## Protocol Section
### Identification Module
**NCT ID:** NCT01516879

**Acronym:** DESCARTES

**Brief Title:** Durable Effect of PCSK9 Antibody CompARed wiTh placEbo Study

**Official Title:** A Double-Blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Long-Term Tolerability and Durable Efficacy of AMG 145 (Evolocumab) on LDL-C in Hyperlipidemic Subjects

#### Organization Study ID Info
**ID:** 20110109
#### Organization
**Class:** INDUSTRY
**Full Name:** Amgen
### Status Module
#### Completion Date
**Date:** 2013-10-14

**Type:** ACTUAL

#### Disp First Post Date
**Date:** 2014-05-28

**Type:** ESTIMATED

**Disp First Submit Date:** 2014-05-15
**Disp First Submit QC Date:** 2014-05-15

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2022-07-22

**Type:** ACTUAL

**Last Update Submit Date:** 2022-07-15

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2013-10-14

**Type:** ACTUAL

#### Results First Post Date
**Date:** 2015-09-29

**Type:** ESTIMATED

**Results First Submit Date:** 2015-08-28

**Results First Submit QC Date:** 2015-08-28

#### Start Date
**Date:** 2012-01-05

**Type:** ACTUAL

**Status Verified Date:** 2022-07

#### Study First Post Date
**Date:** 2012-01-25
**Type:** ESTIMATED
**Study First Submit Date:** 2012-01-18
**Study First Submit QC Date:** 2012-01-20
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Amgen

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** To evaluate the efficacy, safety, and tolerability of 52 weeks of subcutaneous (SC) evolocumab (AMG 145) compared with placebo when added to assigned background lipid-lowering therapy.

**Detailed Description:** Eligible participants with screening central laboratory low-density lipoprotein cholesterol (LDL-C) values ≥ 75 mg/dL (1.9 mmol/L) were instructed to follow National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP) Therapeutic Lifestyle Changes (TLC) diet and were assigned to 1 of the following 4 background lipid-lowering therapies for a 4-week stabilization period based upon their screening LDL-C and its distance from the individual's required goal as stipulated by their NCEP ATP III risk category:

1. no drug therapy required - diet alone
2. low dose drug therapy required - diet plus atorvastatin 10 mg orally (PO) once daily (QD)
3. high dose drug therapy required - diet plus atorvastatin 80 mg PO QD
4. maximal drug therapy required - diet plus atorvastatin 80 mg PO QD plus ezetimibe 10 mg PO QD.

If the participant met entry criteria at the end of the lipid stabilization period they were randomized 2:1 to receive evolocumab 420 mg or placebo subcutaneously once a month for 52 weeks in addition to their background therapy.

### Conditions Module

**Conditions:**

- Hypercholesterolemia

**Keywords:**

- Cholesterol

- High Cholesterol

- Elevated Cholesterol

- Raised Cholesterol

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 905

**Type:** ACTUAL

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.

**Intervention Names:**

- Biological: Evolocumab

- Drug: Atorvastatin

- Drug: Ezetimibe

- Other: Diet Only

**Label:** Evolocumab

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.

**Intervention Names:**

- Biological: Placebo

- Drug: Atorvastatin

- Drug: Ezetimibe

- Other: Diet Only

**Label:** Placebo

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Evolocumab

**Description:** Administered by subcutaneous injection once a month

**Name:** Evolocumab

**Other Names:**

- AMG 145

- Repatha

**Type:** BIOLOGICAL

#### Intervention 2

**Arm Group Labels:**

- Placebo

**Description:** Administered by subcutaneous injection once a month

**Name:** Placebo

**Type:** BIOLOGICAL

#### Intervention 3

**Arm Group Labels:**

- Evolocumab

- Placebo

**Description:** Background lipid lowering therapy: 10 mg or 80 mg atorvastatin orally once daily.

**Name:** Atorvastatin

**Type:** DRUG

#### Intervention 4

**Arm Group Labels:**

- Evolocumab

- Placebo

**Description:** Background lipid lowering therapy: ezetimibe 10 mg orally once a day

**Name:** Ezetimibe

**Type:** DRUG

#### Intervention 5

**Arm Group Labels:**

- Evolocumab

- Placebo

**Description:** Diet only, no lipid lowering background drug given

**Name:** Diet Only

**Type:** OTHER

### Outcomes Module

#### Primary Outcomes

**Description:** Cholesterol was measured by means of ultracentrifugation.

**Measure:** Percent Change From Baseline in LDL-C at Week 52

**Time Frame:** Baseline and Week 52

#### Secondary Outcomes

**Description:** Cholesterol was measured by means of ultracentrifugation.

**Measure:** Change From Baseline in LDL-C at Week 52

**Time Frame:** Baseline and Week 52

**Description:** An LDL-C response is defined as LDL-C level \< 70 mg/dL (1.8 mmol/L) at Week 52.

**Measure:** Percentage of Participants With an LDL-C Response at Week 52

**Time Frame:** Week 52

**Description:** Cholesterol was measured by means of ultracentrifugation.

**Measure:** Percent Change From Baseline in LDL-C at Week 12

**Time Frame:** Baseline and Week 12

**Measure:** Percent Change From Baseline in Total Cholesterol at Week 12

**Time Frame:** Baseline and Week 12

**Measure:** Percent Change From Baseline in Total Cholesterol at Week 52

**Time Frame:** Baseline and Week 52

**Measure:** Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at Week 52

**Time Frame:** Baseline and Week 52

**Measure:** Percent Change From Baseline in Apolipoprotein B at Week 52

**Time Frame:** Baseline and Week 52

**Measure:** Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 52

**Time Frame:** Baseline and Week 52

**Measure:** Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 52

**Time Frame:** Baseline and Week 52

**Measure:** Percent Change From Baseline in Lipoprotein(a) at Week 52

**Time Frame:** Baseline and Week 52

**Measure:** Percent Change From Baseline in Triglycerides at Week 52

**Time Frame:** Baseline and Week 52

**Measure:** Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 52

**Time Frame:** Baseline and Week 52

**Description:** Cholesterol was measured by means of ultracentrifugation.

**Measure:** Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at Week 52

**Time Frame:** Baseline and Week 52

**Description:** Cholesterol was measured by means of ultracentrifugation.

**Measure:** Percent Change From Week 12 to Week 52 in LDL-C

**Time Frame:** Week 12 and Week 52

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Subject has provided informed consent.
* Fasting LDL-C ≥ 75 mg/dL and meeting the following LDL-C values on background lipid-lowering therapy:

  * \< 100 mg/dL for subjects with diagnosed coronary heart disease (CHD) or CHD risk equivalent
  * \< 130 mg/dL for subjects without diagnosed CHD or CHD risk equivalent
  * OR on maximal background lipid-lowering therapy defined as atorvastatin 80 mg PO QD and ezetimibe 10 mg PO QD
* Fasting triglycerides ≤ 400 mg/dL

Exclusion Criteria:

* New York Heart Association (NYHA) II-IV heart failure, or last known left ventricular ejection fraction \< 30%
* Uncontrolled cardiac arrhythmia
* Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months prior to randomization, type 1 diabetes, newly diagnosed or poorly controlled type 2 diabetes
* Uncontrolled hypertension

**Maximum Age:** 80 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Birmingham

**Country:** United States

**Facility:** Research Site

**State:** Alabama

**Zip:** 35216

**Location 2:**

**City:** Little Rock

**Country:** United States

**Facility:** Research Site

**State:** Arkansas

**Zip:** 72205

**Location 3:**

**City:** Anaheim

**Country:** United States

**Facility:** Research Site

**State:** California

**Zip:** 92801

**Location 4:**

**City:** Encinitas

**Country:** United States

**Facility:** Research Site

**State:** California

**Zip:** 92024

**Location 5:**

**City:** Spring Valley

**Country:** United States

**Facility:** Research Site

**State:** California

**Zip:** 91978

**Location 6:**

**City:** Westlake Village

**Country:** United States

**Facility:** Research Site

**State:** California

**Zip:** 91361

**Location 7:**

**City:** DeLand

**Country:** United States

**Facility:** Research Site

**State:** Florida

**Zip:** 32720

**Location 8:**

**City:** Jacksonville

**Country:** United States

**Facility:** Research Site

**State:** Florida

**Zip:** 32204

**Location 9:**

**City:** Jacksonville

**Country:** United States

**Facility:** Research Site

**State:** Florida

**Zip:** 32216

**Location 10:**

**City:** Ponte Vedra

**Country:** United States

**Facility:** Research Site

**State:** Florida

**Zip:** 32081

**Location 11:**

**City:** Atlanta

**Country:** United States

**Facility:** Research Site

**State:** Georgia

**Zip:** 30338

**Location 12:**

**City:** Atlanta

**Country:** United States

**Facility:** Research Site

**State:** Georgia

**Zip:** 30342

**Location 13:**

**City:** Savannah

**Country:** United States

**Facility:** Research Site

**State:** Georgia

**Zip:** 31406

**Location 14:**

**City:** Chicago

**Country:** United States

**Facility:** Research Site

**State:** Illinois

**Zip:** 60610

**Location 15:**

**City:** Indianapolis

**Country:** United States

**Facility:** Research Site

**State:** Indiana

**Zip:** 46260

**Location 16:**

**City:** Louisville

**Country:** United States

**Facility:** Research Site

**State:** Kentucky

**Zip:** 40213

**Location 17:**

**City:** Auburn

**Country:** United States

**Facility:** Research Site

**State:** Maine

**Zip:** 04210

**Location 18:**

**City:** Bethesda

**Country:** United States

**Facility:** Research Site

**State:** Maryland

**Zip:** 20817

**Location 19:**

**City:** Chevy Chase

**Country:** United States

**Facility:** Research Site

**State:** Maryland

**Zip:** 20815

**Location 20:**

**City:** Columbia

**Country:** United States

**Facility:** Research Site

**State:** Maryland

**Zip:** 21045

**Location 21:**

**City:** Brockton

**Country:** United States

**Facility:** Research Site

**State:** Massachusetts

**Zip:** 02301

**Location 22:**

**City:** Saint Paul

**Country:** United States

**Facility:** Research Site

**State:** Minnesota

**Zip:** 55114

**Location 23:**

**City:** Olive Branch

**Country:** United States

**Facility:** Research Site

**State:** Mississippi

**Zip:** 38654

**Location 24:**

**City:** Las Vegas

**Country:** United States

**Facility:** Research Site

**State:** Nevada

**Zip:** 89148

**Location 25:**

**City:** Endwell

**Country:** United States

**Facility:** Research Site

**State:** New York

**Zip:** 13760

**Location 26:**

**City:** New Windsor

**Country:** United States

**Facility:** Research Site

**State:** New York

**Zip:** 12553

**Location 27:**

**City:** Raleigh

**Country:** United States

**Facility:** Research Site

**State:** North Carolina

**Zip:** 27609

**Location 28:**

**City:** Raleigh

**Country:** United States

**Facility:** Research Site

**State:** North Carolina

**Zip:** 27612

**Location 29:**

**City:** Fargo

**Country:** United States

**Facility:** Research Site

**State:** North Dakota

**Zip:** 58103

**Location 30:**

**City:** Akron

**Country:** United States

**Facility:** Research Site

**State:** Ohio

**Zip:** 44311

**Location 31:**

**City:** Cincinnati

**Country:** United States

**Facility:** Research Site

**State:** Ohio

**Zip:** 45219

**Location 32:**

**City:** Cincinnati

**Country:** United States

**Facility:** Research Site

**State:** Ohio

**Zip:** 45227

**Location 33:**

**City:** Cincinnati

**Country:** United States

**Facility:** Research Site

**State:** Ohio

**Zip:** 45246

**Location 34:**

**City:** Norman

**Country:** United States

**Facility:** Research Site

**State:** Oklahoma

**Zip:** 73069

**Location 35:**

**City:** Duncansville

**Country:** United States

**Facility:** Research Site

**State:** Pennsylvania

**Zip:** 16635

**Location 36:**

**City:** Mount Pleasant

**Country:** United States

**Facility:** Research Site

**State:** South Carolina

**Zip:** 29464

**Location 37:**

**City:** Rapid City

**Country:** United States

**Facility:** Research Site

**State:** South Dakota

**Zip:** 57702

**Location 38:**

**City:** Houston

**Country:** United States

**Facility:** Research Site

**State:** Texas

**Zip:** 77030

**Location 39:**

**City:** Richmond

**Country:** United States

**Facility:** Research Site

**State:** Virginia

**Zip:** 23294

**Location 40:**

**City:** Renton

**Country:** United States

**Facility:** Research Site

**State:** Washington

**Zip:** 98057

**Location 41:**

**City:** Seattle

**Country:** United States

**Facility:** Research Site

**State:** Washington

**Zip:** 98104

**Location 42:**

**City:** Camperdown

**Country:** Australia

**Facility:** Research Site

**State:** New South Wales

**Zip:** 2015

**Location 43:**

**City:** Maroubra

**Country:** Australia

**Facility:** Research Site

**State:** New South Wales

**Zip:** 2035

**Location 44:**

**City:** Carina Heights

**Country:** Australia

**Facility:** Research Site

**State:** Queensland

**Zip:** 4152

**Location 45:**

**City:** Milton

**Country:** Australia

**Facility:** Research Site

**State:** Queensland

**Zip:** 4064

**Location 46:**

**City:** Fitzroy

**Country:** Australia

**Facility:** Research Site

**State:** Victoria

**Zip:** 3065

**Location 47:**

**City:** Perth

**Country:** Australia

**Facility:** Research Site

**State:** Western Australia

**Zip:** 6000

**Location 48:**

**City:** Feldkirch

**Country:** Austria

**Facility:** Research Site

**Zip:** 6807

**Location 49:**

**City:** Innsbruck

**Country:** Austria

**Facility:** Research Site

**Zip:** 6020

**Location 50:**

**City:** Salzburg

**Country:** Austria

**Facility:** Research Site

**Zip:** 5020

**Location 51:**

**City:** Wels

**Country:** Austria

**Facility:** Research Site

**Zip:** 4600

**Location 52:**

**City:** AnthÃ©e

**Country:** Belgium

**Facility:** Research Site

**Zip:** 5520

**Location 53:**

**City:** Bruxelles

**Country:** Belgium

**Facility:** Research Site

**Zip:** 1200

**Location 54:**

**City:** Gent

**Country:** Belgium

**Facility:** Research Site

**Zip:** 9000

**Location 55:**

**City:** Gozee

**Country:** Belgium

**Facility:** Research Site

**Zip:** 6534

**Location 56:**

**City:** Ham

**Country:** Belgium

**Facility:** Research Site

**Zip:** 3945

**Location 57:**

**City:** Oostende

**Country:** Belgium

**Facility:** Research Site

**Zip:** 8400

**Location 58:**

**City:** Victoria

**Country:** Canada

**Facility:** Research Site

**State:** British Columbia

**Zip:** V8T 5G4

**Location 59:**

**City:** Bay Roberts

**Country:** Canada

**Facility:** Research Site

**State:** Newfoundland and Labrador

**Zip:** A0A 1G0

**Location 60:**

**City:** Cambridge

**Country:** Canada

**Facility:** Research Site

**State:** Ontario

**Zip:** N1R 6V6

**Location 61:**

**City:** London

**Country:** Canada

**Facility:** Research Site

**State:** Ontario

**Zip:** N5W 6A2

**Location 62:**

**City:** Newmarket

**Country:** Canada

**Facility:** Research Site

**State:** Ontario

**Zip:** L3Y 5G8

**Location 63:**

**City:** Sudbury

**Country:** Canada

**Facility:** Research Site

**State:** Ontario

**Zip:** P3C 5K7

**Location 64:**

**City:** Toronto

**Country:** Canada

**Facility:** Research Site

**State:** Ontario

**Zip:** M9V 4B4

**Location 65:**

**City:** Toronto

**Country:** Canada

**Facility:** Research Site

**State:** Ontario

**Zip:** M9W 4L6

**Location 66:**

**City:** Pointe-Claire

**Country:** Canada

**Facility:** Research Site

**State:** Quebec

**Zip:** H9R 3J1

**Location 67:**

**City:** Quebec

**Country:** Canada

**Facility:** Research Site

**Zip:** G1V 4M6

**Location 68:**

**City:** Brno

**Country:** Czechia

**Facility:** Research Site

**Zip:** 602 00

**Location 69:**

**City:** Brno

**Country:** Czechia

**Facility:** Research Site

**Zip:** 625 00

**Location 70:**

**City:** Chomutov

**Country:** Czechia

**Facility:** Research Site

**Zip:** 430 02

**Location 71:**

**City:** Hradec Kralove

**Country:** Czechia

**Facility:** Research Site

**Zip:** 500 05

**Location 72:**

**City:** Pardubice

**Country:** Czechia

**Facility:** Research Site

**Zip:** 530 02

**Location 73:**

**City:** Plzen

**Country:** Czechia

**Facility:** Research Site

**Zip:** 305 99

**Location 74:**

**City:** Praha 2

**Country:** Czechia

**Facility:** Research Site

**Zip:** 120 00

**Location 75:**

**City:** Praha 4

**Country:** Czechia

**Facility:** Research Site

**Zip:** 140 21

**Location 76:**

**City:** Praha 5

**Country:** Czechia

**Facility:** Research Site

**Zip:** 150 06

**Location 77:**

**City:** Slany

**Country:** Czechia

**Facility:** Research Site

**Zip:** 274 01

**Location 78:**

**City:** Aalborg

**Country:** Denmark

**Facility:** Research Site

**Zip:** 9000

**Location 79:**

**City:** Ballerup

**Country:** Denmark

**Facility:** Research Site

**Zip:** 2750

**Location 80:**

**City:** Vejle

**Country:** Denmark

**Facility:** Research Site

**Zip:** 7100

**Location 81:**

**City:** Baja

**Country:** Hungary

**Facility:** Research Site

**Zip:** 6500

**Location 82:**

**City:** Budapest

**Country:** Hungary

**Facility:** Research Site

**Zip:** 1085

**Location 83:**

**City:** Budapest

**Country:** Hungary

**Facility:** Research Site

**Zip:** 1115

**Location 84:**

**City:** Budapest

**Country:** Hungary

**Facility:** Research Site

**Zip:** 1125

**Location 85:**

**City:** Komarom

**Country:** Hungary

**Facility:** Research Site

**Zip:** 2991

**Location 86:**

**City:** Pecs

**Country:** Hungary

**Facility:** Research Site

**Zip:** 7624

**Location 87:**

**City:** Szeged

**Country:** Hungary

**Facility:** Research Site

**Zip:** 6720

**Location 88:**

**City:** Zalaegerszeg

**Country:** Hungary

**Facility:** Research Site

**Zip:** 8900

**Location 89:**

**City:** Lyttelton

**Country:** South Africa

**Facility:** Research Site

**State:** Gauteng

**Zip:** 0140

**Location 90:**

**City:** Amanzimtoti

**Country:** South Africa

**Facility:** Research Site

**State:** KwaZulu-Natal

**Zip:** 4126

**Location 91:**

**City:** Chatsworth, Durban

**Country:** South Africa

**Facility:** Research Site

**State:** KwaZulu-Natal

**Zip:** 4092

**Location 92:**

**City:** Observatory

**Country:** South Africa

**Facility:** Research Site

**State:** Western Cape

**Zip:** 7925

**Location 93:**

**City:** Paarl

**Country:** South Africa

**Facility:** Research Site

**State:** Western Cape

**Zip:** 7646

**Location 94:**

**City:** Parow

**Country:** South Africa

**Facility:** Research Site

**State:** Western Cape

**Zip:** 7505

**Location 95:**

**City:** Somerset West

**Country:** South Africa

**Facility:** Research Site

**State:** Western Cape

**Zip:** 7130

**Location 96:**

**City:** Bloemfontein

**Country:** South Africa

**Facility:** Research Site

**Zip:** 9301

#### Overall Officials

**Official 1:**

**Affiliation:** Amgen

**Name:** MD

**Role:** STUDY_DIRECTOR

### References Module

#### References

**Citation:** Toth PP, Sattar N, Blom DJ, Martin SS, Jones SR, Monsalvo ML, Elliott M, Davis M, Somaratne R, Preiss D. Effect of Evolocumab on Lipoprotein Particles. Am J Cardiol. 2018 Feb 1;121(3):308-314. doi: 10.1016/j.amjcard.2017.10.028. Epub 2017 Nov 8.

**PMID:** 29221604

**Citation:** Blom DJ, Koren MJ, Roth E, Monsalvo ML, Djedjos CS, Nelson P, Elliott M, Wasserman SM, Ballantyne CM, Holman RR. Evaluation of the efficacy, safety and glycaemic effects of evolocumab (AMG 145) in hypercholesterolaemic patients stratified by glycaemic status and metabolic syndrome. Diabetes Obes Metab. 2017 Jan;19(1):98-107. doi: 10.1111/dom.12788. Epub 2016 Oct 14.

**PMID:** 27619750

**Citation:** Blom DJ, Djedjos CS, Monsalvo ML, Bridges I, Wasserman SM, Scott R, Roth E. Effects of Evolocumab on Vitamin E and Steroid Hormone Levels: Results From the 52-Week, Phase 3, Double-Blind, Randomized, Placebo-Controlled DESCARTES Study. Circ Res. 2015 Sep 25;117(8):731-41. doi: 10.1161/CIRCRESAHA.115.307071. Epub 2015 Jul 30.

**PMID:** 26228031

**Citation:** Blom DJ, Hala T, Bolognese M, Lillestol MJ, Toth PD, Burgess L, Ceska R, Roth E, Koren MJ, Ballantyne CM, Monsalvo ML, Tsirtsonis K, Kim JB, Scott R, Wasserman SM, Stein EA; DESCARTES Investigators. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. N Engl J Med. 2014 May 8;370(19):1809-19. doi: 10.1056/NEJMoa1316222. Epub 2014 Mar 29.

**PMID:** 24678979

**Citation:** Daviglus ML, Ferdinand KC, Lopez JAG, Wu Y, Monsalvo ML, Rodriguez CJ. Effects of Evolocumab on Low-Density Lipoprotein Cholesterol, Non-High Density Lipoprotein Cholesterol, Apolipoprotein B, and Lipoprotein(a) by Race and Ethnicity: A Meta-Analysis of Individual Participant Data From Double-Blind and Open-Label Extension Studies. J Am Heart Assoc. 2021 Jan 5;10(1):e016839. doi: 10.1161/JAHA.120.016839. Epub 2020 Dec 16.

**PMID:** 33325247

**Citation:** Kuchimanchi M, Grover A, Emery MG, Somaratne R, Wasserman SM, Gibbs JP, Doshi S. Population pharmacokinetics and exposure-response modeling and simulation for evolocumab in healthy volunteers and patients with hypercholesterolemia. J Pharmacokinet Pharmacodyn. 2018 Jun;45(3):505-522. doi: 10.1007/s10928-018-9592-y. Epub 2018 May 7.

**PMID:** 29736889

**Citation:** Kasichayanula S, Grover A, Emery MG, Gibbs MA, Somaratne R, Wasserman SM, Gibbs JP. Clinical Pharmacokinetics and Pharmacodynamics of Evolocumab, a PCSK9 Inhibitor. Clin Pharmacokinet. 2018 Jul;57(7):769-779. doi: 10.1007/s40262-017-0620-7.

**PMID:** 29353350

**Citation:** Sattar N, Toth PP, Blom DJ, Koren MJ, Soran H, Uhart M, Elliott M, Cyrille M, Somaratne R, Preiss D. Effect of the Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Evolocumab on Glycemia, Body Weight, and New-Onset Diabetes Mellitus. Am J Cardiol. 2017 Nov 1;120(9):1521-1527. doi: 10.1016/j.amjcard.2017.07.047. Epub 2017 Jul 31.

**PMID:** 28844508

**Citation:** Toth PP, Descamps O, Genest J, Sattar N, Preiss D, Dent R, Djedjos C, Wu Y, Geller M, Uhart M, Somaratne R, Wasserman SM; PROFICIO Investigators. Pooled Safety Analysis of Evolocumab in Over 6000 Patients From Double-Blind and Open-Label Extension Studies. Circulation. 2017 May 9;135(19):1819-1831. doi: 10.1161/CIRCULATIONAHA.116.025233. Epub 2017 Mar 1.

**PMID:** 28249876

**Citation:** Toth PP, Jones SR, Monsalvo ML, Elliott-Davey M, Lopez JAG, Banach M. Effect of Evolocumab on Non-High-Density Lipoprotein Cholesterol, Apolipoprotein B, and Lipoprotein(a): A Pooled Analysis of Phase 2 and Phase 3 Studies. J Am Heart Assoc. 2020 Mar 3;9(5):e014129. doi: 10.1161/JAHA.119.014129. Epub 2020 Mar 2.

**PMID:** 32114889

**Citation:** Wasserman SM, Sabatine MS, Koren MJ, Giugliano RP, Legg JC, Emery MG, Doshi S, Liu T, Somaratne R, Gibbs JP. Comparison of LDL-C Reduction Using Different Evolocumab Doses and Intervals: Biological Insights and Treatment Implications. J Cardiovasc Pharmacol Ther. 2018 Sep;23(5):423-432. doi: 10.1177/1074248418774043. Epub 2018 May 16.

**PMID:** 29768954

**Citation:** Schludi B, Giugliano RP, Sabatine MS, Raal FJ, Teramoto T, Koren MJ, Stein EA, Wang H, Monsalvo ML. Time-averaged low-density lipoprotein cholesterol lowering with evolocumab: Pooled analysis of phase 2 trials. J Clin Lipidol. 2022 Jul-Aug;16(4):538-543. doi: 10.1016/j.jacl.2022.05.069. Epub 2022 Jun 6.

**PMID:** 35760720

#### See Also Links

**Label:** AmgenTrials clinical trials website

**URL:** http://www.amgentrials.com

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000006949

- Term: Hyperlipidemias

- ID: D000050171

- Term: Dyslipidemias

- ID: D000052439

- Term: Lipid Metabolism Disorders

- ID: D000008659

- Term: Metabolic Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M9988

- Name: Hypercholesterolemia

- Relevance: HIGH

- As Found: Hypercholesterolemia

- ID: M10000

- Name: Hyperlipidemias

- Relevance: LOW

- As Found: Unknown

- ID: M10002

- Name: Hyperlipoproteinemias

- Relevance: LOW

- As Found: Unknown

- ID: M26181

- Name: Dyslipidemias

- Relevance: LOW

- As Found: Unknown

- ID: M11639

- Name: Metabolic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27029

- Name: Lipid Metabolism Disorders

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000006937

- Term: Hypercholesterolemia

### Intervention Browse Module - Ancestors

- ID: D000000924

- Term: Anticholesteremic Agents

- ID: D000000960

- Term: Hypolipidemic Agents

- ID: D000000963

- Term: Antimetabolites

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000057847

- Term: Lipid Regulating Agents

- ID: D000019161

- Term: Hydroxymethylglutaryl-CoA Reductase Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000091362

- Term: PCSK9 Inhibitors

- ID: D000015842

- Term: Serine Proteinase Inhibitors

- ID: D000011480

- Term: Protease Inhibitors

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Lipd

- Name: Lipid Regulating Agents

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: AA

- Name: Amino Acids

### Intervention Browse Module - Browse Leaves

- ID: M4225

- Name: Antibodies

- Relevance: LOW

- As Found: Unknown

- ID: M351

- Name: Atorvastatin

- Relevance: HIGH

- As Found: Of each

- ID: M10184

- Name: Immunoglobulins

- Relevance: LOW

- As Found: Unknown

- ID: M409

- Name: Ezetimibe

- Relevance: HIGH

- As Found: Amount

- ID: M348166

- Name: Evolocumab

- Relevance: HIGH

- As Found: Pragmatic

- ID: M4243

- Name: Anticholesteremic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4278

- Name: Hypolipidemic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4281

- Name: Antimetabolites

- Relevance: LOW

- As Found: Unknown

- ID: M28883

- Name: Lipid Regulating Agents

- Relevance: LOW

- As Found: Unknown

- ID: M21155

- Name: Hydroxymethylglutaryl-CoA Reductase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M2849

- Name: PCSK9 Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M14343

- Name: Protease Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M18391

- Name: Serine Proteinase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M19609

- Name: HIV Protease Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: T18

- Name: Serine

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000069059

- Term: Atorvastatin

- ID: D000069438

- Term: Ezetimibe

- ID: C000577155

- Term: Evolocumab

### Misc Info Module

#### Removed Countries

- Country: Czech Republic

- Version Holder: 2024-05-24

## Results Section

### Adverse Events Module

**Description:** Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

#### Event Groups

**Group ID:** EG000

**Title:** Placebo

**Description:** Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.

**ID:** EG000

**Other Num Affected:** 76

**Other Num at Risk:** 302

**Serious Number Affected:** 13

**Serious Number At Risk:** 302

**Title:** Placebo

**Group ID:** EG001

**Title:** Evolocumab

**Description:** Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.

**ID:** EG001

**Other Num Affected:** 177

**Other Num at Risk:** 599

**Serious Number Affected:** 33

**Serious Number At Risk:** 599

**Title:** Evolocumab

**Frequency Threshold:** 5

#### Other Events

**Term:** Influenza

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA 16.1

**Term:** Nasopharyngitis

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA 16.1

**Term:** Upper respiratory tract infection

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA 16.1

**Term:** Back pain

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Musculoskeletal and connective tissue disorders

**Source Vocabulary:** MedDRA 16.1

#### Serious Events

**Term:** Angina pectoris

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Cardiac disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num Affected:** 2

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 2

**Num At Risk:** 599

**Term:** Angina unstable

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Cardiac disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Atrial fibrillation

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Cardiac disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 302

**Group ID:** EG001

**Num At Risk:** 599

**Term:** Cardiac failure

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Cardiac disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Myocardial infarction

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Cardiac disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Palpitations

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Cardiac disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 2

**Num At Risk:** 599

**Term:** Sinus bradycardia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Cardiac disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 302

**Group ID:** EG001

**Num At Risk:** 599

**Term:** Ventricular extrasystoles

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Cardiac disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 2

**Num At Risk:** 599

**Term:** Exostosis of external ear canal

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Ear and labyrinth disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Vertigo positional

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Ear and labyrinth disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 2

**Num At Risk:** 599

**Term:** Gastritis

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Haemorrhoids

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Chest pain

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** General disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 302

**Group ID:** EG001

**Num At Risk:** 599

**Term:** Device breakage

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** General disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Non-cardiac chest pain

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** General disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Biliary tract disorder

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Hepatobiliary disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Cholelithiasis

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Hepatobiliary disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Appendicitis

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Pneumonia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Skin infection

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Joint injury

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Injury, poisoning and procedural complications

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 302

**Group ID:** EG001

**Num At Risk:** 599

**Term:** Multiple fractures

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Injury, poisoning and procedural complications

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 302

**Group ID:** EG001

**Num At Risk:** 599

**Term:** Overdose

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Injury, poisoning and procedural complications

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 302

**Group ID:** EG001

**Num At Risk:** 599

**Term:** Road traffic accident

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Injury, poisoning and procedural complications

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 302

**Group ID:** EG001

**Num At Risk:** 599

**Term:** Skull fracture

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Injury, poisoning and procedural complications

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 302

**Group ID:** EG001

**Num At Risk:** 599

**Term:** Alanine aminotransferase increased

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Investigations

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Aspartate aminotransferase increased

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Investigations

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Blood creatine phosphokinase increased

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Investigations

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Hepatic enzyme increased

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Investigations

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 302

**Group ID:** EG001

**Num At Risk:** 599

**Term:** Hypomagnesaemia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Metabolism and nutrition disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Back pain

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Musculoskeletal and connective tissue disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 2

**Num At Risk:** 599

**Term:** Intervertebral disc protrusion

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Musculoskeletal and connective tissue disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Osteoarthritis

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Musculoskeletal and connective tissue disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Spinal osteoarthritis

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Musculoskeletal and connective tissue disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 302

**Group ID:** EG001

**Num At Risk:** 599

**Term:** Breast cancer

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps)

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Ovarian cancer metastatic

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps)

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Renal neoplasm

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps)

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Uterine cancer

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps)

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Convulsion

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Nervous system disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 302

**Group ID:** EG001

**Num At Risk:** 599

**Term:** Migraine with aura

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Nervous system disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Peripheral sensory neuropathy

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Nervous system disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 302

**Group ID:** EG001

**Num At Risk:** 599

**Term:** Syncope

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Nervous system disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Ovarian cyst

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Reproductive system and breast disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Asthma

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Respiratory, thoracic and mediastinal disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Pleurisy

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Respiratory, thoracic and mediastinal disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Pulmonary embolism

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Respiratory, thoracic and mediastinal disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 2

**Num At Risk:** 599

**Term:** Breast prosthesis implantation

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Surgical and medical procedures

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Term:** Hypotension

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Vascular disorders

**Source Vocabulary:** MedDRA 16.1

##### Stats

**Group ID:** EG000

**Num At Risk:** 302

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 599

**Time Frame:** 52 weeks

## Results Section - Baseline Characteristics Module

### Denomination Counts

**Group ID:** BG000

**Value:** 303

**Group ID:** BG001

**Value:** 602

**Group ID:** BG002

**Value:** 905

**Units:** Participants

### Group

**ID:** BG000

**Title:** Placebo

**Description:** Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.

### Group

**ID:** BG001

**Title:** Evolocumab

**Description:** Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.

### Group

**ID:** BG002

**Title:** Total

**Description:** Total of all reporting groups

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 10.3

**Value:** 56.6

#### Measurement

**Group ID:** BG001

**Spread:** 10.9

**Value:** 55.9

#### Measurement

**Group ID:** BG002

**Spread:** 10.7

**Value:** 56.1

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 162

#### Measurement

**Group ID:** BG001

**Value:** 312

#### Measurement

**Group ID:** BG002

**Value:** 474

**Category Title:** Female

#### Measurement

**Group ID:** BG000

**Value:** 141

#### Measurement

**Group ID:** BG001

**Value:** 290

#### Measurement

**Group ID:** BG002

**Value:** 431

**Category Title:** Male

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 3

#### Measurement

**Group ID:** BG002

**Value:** 3

**Class Title:** American Indian or Alaska Native

#### Measurement

**Group ID:** BG000

**Value:** 16

#### Measurement

**Group ID:** BG001

**Value:** 41

#### Measurement

**Group ID:** BG002

**Value:** 57

**Class Title:** Asian

#### Measurement

**Group ID:** BG000

**Value:** 23

#### Measurement

**Group ID:** BG001

**Value:** 53

#### Measurement

**Group ID:** BG002

**Value:** 76

**Class Title:** Black or African American

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 1

#### Measurement

**Group ID:** BG002

**Value:** 1

**Class Title:** Native Hawaiian or Other Pacific Islander

#### Measurement

**Group ID:** BG000

**Value:** 249

#### Measurement

**Group ID:** BG001

**Value:** 478

#### Measurement

**Group ID:** BG002

**Value:** 727

**Class Title:** White

#### Measurement

**Group ID:** BG000

**Value:** 13

#### Measurement

**Group ID:** BG001

**Value:** 26

#### Measurement

**Group ID:** BG002

**Value:** 39

**Class Title:** Other

#### Measurement

**Group ID:** BG000

**Value:** 2

#### Measurement

**Group ID:** BG001

**Value:** 0

#### Measurement

**Group ID:** BG002

**Value:** 2

**Class Title:** Mixed Race

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 17

#### Measurement

**Group ID:** BG001

**Value:** 33

#### Measurement

**Group ID:** BG002

**Value:** 50

**Class Title:** Hispanic/Latino

#### Measurement

**Group ID:** BG000

**Value:** 286

#### Measurement

**Group ID:** BG001

**Value:** 569

#### Measurement

**Group ID:** BG002

**Value:** 855

**Class Title:** Not Hispanic/Latino

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 38

#### Measurement

**Group ID:** BG001

**Value:** 74

#### Measurement

**Group ID:** BG002

**Value:** 112

**Class Title:** Diet Only

#### Measurement

**Group ID:** BG000

**Value:** 129

#### Measurement

**Group ID:** BG001

**Value:** 256

#### Measurement

**Group ID:** BG002

**Value:** 385

**Class Title:** Diet + Atorvastatin 10 mg

#### Measurement

**Group ID:** BG000

**Value:** 73

#### Measurement

**Group ID:** BG001

**Value:** 146

#### Measurement

**Group ID:** BG002

**Value:** 219

**Class Title:** Diet + Atorvastatin 80 mg

#### Measurement

**Group ID:** BG000

**Value:** 63

#### Measurement

**Group ID:** BG001

**Value:** 126

#### Measurement

**Group ID:** BG002

**Value:** 189

**Class Title:** Diet + Atorvastatin 80 mg + Ezetimibe 10 mg

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 21.6

**Value:** 104.0

#### Measurement

**Group ID:** BG001

**Spread:** 22.1

**Value:** 104.2

#### Measurement

**Group ID:** BG002

**Spread:** 22.0

**Value:** 104.1

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 27.2

**Value:** 179.1

#### Measurement

**Group ID:** BG001

**Spread:** 27.5

**Value:** 176.8

#### Measurement

**Group ID:** BG002

**Spread:** 27.4

**Value:** 177.6

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 26.9

**Value:** 125.6

#### Measurement

**Group ID:** BG001

**Spread:** 25.6

**Value:** 124.2

#### Measurement

**Group ID:** BG002

**Spread:** 26.1

**Value:** 124.6

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 16.3

**Value:** 87.5

#### Measurement

**Group ID:** BG001

**Spread:** 16.3

**Value:** 87.0

#### Measurement

**Group ID:** BG002

**Spread:** 16.3

**Value:** 87.2

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 1.11

**Value:** 3.603

#### Measurement

**Group ID:** BG001

**Spread:** 1.04

**Value:** 3.597

#### Measurement

**Group ID:** BG002

**Spread:** 1.06

**Value:** 3.599

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 0.170

**Value:** 0.586

#### Measurement

**Group ID:** BG001

**Spread:** 0.170

**Value:** 0.593

#### Measurement

**Group ID:** BG002

**Spread:** 1.70

**Value:** 0.590

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 108.6

**Value:** 89.3

#### Measurement

**Group ID:** BG001

**Spread:** 98.5

**Value:** 84.0

#### Measurement

**Group ID:** BG002

**Spread:** 102.0

**Value:** 85.8

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 65.8

**Value:** 127.8

#### Measurement

**Group ID:** BG001

**Spread:** 63.2

**Value:** 119.8

#### Measurement

**Group ID:** BG002

**Spread:** 64.1

**Value:** 122.5

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 16.1

**Value:** 53.5

#### Measurement

**Group ID:** BG001

**Spread:** 15.5

**Value:** 52.6

#### Measurement

**Group ID:** BG002

**Spread:** 15.7

**Value:** 52.9

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 13.4

**Value:** 21.5

#### Measurement

**Group ID:** BG001

**Spread:** 11.4

**Value:** 20.0

#### Measurement

**Group ID:** BG002

**Spread:** 12.1

**Value:** 20.5

**Class Title:** 

**Denomination Units Selected:** 

## Results Section - Baseline Characteristics Module

### Measure 1
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Age, Continuous
**Unit of Measure:** years
### Measure 2
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Sex: Female, Male
**Unit of Measure:** Participants
### Measure 3
**Parameter Type:** NUMBER
**Title:** Race/Ethnicity, Customized
**Unit of Measure:** participants
### Measure 4
**Parameter Type:** NUMBER
**Title:** Race/Ethnicity, Customized
**Unit of Measure:** participants
### Measure 5
**Parameter Type:** NUMBER
**Title:** Background Therapy
**Unit of Measure:** participants
### Measure 6
**Description:** Cholesterol was measured by means of ultracentrifugation. Data are provided for the Full Analysis Set (all participants who were randomized and received at least 1 dose of study treatment).
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Low-density Lipoprotein Cholesterol (LDL-C) Concentration
**Unit of Measure:** mg/dL
### Measure 7
**Description:** Data are provided for the Full Analysis Set
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Total Cholesterol
**Unit of Measure:** mg/dL
### Measure 8
**Description:** Data are provided for the Full Analysis Set
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) Concentration
**Unit of Measure:** mg/dL
### Measure 9
**Description:** Data are provided for the Full Analysis Set
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Apolipoprotein B Concentration
**Unit of Measure:** mg/dL
### Measure 10
**Description:** Data are provided for the Full Analysis Set
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Total Cholesterol/High Density Lipoprotein-Cholesterol (HDL-C) Ratio
**Unit of Measure:** ratio
### Measure 11
**Description:** Data are provided for the Full Analysis Set
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Apolipoprotein B/Apolipoprotein A-1 Ratio
**Unit of Measure:** ratio
### Measure 12
**Description:** Data are provided for the Full Analysis Set
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Lipoprotein(a) Concentration
**Unit of Measure:** nmol/L
### Measure 13
**Description:** Data are provided for the Full Analysis Set
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Triglycerides Concentration
**Unit of Measure:** mg/dL
### Measure 14
**Description:** Data are providedfor the Full Analysis Set
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** High-density Lipoprotein Cholesterol (HDL-C) Concentration
**Unit of Measure:** mg/dL
### Measure 15
**Description:** Data are provided for the Full Analysis Set
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Very Low-density Lipoprotein Cholesterol (VLDL-C) Concentration
**Unit of Measure:** mg/dL
## Results Section - More Information Module
### Certain Agreement
**Other Details:** The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
**Restriction Type:** OTHER
**Restrictive Agreement:** True
### Point of Contact
**Organization:** Amgen Inc.
**Phone:** 866-572-6436
**Title:** Study Director
## Results Section - Outcome Measures Module
### Outcome Measure 1
#### Analysis
**CI Lower Limit:** -61.08
**CI Number of Sides:** TWO_SIDED
**CI Percentage Value:** 95
**CI Upper Limit:** -52.85
**CI Upper Limit Comment:** 
**Dispersion Type:** STANDARD_ERROR_OF_MEAN
**Dispersion Value:** 2.10
**Estimate Comment:** Treatment difference using placebo as the reference.
**Group Description:** The null hypothesis was that there was no mean difference in the percent change from Baseline at Week 52 in LDL-C between evolocumab 420 mg and placebo, and the alternative hypothesis was that a mean difference did exist.
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY
**Other Analysis Description:** 
**P-Value:** <0.001
**P-Value Comment:** 
**Parameter Type:** LS Mean Treatment Difference
**Parameter Value:** -56.97
**Statistical Comment:** The model included treatment group, stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates.
**Statistical Method:** Repeated measures linear effects model
**Tested Non-Inferiority:** 
### Outcome Measure 2
#### Analysis
**CI Lower Limit:** -62.3
**CI Number of Sides:** TWO_SIDED
**CI Percentage Value:** 95
**CI Upper Limit:** -53.3
**CI Upper Limit Comment:** 
**Dispersion Type:** STANDARD_ERROR_OF_MEAN
**Dispersion Value:** 2.3
**Estimate Comment:** Treatment difference using placebo as the reference.
**Group Description:** 
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY
**Other Analysis Description:** 
**P-Value:** <0.001
**P-Value Comment:** 
**Parameter Type:** LS Mean Treatment Difference
**Parameter Value:** -57.8
**Statistical Comment:** The model includes treatment group, stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates.
**Statistical Method:** Repeated measures linear effects model
**Tested Non-Inferiority:** 
### Outcome Measure 3
#### Analysis
**CI Lower Limit:** 70.8
**CI Number of Sides:** TWO_SIDED
**CI Percentage Value:** 95
**CI Upper Limit:** 79.7
**CI Upper Limit Comment:** 
**Dispersion Type:** 
**Dispersion Value:** 
**Estimate Comment:** Treatment difference using placebo as the reference.
**Group Description:** 
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY
**Other Analysis Description:** 
**P-Value:** <0.001
**P-Value Comment:** 
**Parameter Type:** Treatment Difference
**Parameter Value:** 75.8
**Statistical Comment:** CMH test stratified by the stratification factor. For testing, non-achievement was imputed for participants with a missing value at Week 52.
**Statistical Method:** Cochran-Mantel-Haenszel
**Tested Non-Inferiority:** 
### Outcome Measure 4
#### Analysis
**CI Lower Limit:** -60.57
**CI Number of Sides:** TWO_SIDED
**CI Percentage Value:** 95
**CI Upper Limit:** -54.45
**CI Upper Limit Comment:** 
**Dispersion Type:** STANDARD_ERROR_OF_MEAN
**Dispersion Value:** 1.56
**Estimate Comment:** Treatment difference using placebo as the reference.
**Group Description:** 
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY
**Other Analysis Description:** 
**P-Value:** <0.001
**P-Value Comment:** 
**Parameter Type:** LS Mean Treatment Difference
**Parameter Value:** -57.51
**Statistical Comment:** The model includes treatment group, stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates.
**Statistical Method:** Repeated measures linear effects model
**Tested Non-Inferiority:** 
### Outcome Measure 5
#### Analysis
**CI Lower Limit:** -37.19
**CI Number of Sides:** TWO_SIDED
**CI Percentage Value:** 95
**CI Upper Limit:** -33.11
**CI Upper Limit Comment:** 
**Dispersion Type:** STANDARD_ERROR_OF_MEAN
**Dispersion Value:** 1.04
**Estimate Comment:** Treatment difference using placebo as the reference.
**Group Description:** 
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY
**Other Analysis Description:** 
**P-Value:** <0.001
**P-Value Comment:** 
**Parameter Type:** LS Mean Treatment Difference
**Parameter Value:** -35.15
**Statistical Comment:** The model includes treatment group, stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates.
**Statistical Method:** Repeated measures linear effects model
**Tested Non-Inferiority:** 
### Outcome Measure 6
#### Analysis
**CI Lower Limit:** -36.21
**CI Number of Sides:** TWO_SIDED
**CI Percentage Value:** 95
**CI Upper Limit:** -30.68
**CI Upper Limit Comment:** 
**Dispersion Type:** STANDARD_ERROR_OF_MEAN
**Dispersion Value:** 1.41
**Estimate Comment:** Treatment difference using placebo as the reference.
**Group Description:** 
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY
**Other Analysis Description:** 
**P-Value:** <0.001
**P-Value Comment:** 
**Parameter Type:** LS Mean Treatment Difference
**Parameter Value:** -33.45
**Statistical Comment:** The model includes treatment group, stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates.
**Statistical Method:** Repeated measures linear effects model
**Tested Non-Inferiority:** 
### Outcome Measure 7
#### Analysis
**CI Lower Limit:** -54.25
**CI Number of Sides:** TWO_SIDED
**CI Percentage Value:** 95
**CI Upper Limit:** -46.28
**CI Upper Limit Comment:** 
**Dispersion Type:** STANDARD_ERROR_OF_MEAN
**Dispersion Value:** 2.03
**Estimate Comment:** Treatment difference using placebo as the reference.
**Group Description:** 
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY
**Other Analysis Description:** 
**P-Value:** <0.001
**P-Value Comment:** 
**Parameter Type:** LS Mean Treatment Difference
**Parameter Value:** -50.27
**Statistical Comment:** The model includes treatment group, stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates.
**Statistical Method:** Repeated measures linear effects model
**Tested Non-Inferiority:** 
### Outcome Measure 8
#### Analysis
**CI Lower Limit:** -47.56
**CI Number of Sides:** TWO_SIDED
**CI Percentage Value:** 95
**CI Upper Limit:** -40.85
**CI Upper Limit Comment:** 
**Dispersion Type:** STANDARD_ERROR_OF_MEAN
**Dispersion Value:** 1.71
**Estimate Comment:** Treatment difference using placebo as the reference.
**Group Description:** 
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY
**Other Analysis Description:** 
**P-Value:** <0.001
**P-Value Comment:** 
**Parameter Type:** LS Mean Treatment Difference
**Parameter Value:** -44.21
**Statistical Comment:** The model includes treatment group, stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates.
**Statistical Method:** Repeated measures linear effects model
**Tested Non-Inferiority:** 
### Outcome Measure 9
#### Analysis
**CI Lower Limit:** -40.41
**CI Number of Sides:** TWO_SIDED
**CI Percentage Value:** 95
**CI Upper Limit:** -33.87
**CI Upper Limit Comment:** 
**Dispersion Type:** STANDARD_ERROR_OF_MEAN
**Dispersion Value:** 1.67
**Estimate Comment:** Treatment difference using placebo as the reference.
**Group Description:** 
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY
**Other Analysis Description:** 
**P-Value:** <0.001
**P-Value Comment:** 
**Parameter Type:** LS Mean Treatment Difference
**Parameter Value:** -37.14
**Statistical Comment:** The model includes treatment group, stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates.
**Statistical Method:** Repeated measures linear effects model
**Tested Non-Inferiority:** 
### Outcome Measure 10
#### Analysis
**CI Lower Limit:** -49.79
**CI Number of Sides:** TWO_SIDED
**CI Percentage Value:** 95
**CI Upper Limit:** -42.63
**CI Upper Limit Comment:** 
**Dispersion Type:** STANDARD_ERROR_OF_MEAN
**Dispersion Value:** 1.82
**Estimate Comment:** Treatment difference using placebo as the reference.
**Group Description:** 
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY
**Other Analysis Description:** 
**P-Value:** <0.001
**P-Value Comment:** 
**Parameter Type:** LS Mean Treatment Difference
**Parameter Value:** -46.21
**Statistical Comment:** The model includes treatment group, stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates.
**Statistical Method:** Repeated measures linear effects model
**Tested Non-Inferiority:** 
### Outcome Measure 11
#### Analysis
**CI Lower Limit:** -26.15
**CI Number of Sides:** TWO_SIDED
**CI Percentage Value:** 95
**CI Upper Limit:** -18.55
**CI Upper Limit Comment:** 
**Dispersion Type:** STANDARD_ERROR_OF_MEAN
**Dispersion Value:** 1.94
**Estimate Comment:** Treatment difference using placebo as the reference.
**Group Description:** 
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY
**Other Analysis Description:** 
**P-Value:** <0.001
**P-Value Comment:** 
**Parameter Type:** LS Mean Treatment Difference
**Parameter Value:** -22.35
**Statistical Comment:** The model includes treatment group, stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates.
**Statistical Method:** Repeated measures linear effects model
**Tested Non-Inferiority:** 
### Outcome Measure 12
#### Analysis
**CI Lower Limit:** -17.21
**CI Number of Sides:** TWO_SIDED
**CI Percentage Value:** 95
**CI Upper Limit:** -5.86
**CI Upper Limit Comment:** 
**Dispersion Type:** STANDARD_ERROR_OF_MEAN
**Dispersion Value:** 2.89
**Estimate Comment:** Treatment difference using placebo as the reference.
**Group Description:** 
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY
**Other Analysis Description:** 
**P-Value:** <0.001
**P-Value Comment:** 
**Parameter Type:** LS Mean Treatment Difference
**Parameter Value:** -11.54
**Statistical Comment:** The model includes treatment group, stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates.
**Statistical Method:** Repeated measures linear effects model
**Tested Non-Inferiority:** 
### Outcome Measure 13
#### Analysis
**CI Lower Limit:** 3.28
**CI Number of Sides:** TWO_SIDED
**CI Percentage Value:** 95
**CI Upper Limit:** 7.56
**CI Upper Limit Comment:** 
**Dispersion Type:** STANDARD_ERROR_OF_MEAN
**Dispersion Value:** 1.09
**Estimate Comment:** Treatment difference using placebo as the reference.
**Group Description:** 
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY
**Other Analysis Description:** 
**P-Value:** <0.001
**P-Value Comment:** 
**Parameter Type:** LS Mean Treatment Difference
**Parameter Value:** 5.42
**Statistical Comment:** The model includes treatment group, stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates.
**Statistical Method:** Repeated measures linear effects model
**Tested Non-Inferiority:** 
### Outcome Measure 14
#### Analysis
**CI Lower Limit:** -40.23
**CI Number of Sides:** TWO_SIDED
**CI Percentage Value:** 95
**CI Upper Limit:** -18.08
**CI Upper Limit Comment:** 
**Dispersion Type:** STANDARD_ERROR_OF_MEAN
**Dispersion Value:** 5.64
**Estimate Comment:** Treatment difference using placebo as the reference.
**Group Description:** 
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY
**Other Analysis Description:** 
**P-Value:** <0.001
**P-Value Comment:** 
**Parameter Type:** LS Mean Treatment Difference
**Parameter Value:** -29.15
**Statistical Comment:** The model includes treatment group, stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates.
**Statistical Method:** Repeated measures linear effects model
**Tested Non-Inferiority:** 
### Outcome Measure 15
#### Analysis
**CI Lower Limit:** -3.76
**CI Number of Sides:** TWO_SIDED
**CI Percentage Value:** 95
**CI Upper Limit:** 3.48
**CI Upper Limit Comment:** 
**Dispersion Type:** STANDARD_ERROR_OF_MEAN
**Dispersion Value:** 1.84
**Estimate Comment:** Treatment difference using placebo as the reference.
**Group Description:** 
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY
**Other Analysis Description:** 
**P-Value:** 0.94
**P-Value Comment:** 
**Parameter Type:** LS Mean Treatment Difference
**Parameter Value:** -0.14
**Statistical Comment:** The ANCOVA model includes treatment group and stratification factor as covariates.
**Statistical Method:** ANCOVA
**Tested Non-Inferiority:** 
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 1.75
- **Upper Limit:** 
- **Value:** 6.83
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 1.24
- **Upper Limit:** 
- **Value:** -50.14
**Title:** 
#### Outcome Measure 2
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 1.9
- **Upper Limit:** 
- **Value:** 5.1
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 1.4
- **Upper Limit:** 
- **Value:** -52.7
**Title:** 
#### Outcome Measure 3
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 4.1
- **Spread:** 
- **Upper Limit:** 10.1
- **Value:** 6.4
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 78.8
- **Spread:** 
- **Upper Limit:** 85.3
- **Value:** 82.3
**Title:** 
#### Outcome Measure 4
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 1.31
- **Upper Limit:** 
- **Value:** 3.17
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 0.96
- **Upper Limit:** 
- **Value:** -54.35
**Title:** 
#### Outcome Measure 5
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 0.87
- **Upper Limit:** 
- **Value:** 2.85
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 0.63
- **Upper Limit:** 
- **Value:** -32.30
**Title:** 
#### Outcome Measure 6
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 1.16
- **Upper Limit:** 
- **Value:** 5.26
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 0.84
- **Upper Limit:** 
- **Value:** -28.18
**Title:** 
#### Outcome Measure 7
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 1.68
- **Upper Limit:** 
- **Value:** 8.44
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 1.21
- **Upper Limit:** 
- **Value:** -41.82
**Title:** 
#### Outcome Measure 8
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 1.41
- **Upper Limit:** 
- **Value:** 2.94
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 1.02
- **Upper Limit:** 
- **Value:** -41.26
**Title:** 
#### Outcome Measure 9
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 1.37
- **Upper Limit:** 
- **Value:** 6.47
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 0.99
- **Upper Limit:** 
- **Value:** -30.67
**Title:** 
#### Outcome Measure 10
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 1.50
- **Upper Limit:** 
- **Value:** 4.46
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 1.09
- **Upper Limit:** 
- **Value:** -41.75
**Title:** 
#### Outcome Measure 11
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 1.62
- **Upper Limit:** 
- **Value:** -5.37
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 1.19
- **Upper Limit:** 
- **Value:** -27.72
**Title:** 
#### Outcome Measure 12
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 2.39
- **Upper Limit:** 
- **Value:** 8.99
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 1.72
- **Upper Limit:** 
- **Value:** -2.55
**Title:** 
#### Outcome Measure 13
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 0.90
- **Upper Limit:** 
- **Value:** 0.35
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 0.65
- **Upper Limit:** 
- **Value:** 5.77
**Title:** 
#### Outcome Measure 14
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 4.69
- **Upper Limit:** 
- **Value:** 31.89
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 3.36
- **Upper Limit:** 
- **Value:** 2.74
**Title:** 
#### Outcome Measure 15
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 1.56
- **Upper Limit:** 
- **Value:** 2.57
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 1.14
- **Upper Limit:** 
- **Value:** 2.44
**Title:** 
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Description:** Cholesterol was measured by means of ultracentrifugation.
**Dispersion Type:** Standard Error
**Parameter Type:** LEAST_SQUARES_MEAN
**Population Description:** Full Analysis Set (all randomized subjects who received at least 1 dose of study drug).
**Reporting Status:** POSTED
**Time Frame:** Baseline and Week 52
**Title:** Percent Change From Baseline in LDL-C at Week 52
**Type:** PRIMARY
**Unit of Measure:** percent change
##### Group
**Description:** Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG000
**Title:** Placebo
##### Group
**Description:** Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG001
**Title:** Evolocumab
#### Outcome Measure 2
**Description:** Cholesterol was measured by means of ultracentrifugation.
**Dispersion Type:** Standard Error
**Parameter Type:** LEAST_SQUARES_MEAN
**Population Description:** Full Analysis Set
**Reporting Status:** POSTED
**Time Frame:** Baseline and Week 52
**Title:** Change From Baseline in LDL-C at Week 52
**Type:** SECONDARY
**Unit of Measure:** mg/dL
##### Group
**Description:** Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG000
**Title:** Placebo
##### Group
**Description:** Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG001
**Title:** Evolocumab
#### Outcome Measure 3
**Description:** An LDL-C response is defined as LDL-C level \< 70 mg/dL (1.8 mmol/L) at Week 52.
**Dispersion Type:** 95% Confidence Interval
**Parameter Type:** NUMBER
**Population Description:** Full Analysis Set
**Reporting Status:** POSTED
**Time Frame:** Week 52
**Title:** Percentage of Participants With an LDL-C Response at Week 52
**Type:** SECONDARY
**Unit of Measure:** percentage of participants
##### Group
**Description:** Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG000
**Title:** Placebo
##### Group
**Description:** Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG001
**Title:** Evolocumab
#### Outcome Measure 4
**Description:** Cholesterol was measured by means of ultracentrifugation.
**Dispersion Type:** Standard Error
**Parameter Type:** LEAST_SQUARES_MEAN
**Population Description:** Full Analysis set
**Reporting Status:** POSTED
**Time Frame:** Baseline and Week 12
**Title:** Percent Change From Baseline in LDL-C at Week 12
**Type:** SECONDARY
**Unit of Measure:** percent change
##### Group
**Description:** Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG000
**Title:** Placebo
##### Group
**Description:** Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG001
**Title:** Evolocumab
#### Outcome Measure 5
**Dispersion Type:** Standard Error
**Parameter Type:** LEAST_SQUARES_MEAN
**Population Description:** Full Analysis Set
**Reporting Status:** POSTED
**Time Frame:** Baseline and Week 12
**Title:** Percent Change From Baseline in Total Cholesterol at Week 12
**Type:** SECONDARY
**Unit of Measure:** percent change
##### Group
**Description:** Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG000
**Title:** Placebo
##### Group
**Description:** Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG001
**Title:** Evolocumab
#### Outcome Measure 6
**Dispersion Type:** Standard Error
**Parameter Type:** LEAST_SQUARES_MEAN
**Population Description:** Full Analysis Set
**Reporting Status:** POSTED
**Time Frame:** Baseline and Week 52
**Title:** Percent Change From Baseline in Total Cholesterol at Week 52
**Type:** SECONDARY
**Unit of Measure:** percent change
##### Group
**Description:** Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG000
**Title:** Placebo
##### Group
**Description:** Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG001
**Title:** Evolocumab
#### Outcome Measure 7
**Dispersion Type:** Standard Error
**Parameter Type:** LEAST_SQUARES_MEAN
**Population Description:** Full Analysis Set
**Reporting Status:** POSTED
**Time Frame:** Baseline and Week 52
**Title:** Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at Week 52
**Type:** SECONDARY
**Unit of Measure:** percent change
##### Group
**Description:** Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG000
**Title:** Placebo
##### Group
**Description:** Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG001
**Title:** Evolocumab
#### Outcome Measure 8
**Dispersion Type:** Standard Error
**Parameter Type:** LEAST_SQUARES_MEAN
**Population Description:** Full analysis set
**Reporting Status:** POSTED
**Time Frame:** Baseline and Week 52
**Title:** Percent Change From Baseline in Apolipoprotein B at Week 52
**Type:** SECONDARY
**Unit of Measure:** percent change
##### Group
**Description:** Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG000
**Title:** Placebo
##### Group
**Description:** Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG001
**Title:** Evolocumab
#### Outcome Measure 9
**Dispersion Type:** Standard Error
**Parameter Type:** LEAST_SQUARES_MEAN
**Population Description:** Full Analysis Set
**Reporting Status:** POSTED
**Time Frame:** Baseline and Week 52
**Title:** Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 52
**Type:** SECONDARY
**Unit of Measure:** percent change
##### Group
**Description:** Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG000
**Title:** Placebo
##### Group
**Description:** Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG001
**Title:** Evolocumab
#### Outcome Measure 10
**Dispersion Type:** Standard Error
**Parameter Type:** LEAST_SQUARES_MEAN
**Population Description:** Full Analysis Set
**Reporting Status:** POSTED
**Time Frame:** Baseline and Week 52
**Title:** Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 52
**Type:** SECONDARY
**Unit of Measure:** percent change
##### Group
**Description:** Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG000
**Title:** Placebo
##### Group
**Description:** Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG001
**Title:** Evolocumab
#### Outcome Measure 11
**Dispersion Type:** Standard Error
**Parameter Type:** LEAST_SQUARES_MEAN
**Population Description:** Full Analysis Set
**Reporting Status:** POSTED
**Time Frame:** Baseline and Week 52
**Title:** Percent Change From Baseline in Lipoprotein(a) at Week 52
**Type:** SECONDARY
**Unit of Measure:** percent change
##### Group
**Description:** Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG000
**Title:** Placebo
##### Group
**Description:** Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG001
**Title:** Evolocumab
#### Outcome Measure 12
**Dispersion Type:** Standard Error
**Parameter Type:** LEAST_SQUARES_MEAN
**Population Description:** Full Analysis Set
**Reporting Status:** POSTED
**Time Frame:** Baseline and Week 52
**Title:** Percent Change From Baseline in Triglycerides at Week 52
**Type:** SECONDARY
**Unit of Measure:** percent change
##### Group
**Description:** Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG000
**Title:** Placebo
##### Group
**Description:** Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG001
**Title:** Evolocumab
#### Outcome Measure 13
**Dispersion Type:** Standard Error
**Parameter Type:** LEAST_SQUARES_MEAN
**Population Description:** Full Analysis Set
**Reporting Status:** POSTED
**Time Frame:** Baseline and Week 52
**Title:** Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 52
**Type:** SECONDARY
**Unit of Measure:** percent change
##### Group
**Description:** Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG000
**Title:** Placebo
##### Group
**Description:** Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG001
**Title:** Evolocumab
#### Outcome Measure 14
**Description:** Cholesterol was measured by means of ultracentrifugation.
**Dispersion Type:** Standard Error
**Parameter Type:** LEAST_SQUARES_MEAN
**Population Description:** Full Analysis Set
**Reporting Status:** POSTED
**Time Frame:** Baseline and Week 52
**Title:** Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at Week 52
**Type:** SECONDARY
**Unit of Measure:** percent change
##### Group
**Description:** Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG000
**Title:** Placebo
##### Group
**Description:** Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG001
**Title:** Evolocumab
#### Outcome Measure 15
**Description:** Cholesterol was measured by means of ultracentrifugation.
**Dispersion Type:** Standard Error
**Parameter Type:** LEAST_SQUARES_MEAN
**Population Description:** The Effect Durability Analysis Set included participants in the FAS who adhered to the scheduled study drug and had nonmissing LDL-C values at Baseline, Week 12 and Week 52.
**Reporting Status:** POSTED
**Time Frame:** Week 12 and Week 52
**Title:** Percent Change From Week 12 to Week 52 in LDL-C
**Type:** SECONDARY
**Unit of Measure:** percent change
##### Group
**Description:** Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG000
**Title:** Placebo
##### Group
**Description:** Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** OG001
**Title:** Evolocumab
### Participant Flow Module
#### Group
**Description:** Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** FG000
**Title:** Placebo
#### Group
**Description:** Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
**ID:** FG001
**Title:** Evolocumab
#### Period
**Title:** Overall Study
##### Withdraw
**Type:** Withdrawal by Subject
###### Reason
**Group ID:** FG000
**Number of Subjects:** 9
###### Reason
**Group ID:** FG001
**Number of Subjects:** 11
##### Withdraw
**Type:** Death
###### Reason
**Group ID:** FG000
**Number of Subjects:** 0
###### Reason
**Group ID:** FG001
**Number of Subjects:** 2
##### Withdraw
**Type:** Lost to Follow-up
###### Reason
**Group ID:** FG000
**Number of Subjects:** 2
###### Reason
**Group ID:** FG001
**Number of Subjects:** 11
##### Withdraw
**Type:** Other
###### Reason
**Group ID:** FG000
**Number of Subjects:** 5
###### Reason
**Group ID:** FG001
**Number of Subjects:** 10
##### Milestone
**Type:** STARTED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 303
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 602
##### Milestone
**Type:** Received Treatment
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 302
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 599
##### Milestone
**Type:** COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 287
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 568
##### Milestone
**Type:** NOT COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 16
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 34
**Pre-Assignment Details:** Patients were assigned to 1 of 4 background lipid-lowering regimens for a 4-12 week stabilization period: diet alone, diet and 10 mg atorvastatin daily, diet and 80 mg atorvastatin daily, or diet, 80 mg atorvastatin and 10 mg ezetimibe daily. Patients meeting criteria were randomized 2:1 to evolocumab or placebo, stratified by background therapy.
**Recruitment Details:** Adults with fasting low-density lipoprotein cholesterol (LDL-C) ≥ 75 mg/dL and triglycerides ≤ 400 mg/dL were eligible. The first patient enrolled on 5 January 2012 and the last patient enrolled on 12 October 2012. All patients were counseled on the National Cholesterol Education Program Adult Treatment Panel III Therapeutic Lifestyle Changes diet.
**Has Results:** True