sided

lower limit

2.66

upper limit

10.99

Variability estimate

Standard error of the mean

Dispersion value

2.11

Notes
[295] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Placebo QM

Comparison groups

A10 PBO QM v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.017 ^[296]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

7.87

Confidence interval

level

95%

sides

2-sided

lower limit

3.01

upper limit

12.73

Variability estimate

Standard error of the mean

Dispersion value

2.46

Notes
[296] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A10 EZE (Q2W) v A10 EvoMab Q2W

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[297]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

8.81

Confidence interval

level

95%

sides

2-sided

lower limit

4.58

upper limit

13.03

Variability estimate

Standard error of the mean

Dispersion value

2.14

Notes
[297] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A10: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A10 EZE (QM) v A10 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006 ^[298]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

8.28

Confidence interval

level

95%

sides

2-sided

lower limit

3.46

upper limit

13.11

Variability estimate

Standard error of the mean

Dispersion value

2.45

Notes
[298] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Placebo Q2W

Comparison groups

A80 PBO Q2W v A80 EvoMab Q2W

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.85 ^[299]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

4.07

Confidence interval

level

95%

sides

2-sided

lower limit

-0.42

upper limit

8.57

Variability estimate

Standard error of the mean

Dispersion value

2.28

Notes
[299] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Placebo QM

Comparison groups

A80 PBO QM v A80 EvoMab QM

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[300]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

7.05

Confidence interval

level

95%

sides

2-sided

lower limit

2.22

upper limit

11.89

Variability estimate

Standard error of the mean

Dispersion value

2.45

Notes
[300] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab Q2W vs Ezetimibe (Q2W)

Comparison groups

A80 EZE (Q2W) v A80 EvoMab Q2W

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[301]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

8.47

Confidence interval

level

95%

sides

2-sided

lower limit

4.07

upper limit

12.87

Variability estimate

Standard error of the mean

Dispersion value

2.23

Notes
[301] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

A80: Evolocumab QM vs Ezetimibe (QM)

Comparison groups

A80 EZE (QM) v A80 EvoMab QM

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[302]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

7.14

Confidence interval

level

95%

sides

2-sided

lower limit

2.29

upper limit

11.99

Variability estimate

Standard error of the mean

Dispersion value

2.46

Notes
[302] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R5 PBO Q2W v R5 EvoMab Q2W

Number of subjects included in analysis

171

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[303]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

3.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.33

upper limit

7.73

Variability estimate

Standard error of the mean

Dispersion value

2.3

Notes
[303] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R5: Evolocumab QM vs Placebo QM

Comparison groups

R5 PBO QM v R5 EvoMab QM

Number of subjects included in analysis

172

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.01 ^[304]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

7.35

Confidence interval

level

95%

sides

2-sided

lower limit

0.97

upper limit

13.72

Variability estimate

Standard error of the mean

Dispersion value

3.23

Notes
[304] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

R40 PBO Q2W v R40 EvoMab Q2W

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.013 ^[305]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

5.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.52

upper limit

9.56

Variability estimate

Standard error of the mean

Dispersion value

2.29

Notes
[305] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

R40: Evolocumab QM vs Placebo QM

Comparison groups

R40 PBO QM v R40 EvoMab QM

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[306]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

4.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.07

upper limit

9.6

Variability estimate

Standard error of the mean

Dispersion value

2.41

Notes
[306] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab Q2W vs Placebo Q2W

Comparison groups

S40 PBO Q2W v S40 EvoMab Q2W

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[307]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

9.78

Confidence interval

level

95%

sides

2-sided

lower limit

4.05

upper limit

15.51

Variability estimate

Standard error of the mean

Dispersion value

2.9

Notes
[307] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

S40: Evolocumab QM vs Placebo QM

Comparison groups

S40 PBO QM v S40 EvoMab QM

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[308]

Method

Repeated measures linear effects model

Parameter type

LS Mean Treatment Difference

Point estimate

9.06

Confidence interval

level

95%

sides

2-sided

lower limit

4.4

upper limit

13.72

Variability estimate

Standard error of the mean

Dispersion value

2.36

Notes
[308] - The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit. Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.

Adverse events

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Timeframe for reporting adverse events

From the first dose of blinded investigational product until the end of the study (up to 14 weeks).

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

17.0

Reporting group title

A10 PBO Q2W

Reporting group description

Reporting group title

A10 PBO QM

Reporting group description

Reporting group title

A10 EZE (Q2W)

Reporting group description

Reporting group title

A10 EZE (QM)

Reporting group description

Reporting group title

A10 EvoMab Q2W

Reporting group description

Reporting group title

A10 EvoMab QM

Reporting group description

Reporting group title

A80 PBO Q2W

Reporting group description

Reporting group title

A80 PBO QM

Reporting group description

Reporting group title

A80 EZE (Q2W)

Reporting group description

Reporting group title

A80 EZE (QM)

Reporting group description

Reporting group title

A80 EvoMab Q2W

Reporting group description

Reporting group title

A80 EvoMab QM

Reporting group description

Reporting group title

R5 PBO Q2W

Reporting group description

Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks.

Reporting group title

R5 PBO QM

Reporting group description

Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month for up to 12 weeks.

Reporting group title

R5 EvoMab Q2W

Reporting group description

Reporting group title

R5 EvoMab QM

Reporting group description

Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.

Reporting group title

R40 PBO Q2W

Reporting group description

Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks.

Reporting group title

R40 PBO QM

Reporting group description

Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month for up to 12 weeks.

Reporting group title

R40 EvoMab Q2W

Reporting group description

Reporting group title

R40 EvoMab QM

Reporting group description

Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.

Reporting group title

S40 PBO Q2W

Reporting group description

Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks.

Reporting group title

S40 PBO QM

Reporting group description

Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month for up to 12 weeks.

Reporting group title

S40 EvoMab Q2W

Reporting group description

Reporting group title

S40 EvoMab QM

Reporting group description

Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.

A10 PBO Q2W

A10 PBO QM

A10 EZE (Q2W)

A10 EZE (QM)

A10 EvoMab Q2W

A10 EvoMab QM

A80 PBO Q2W

A80 PBO QM

A80 EZE (Q2W)

A80 EZE (QM)

A80 EvoMab Q2W

A80 EvoMab QM

R5 PBO Q2W

R5 PBO QM

R5 EvoMab Q2W

R5 EvoMab QM

R40 PBO Q2W

R40 PBO QM

R40 EvoMab Q2W

R40 EvoMab QM

S40 PBO Q2W

S40 PBO QM

S40 EvoMab Q2W

S40 EvoMab QM

Total subjects affected by serious adverse events

subjects affected / exposed

1 / 56 (1.79%)

2 / 55 (3.64%)

0 / 56 (0.00%)

0 / 55 (0.00%)

4 / 110 (3.64%)

2 / 110 (1.82%)

2 / 55 (3.64%)

1 / 55 (1.82%)

1 / 56 (1.79%)

1 / 54 (1.85%)

3 / 109 (2.75%)

1 / 110 (0.91%)

1 / 58 (1.72%)

2 / 57 (3.51%)

3 / 113 (2.65%)

3 / 115 (2.61%)

2 / 56 (3.57%)

1 / 55 (1.82%)

1 / 111 (0.90%)

3 / 112 (2.68%)

0 / 56 (0.00%)

1 / 55 (1.82%)

2 / 112 (1.79%)

1 / 115 (0.87%)

number of deaths (all causes)

number of deaths resulting from adverse events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bladder neoplasm

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

1 / 56 (1.79%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Colon cancer metastatic

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

1 / 112 (0.89%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lung adenocarcinoma metastatic

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

1 / 113 (0.88%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ovarian cancer

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

1 / 57 (1.75%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pleomorphic adenoma

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

1 / 58 (1.72%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

Aortic aneurysm

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

1 / 109 (0.92%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypertensive crisis

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

1 / 54 (1.85%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Orthostatic hypotension

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

1 / 111 (0.90%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Peripheral artery stenosis

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

1 / 55 (1.82%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Surgical and medical procedures

Hip arthroplasty

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

1 / 110 (0.91%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Reproductive system and breast disorders

Breast pain

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

1 / 110 (0.91%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Pulmonary oedema

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

1 / 109 (0.92%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

Affective disorder

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

1 / 110 (0.91%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Investigations

Troponin increased

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

1 / 54 (1.85%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Injury

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

1 / 112 (0.89%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Radius fracture

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

1 / 115 (0.87%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Acute coronary syndrome

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

1 / 110 (0.91%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Acute myocardial infarction

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

1 / 110 (0.91%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

1 / 115 (0.87%)

1 / 56 (1.79%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Myocardial infarction

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

1 / 109 (0.92%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ventricular fibrillation

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

1 / 109 (0.92%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Cerebrovascular accident

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

1 / 56 (1.79%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Coma

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

1 / 109 (0.92%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Grand mal convulsion

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

1 / 55 (1.82%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ischaemic stroke

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

1 / 112 (0.89%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Abdominal pain upper

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

1 / 113 (0.88%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal haemorrhage

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

1 / 55 (1.82%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

1 / 55 (1.82%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hiatus hernia

subjects affected / exposed

1 / 56 (1.79%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

Cholecystitis

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

1 / 112 (0.89%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Drug-induced liver injury

subjects affected / exposed

0 / 56 (0.00%)

1 / 55 (1.82%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

Glomerulonephritis acute

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

1 / 112 (0.89%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal failure acute

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

1 / 115 (0.87%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Myalgia

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

1 / 55 (1.82%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Rotator cuff syndrome

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

1 / 110 (0.91%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Spinal pain

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

1 / 115 (0.87%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Infections and infestations

Campylobacter infection

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

1 / 113 (0.88%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastroenteritis

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

1 / 55 (1.82%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Herpes simplex meningoencephalitis

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

1 / 55 (1.82%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Infected bites

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

1 / 109 (0.92%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

1 / 110 (0.91%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia mycoplasmal

subjects affected / exposed

0 / 56 (0.00%)

1 / 55 (1.82%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pyelonephritis acute

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

1 / 110 (0.91%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urinary tract infection bacterial

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

1 / 57 (1.75%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 111 (0.00%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

Dehydration

subjects affected / exposed

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 110 (0.00%)

0 / 55 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 110 (0.00%)

0 / 58 (0.00%)

0 / 57 (0.00%)

0 / 113 (0.00%)

0 / 115 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

1 / 111 (0.90%)

0 / 112 (0.00%)

0 / 56 (0.00%)

0 / 55 (0.00%)

0 / 112 (0.00%)

0 / 115 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	A10 PBO Q2W	A10 PBO QM	A10 EZE (Q2W)	A10 EZE (QM)	A10 EvoMab Q2W	A10 EvoMab QM	A80 PBO Q2W	A80 PBO QM	A80 EZE (Q2W)	A80 EZE (QM)	A80 EvoMab Q2W	A80 EvoMab QM	R5 PBO Q2W	R5 PBO QM	R5 EvoMab Q2W	R5 EvoMab QM	R40 PBO Q2W	R40 PBO QM	R40 EvoMab Q2W	R40 EvoMab QM	S40 PBO Q2W	S40 PBO QM	S40 EvoMab Q2W	S40 EvoMab QM
Total subjects affected by non serious adverse events
subjects affected / exposed	5 / 56 (8.93%)	3 / 55 (5.45%)	9 / 56 (16.07%)	6 / 55 (10.91%)	9 / 110 (8.18%)	7 / 110 (6.36%)	7 / 55 (12.73%)	13 / 55 (23.64%)	8 / 56 (14.29%)	2 / 54 (3.70%)	11 / 109 (10.09%)	9 / 110 (8.18%)	11 / 58 (18.97%)	1 / 57 (1.75%)	6 / 113 (5.31%)	9 / 115 (7.83%)	3 / 56 (5.36%)	8 / 55 (14.55%)	5 / 111 (4.50%)	8 / 112 (7.14%)	3 / 56 (5.36%)	5 / 55 (9.09%)	18 / 112 (16.07%)	11 / 115 (9.57%)
Nervous system disorders
Dizziness
subjects affected / exposed	0 / 56 (0.00%)	0 / 55 (0.00%)	2 / 56 (3.57%)	1 / 55 (1.82%)	1 / 110 (0.91%)	1 / 110 (0.91%)	1 / 55 (1.82%)	1 / 55 (1.82%)	1 / 56 (1.79%)	1 / 54 (1.85%)	0 / 109 (0.00%)	1 / 110 (0.91%)	3 / 58 (5.17%)	0 / 57 (0.00%)	1 / 113 (0.88%)	2 / 115 (1.74%)	0 / 56 (0.00%)	0 / 55 (0.00%)	0 / 111 (0.00%)	1 / 112 (0.89%)	1 / 56 (1.79%)	0 / 55 (0.00%)	3 / 112 (2.68%)	1 / 115 (0.87%)
occurrences all number	0	0	2	1	1	1	1	1	1	1	0	1	3	0	1	2	0	0	0	1	1	0	3	1
Headache
subjects affected / exposed	1 / 56 (1.79%)	1 / 55 (1.82%)	1 / 56 (1.79%)	4 / 55 (7.27%)	1 / 110 (0.91%)	0 / 110 (0.00%)	2 / 55 (3.64%)	2 / 55 (3.64%)	0 / 56 (0.00%)	0 / 54 (0.00%)	1 / 109 (0.92%)	3 / 110 (2.73%)	3 / 58 (5.17%)	0 / 57 (0.00%)	1 / 113 (0.88%)	1 / 115 (0.87%)	2 / 56 (3.57%)	1 / 55 (1.82%)	2 / 111 (1.80%)	3 / 112 (2.68%)	2 / 56 (3.57%)	1 / 55 (1.82%)	2 / 112 (1.79%)	5 / 115 (4.35%)
occurrences all number	1	1	1	4	1	0	3	2	0	0	1	3	3	0	1	2	2	1	3	3	2	1	2	6
Gastrointestinal disorders
Constipation
subjects affected / exposed	3 / 56 (5.36%)	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 55 (0.00%)	0 / 110 (0.00%)	0 / 110 (0.00%)	1 / 55 (1.82%)	0 / 55 (0.00%)	1 / 56 (1.79%)	0 / 54 (0.00%)	0 / 109 (0.00%)	0 / 110 (0.00%)	0 / 58 (0.00%)	0 / 57 (0.00%)	1 / 113 (0.88%)	0 / 115 (0.00%)	0 / 56 (0.00%)	0 / 55 (0.00%)	0 / 111 (0.00%)	0 / 112 (0.00%)	0 / 56 (0.00%)	0 / 55 (0.00%)	2 / 112 (1.79%)	0 / 115 (0.00%)
occurrences all number	3	0	0	0	0	0	1	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	2	0
Diarrhoea
subjects affected / exposed	0 / 56 (0.00%)	0 / 55 (0.00%)	0 / 56 (0.00%)	1 / 55 (1.82%)	2 / 110 (1.82%)	0 / 110 (0.00%)	1 / 55 (1.82%)	4 / 55 (7.27%)	1 / 56 (1.79%)	0 / 54 (0.00%)	4 / 109 (3.67%)	2 / 110 (1.82%)	0 / 58 (0.00%)	1 / 57 (1.75%)	0 / 113 (0.00%)	2 / 115 (1.74%)	1 / 56 (1.79%)	1 / 55 (1.82%)	0 / 111 (0.00%)	1 / 112 (0.89%)	0 / 56 (0.00%)	1 / 55 (1.82%)	1 / 112 (0.89%)	0 / 115 (0.00%)
occurrences all number	0	0	0	1	2	0	2	4	1	0	5	2	0	1	0	2	1	1	0	1	0	1	1	0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 56 (0.00%)	0 / 55 (0.00%)	3 / 56 (5.36%)	1 / 55 (1.82%)	2 / 110 (1.82%)	1 / 110 (0.91%)	2 / 55 (3.64%)	2 / 55 (3.64%)	2 / 56 (3.57%)	1 / 54 (1.85%)	3 / 109 (2.75%)	0 / 110 (0.00%)	4 / 58 (6.90%)	0 / 57 (0.00%)	1 / 113 (0.88%)	2 / 115 (1.74%)	0 / 56 (0.00%)	5 / 55 (9.09%)	2 / 111 (1.80%)	1 / 112 (0.89%)	0 / 56 (0.00%)	1 / 55 (1.82%)	6 / 112 (5.36%)	2 / 115 (1.74%)
occurrences all number	0	0	3	1	2	1	2	2	2	1	3	0	4	0	1	2	0	6	2	1	0	1	6	2
Muscle spasms
subjects affected / exposed	0 / 56 (0.00%)	0 / 55 (0.00%)	1 / 56 (1.79%)	2 / 55 (3.64%)	3 / 110 (2.73%)	4 / 110 (3.64%)	1 / 55 (1.82%)	2 / 55 (3.64%)	3 / 56 (5.36%)	0 / 54 (0.00%)	2 / 109 (1.83%)	1 / 110 (0.91%)	1 / 58 (1.72%)	0 / 57 (0.00%)	2 / 113 (1.77%)	0 / 115 (0.00%)	0 / 56 (0.00%)	1 / 55 (1.82%)	0 / 111 (0.00%)	1 / 112 (0.89%)	0 / 56 (0.00%)	1 / 55 (1.82%)	3 / 112 (2.68%)	1 / 115 (0.87%)
occurrences all number	0	0	1	2	3	4	1	2	3	0	2	1	1	0	2	0	0	1	0	1	0	1	3	1
Myalgia
subjects affected / exposed	2 / 56 (3.57%)	2 / 55 (3.64%)	2 / 56 (3.57%)	0 / 55 (0.00%)	0 / 110 (0.00%)	1 / 110 (0.91%)	0 / 55 (0.00%)	3 / 55 (5.45%)	1 / 56 (1.79%)	1 / 54 (1.85%)	1 / 109 (0.92%)	2 / 110 (1.82%)	1 / 58 (1.72%)	0 / 57 (0.00%)	0 / 113 (0.00%)	2 / 115 (1.74%)	0 / 56 (0.00%)	1 / 55 (1.82%)	1 / 111 (0.90%)	1 / 112 (0.89%)	0 / 56 (0.00%)	1 / 55 (1.82%)	1 / 112 (0.89%)	3 / 115 (2.61%)
occurrences all number	2	2	2	0	0	1	0	3	1	1	2	2	1	0	0	2	0	1	1	1	0	2	1	3

More information

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Were there any global substantial amendments to the protocol? Yes

01 Aug 2012

- added testing for prior or existing HCV infection in high risk individuals and evaluation of viral load in those who showed evidence thereof - clarified that subjects with known sensitivity to the ‘active substances or their excipients’ were excluded - added urine pregnancy testing at day 1, week 4, and week 8 for women of childbearing potential

10 Oct 2012

- added the LAPLACE-2 study acronym and short title - included a lipid stabilization period for background statin therapy - added new evolocumab formulation and autoinjectors to allow administration of investigational product in a home-use setting, revised schedule of assessment and description of procedures to replace week 4 and 6 visits with home-use IP administration, added reporting requirements for product/device complaints - updated program status in evolocumab background section - provide instruction regarding missed ezetimibe doses - added subjects with a history of HCV infection to the HCV antibody testing and viral load monitoring, if positive - updated sections on collection and reporting of adverse events and serious adverse events, including adding device-related AEs, and the serious adverse event contingency form - move change from baseline in VLDL-C at week 12 from tertiary to secondary endpoints - added transient ischemic attacks and non-coronary revascularization as exploratory endpoints - implemented minor clarifications and error corrections

10 Dec 2012

- added the LDL-C endpoint of mean percent change from baseline at weeks 10 and 12 as a co-primary endpoint - added the means of weeks 10 and 12 as co-secondary endpoints to all secondary endpoints - added an alert threshold for elevated triglycerides - added publication references for primary result publications of phase 2 studies MENDEL and LAPLACE - introduce the simplified terminology of once-monthly (QM) dosing - implemented minor clarifications and error corrections

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Double-blind, Randomized, Placebo and Ezetimibe Controlled, Multicenter Study to Evaluate Safety, Tolerability and Efficacy of AMG 145 on LDL-C in Combination With Statin Therapy in Subjects With Primary Hypercholesterolemia and Mixed Dyslipidemia

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12

Primary: Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12

Primary: Mean Percent Change From Baseline in LDL-C at Weeks 10 and 12

Primary: Mean Percent Change From Baseline in LDL-C at Weeks 10 and 12

Secondary: Mean Change From Baseline in LDL-C at Weeks 10 and 12

Secondary: Mean Change From Baseline in LDL-C at Weeks 10 and 12

Secondary: Change From Baseline in LDL-C at Week 12

Secondary: Change From Baseline in LDL-C at Week 12

Secondary: Mean Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (non-HDL-C) at Weeks 10 and 12

Secondary: Mean Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (non-HDL-C) at Weeks 10 and 12

Secondary: Percent Change From Baseline in non-HDL-C at Week 12

Secondary: Percent Change From Baseline in non-HDL-C at Week 12

Secondary: Mean Percent Change From Baseline in Apolipoprotein B at Weeks 10 and 12

Secondary: Mean Percent Change From Baseline in Apolipoprotein B at Weeks 10 and 12

Secondary: Percent Change From Baseline in Apolipoprotein B at Week 12

Secondary: Percent Change From Baseline in Apolipoprotein B at Week 12

Secondary: Mean Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Weeks 10 and 12

Secondary: Mean Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Weeks 10 and 12

Secondary: Mean Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12

Secondary: Mean Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12

Secondary: Mean Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Weeks 10 and 12

Secondary: Mean Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Weeks 10 and 12

Secondary: Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12

Secondary: Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12

Secondary: Mean Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Weeks 10 and 12

Secondary: Mean Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Weeks 10 and 12

Secondary: Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12

Secondary: Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12

Secondary: Mean Percent Change From Baseline in Lipoprotein(a) at Weeks 10 and 12

Secondary: Mean Percent Change From Baseline in Lipoprotein(a) at Weeks 10 and 12

Secondary: Percent Change From Baseline in Lipoprotein(a) at Week 12

Secondary: Percent Change From Baseline in Lipoprotein(a) at Week 12

Secondary: Mean Percent Change From Baseline in Triglycerides at Weeks 10 and 12

Secondary: Mean Percent Change From Baseline in Triglycerides at Weeks 10 and 12

Secondary: Percent Change From Baseline in Triglycerides at Week 12

Secondary: Percent Change From Baseline in Triglycerides at Week 12

Secondary: Mean Percent Change From Baseline in Very Low-Density Cholesterol (VLDL-C) at Weeks 10 and 12

Secondary: Mean Percent Change From Baseline in Very Low-Density Cholesterol (VLDL-C) at Weeks 10 and 12

Secondary: Percent Change From Baseline in VLDL-C at Week 12

Secondary: Percent Change From Baseline in VLDL-C at Week 12

Secondary: Mean percent Change From Baseline in HDL-C at Weeks 10 and 12

Secondary: Mean percent Change From Baseline in HDL-C at Weeks 10 and 12

Secondary: Percent Change From Baseline in HDL-C at Week 12

Secondary: Percent Change From Baseline in HDL-C at Week 12

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Double-blind, Randomized, Placebo and Ezetimibe Controlled, Multicenter Study to Evaluate Safety, Tolerability and Efficacy of AMG 145 on LDL-C in Combination With Statin Therapy in Subjects With Primary Hypercholesterolemia and Mixed Dyslipidemia