Durable Effect of PCSK9 Antibody CompARed wiTh placEbo Study

NCT ID: NCT01516879

Last Updated: 2022-07-22

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

905 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-01-05

Study Completion Date

2013-10-14

Brief Summary

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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

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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

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Hypercholesterolemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Evolocumab

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

Group Type EXPERIMENTAL

Evolocumab

Intervention Type BIOLOGICAL

Administered by subcutaneous injection once a month

Atorvastatin

Intervention Type DRUG

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

Ezetimibe

Intervention Type DRUG

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

Diet Only

Intervention Type OTHER

Diet only, no lipid lowering background drug given

Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

Administered by subcutaneous injection once a month

Atorvastatin

Intervention Type DRUG

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

Ezetimibe

Intervention Type DRUG

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

Diet Only

Intervention Type OTHER

Diet only, no lipid lowering background drug given

Interventions

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Evolocumab

Administered by subcutaneous injection once a month

Intervention Type BIOLOGICAL

Placebo

Administered by subcutaneous injection once a month

Intervention Type BIOLOGICAL

Atorvastatin

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

Intervention Type DRUG

Ezetimibe

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

Intervention Type DRUG

Diet Only

Diet only, no lipid lowering background drug given

Intervention Type OTHER

Other Intervention Names

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AMG 145 Repatha

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MD

Role: STUDY_DIRECTOR

Amgen

Locations

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Research Site

Birmingham, Alabama, United States

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Little Rock, Arkansas, United States

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Anaheim, California, United States

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Encinitas, California, United States

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Spring Valley, California, United States

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Westlake Village, California, United States

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DeLand, Florida, United States

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Jacksonville, Florida, United States

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Jacksonville, Florida, United States

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Ponte Vedra, Florida, United States

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Atlanta, Georgia, United States

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Atlanta, Georgia, United States

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Savannah, Georgia, United States

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Chicago, Illinois, United States

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Indianapolis, Indiana, United States

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Louisville, Kentucky, United States

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Auburn, Maine, United States

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Bethesda, Maryland, United States

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Chevy Chase, Maryland, United States

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Columbia, Maryland, United States

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Brockton, Massachusetts, United States

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Saint Paul, Minnesota, United States

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Olive Branch, Mississippi, United States

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Las Vegas, Nevada, United States

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Endwell, New York, United States

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New Windsor, New York, United States

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Raleigh, North Carolina, United States

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Raleigh, North Carolina, United States

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Fargo, North Dakota, United States

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Akron, Ohio, United States

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Cincinnati, Ohio, United States

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Cincinnati, Ohio, United States

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Cincinnati, Ohio, United States

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Norman, Oklahoma, United States

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Duncansville, Pennsylvania, United States

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Mt. Pleasant, South Carolina, United States

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Rapid City, South Dakota, United States

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Houston, Texas, United States

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Richmond, Virginia, United States

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Renton, Washington, United States

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Seattle, Washington, United States

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Camperdown, New South Wales, Australia

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Maroubra, New South Wales, Australia

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Carina Heights, Queensland, Australia

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Milton, Queensland, Australia

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Fitzroy, Victoria, Australia

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Perth, Western Australia, Australia

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Feldkirch, , Austria

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Innsbruck, , Austria

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Salzburg, , Austria

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Wels, , Austria

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Anthée, , Belgium

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Brussels, , Belgium

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Ghent, , Belgium

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Gozée, , Belgium

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Ham, , Belgium

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Ostend, , Belgium

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Victoria, British Columbia, Canada

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Bay Roberts, Newfoundland and Labrador, Canada

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Cambridge, Ontario, Canada

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Greater Sudbury, Ontario, Canada

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London, Ontario, Canada

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Newmarket, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Pointe-Claire, Quebec, Canada

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Québec, Quebec, Canada

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Brno, , Czechia

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Brno, , Czechia

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Chomutov, , Czechia

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Hradec Králové, , Czechia

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Pardubice, , Czechia

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Pilsen, , Czechia

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Prague, , Czechia

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Prague, , Czechia

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Prague, , Czechia

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Slaný, , Czechia

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Aalborg, , Denmark

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Ballerup Municipality, , Denmark

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Vejle, , Denmark

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Baja, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Komárom, , Hungary

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Pécs, , Hungary

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Szeged, , Hungary

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Zalaegerszeg, , Hungary

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Lyttelton, Gauteng, South Africa

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Chatsworth, Durban, KwaZulu-Natal, South Africa

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eManzimtoti, KwaZulu-Natal, South Africa

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Observatory, Western Cape, South Africa

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Paarl, Western Cape, South Africa

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Parow, Western Cape, South Africa

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Somerset West, Western Cape, South Africa

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Bloemfontein, , South Africa

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Countries

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United States Australia Austria Belgium Canada Czechia Denmark Hungary South Africa

References

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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.

Reference Type BACKGROUND
PMID: 29221604 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27619750 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26228031 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24678979 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33325247 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29736889 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29353350 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28844508 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28249876 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32114889 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29768954 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35760720 (View on PubMed)

Related Links

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http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

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20110109

Identifier Type: -

Identifier Source: org_study_id

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