Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects -2

NCT ID: NCT01763905

Last Updated: 2020-07-20

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

307 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-01-24

Study Completion Date

2013-11-19

Brief Summary

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The primary objective was to evaluate the effect of 12 weeks of subcutaneous (SC) evolocumab every 2 weeks (Q2W) and monthly (QM), compared with ezetimibe, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic adults unable to tolerate an effective dose of a statin (HMG-CoA (5-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors).

Detailed Description

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Conditions

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Hyperlipidemia

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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Ezetimibe (Q2W)

Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.

Group Type ACTIVE_COMPARATOR

Placebo to Evolocumab

Intervention Type DRUG

Subcutaneous injection

Ezetimibe

Intervention Type DRUG

Tablet for oral administration

Ezetimibe (QM)

Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.

Group Type ACTIVE_COMPARATOR

Placebo to Evolocumab

Intervention Type DRUG

Subcutaneous injection

Ezetimibe

Intervention Type DRUG

Tablet for oral administration

Evolocumab Q2W

Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.

Group Type EXPERIMENTAL

Evolocumab

Intervention Type BIOLOGICAL

Subcutaneous injection

Placebo to Ezetimibe

Intervention Type DRUG

Tablet for oral administration

Evolocumab QM

Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.

Group Type EXPERIMENTAL

Evolocumab

Intervention Type BIOLOGICAL

Subcutaneous injection

Placebo to Ezetimibe

Intervention Type DRUG

Tablet for oral administration

Interventions

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Evolocumab

Subcutaneous injection

Intervention Type BIOLOGICAL

Placebo to Evolocumab

Subcutaneous injection

Intervention Type DRUG

Ezetimibe

Tablet for oral administration

Intervention Type DRUG

Placebo to Ezetimibe

Tablet for oral administration

Intervention Type DRUG

Other Intervention Names

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AMG 145 Repatha Zetia

Eligibility Criteria

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Inclusion Criteria

* Male or female ≥ 18 to ≤ 80 years of age
* Not on a statin or on a low dose statin with stable dose for at least 4 weeks
* History of intolerance to at least 2 statins
* Subject not at LDL-C goal
* Lipid lowering therapy has been stable prior to enrolment for at least 4 weeks.
* Fasting triglycerides ≤ 400 mg/dL

Exclusion Criteria

* New York Heart Association (NYHA) III or IV heart failure
* Uncontrolled cardiac arrhythmia
* Uncontrolled hypertension
* Type 1 diabetes, poorly controlled type 2 diabetes
* Uncontrolled hypothyroidism or hyperthyroidism
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

Carmichael, California, United States

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Los Angeles, California, United States

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Mission Viejo, California, United States

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Thousand Oaks, California, 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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Auburn, Maine, United States

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Traverse City, Michigan, United States

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St Louis, Missouri, United States

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Henderson, Nevada, United States

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Las Vegas, Nevada, United States

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Las Vegas, Nevada, United States

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New York, New York, United States

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Raleigh, North Carolina, United States

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Akron, Ohio, United States

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Cincinnati, Ohio, United States

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Cleveland, Ohio, United States

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Norman, Oklahoma, United States

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Houston, Texas, United States

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Camperdown, New South Wales, Australia

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Milton, Queensland, Australia

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Melbourne, Victoria, Australia

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Perth, Western Australia, Australia

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Brussels, , Belgium

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Ghent, , Belgium

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La Louvière, , Belgium

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Newmarket, Ontario, Canada

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Lachine, Quebec, Canada

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Pointe-Claire, Quebec, Canada

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Aalborg, , Denmark

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Ballerup Municipality, , Denmark

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Vejle, , Denmark

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Lille, , France

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Paris, , France

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Vénissieux, , France

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Bad Krozingen, , Germany

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Dresden, , Germany

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Heppenheim an der Bergstrasse, , Germany

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Hong Kong, , Hong Kong

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New Territories, , Hong Kong

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Alkmaar, , Netherlands

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Amsterdam, , Netherlands

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Groningen, , Netherlands

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Lodz, , Poland

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Warsaw, , Poland

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Midrand, Gauteng, South Africa

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Observatory, Western Cape, South Africa

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Somerset West, Western Cape, South Africa

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Córdoba, Andalusia, Spain

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Zaragoza, Aragon, Spain

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Reus, Catalonia, Spain

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Lugano, , Switzerland

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Reinach, , Switzerland

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Liverpool, , United Kingdom

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London, , United Kingdom

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Telford, , United Kingdom

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West Bromwich, , United Kingdom

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Countries

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United States Australia Belgium Canada Denmark France Germany Hong Kong Netherlands Poland South Africa Spain Switzerland United Kingdom

References

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Stroes E, Robinson JG, Raal FJ, Dufour R, Sullivan D, Kassahun H, Ma Y, Wasserman SM, Koren MJ. Consistent LDL-C response with evolocumab among patient subgroups in PROFICIO: A pooled analysis of 3146 patients from phase 3 studies. Clin Cardiol. 2018 Oct;41(10):1328-1335. doi: 10.1002/clc.23049. Epub 2018 Oct 21.

Reference Type BACKGROUND
PMID: 30120772 (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)

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)

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)

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

Reference Type BACKGROUND
PMID: 30073585 (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)

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)

Cho L, Rocco M, Colquhoun D, Sullivan D, Rosenson RS, Dent R, Xue A, Scott R, Wasserman SM, Stroes E. Design and rationale of the GAUSS-2 study trial: a double-blind, ezetimibe-controlled phase 3 study of the efficacy and tolerability of evolocumab (AMG 145) in subjects with hypercholesterolemia who are intolerant of statin therapy. Clin Cardiol. 2014 Mar;37(3):131-9. doi: 10.1002/clc.22248. Epub 2014 Jan 29.

Reference Type BACKGROUND
PMID: 24477778 (View on PubMed)

Stroes E, Colquhoun D, Sullivan D, Civeira F, Rosenson RS, Watts GF, Bruckert E, Cho L, Dent R, Knusel B, Xue A, Scott R, Wasserman SM, Rocco M; GAUSS-2 Investigators. Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab. J Am Coll Cardiol. 2014 Jun 17;63(23):2541-2548. doi: 10.1016/j.jacc.2014.03.019. Epub 2014 Mar 30.

Reference Type BACKGROUND
PMID: 24694531 (View on PubMed)

Shapiro MD, Minnier J, Tavori H, Kassahun H, Flower A, Somaratne R, Fazio S. Relationship Between Low-Density Lipoprotein Cholesterol and Lipoprotein(a) Lowering in Response to PCSK9 Inhibition With Evolocumab. J Am Heart Assoc. 2019 Feb 19;8(4):e010932. doi: 10.1161/JAHA.118.010932.

Reference Type BACKGROUND
PMID: 30755061 (View on PubMed)

Koren MJ, Jones PH, Robinson JG, Sullivan D, Cho L, Hucko T, Lopez JAG, Fleishman AN, Somaratne R, Stroes E. A Comparison of Ezetimibe and Evolocumab for Atherogenic Lipid Reduction in Four Patient Populations: A Pooled Efficacy and Safety Analysis of Three Phase 3 Studies. Cardiol Ther. 2020 Dec;9(2):447-465. doi: 10.1007/s40119-020-00181-8. Epub 2020 Jun 20.

Reference Type BACKGROUND
PMID: 32564340 (View on PubMed)

Related Links

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http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

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2012-001364-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

20110116

Identifier Type: -

Identifier Source: org_study_id

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