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HypercholesterolemiaPhase 3DESCARTESNCT01516879

Durable Effect of PCSK9 Antibody CompARed wiTh placEbo Study

A Phase 3 study testing Evolocumab, Atorvastatin and Ezetimibe in people with Hypercholesterolemia, run by Amgen at 96 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Hypercholesterolemia
What is being tested?
Evolocumab, Atorvastatin and Ezetimibe
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
905 participants
Where
96 sitesin 9 countries
Study dates
5 Jan 2012to 14 Oct 2013
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

96 sites in 9 countries.

96 sites in 9 countries

United States41 sites

  • Research Site

    Akron, Ohio, 44311

  • Research Site

    Anaheim, California, 92801

  • Research Site

    Atlanta, Georgia, 30338

  • Research Site

    Atlanta, Georgia, 30342

  • Research Site

    Auburn, Maine, 04210

  • Research Site

    Bethesda, Maryland, 20817

  • Research Site

    Birmingham, Alabama, 35216

  • Research Site

    Brockton, Massachusetts, 02301

  • Research Site

    Chevy Chase, Maryland, 20815

  • Research Site

    Chicago, Illinois, 60610

  • Research Site

    Cincinnati, Ohio, 45219

  • Research Site

    Cincinnati, Ohio, 45227

  • Research Site

    Cincinnati, Ohio, 45246

  • Research Site

    Columbia, Maryland, 21045

  • Research Site

    DeLand, Florida, 32720

  • Research Site

    Duncansville, Pennsylvania, 16635

  • Research Site

    Encinitas, California, 92024

  • Research Site

    Endwell, New York, 13760

  • Research Site

    Fargo, North Dakota, 58103

  • Research Site

    Houston, Texas, 77030

  • Research Site

    Indianapolis, Indiana, 46260

  • Research Site

    Jacksonville, Florida, 32204

  • Research Site

    Jacksonville, Florida, 32216

  • Research Site

    Las Vegas, Nevada, 89148

  • Research Site

    Little Rock, Arkansas, 72205

  • Research Site

    Louisville, Kentucky, 40213

  • Research Site

    Mt. Pleasant, South Carolina, 29464

  • Research Site

    New Windsor, New York, 12553

  • Research Site

    Norman, Oklahoma, 73069

  • Research Site

    Olive Branch, Mississippi, 38654

  • Research Site

    Ponte Vedra, Florida, 32081

  • Research Site

    Raleigh, North Carolina, 27609

  • Research Site

    Raleigh, North Carolina, 27612

  • Research Site

    Rapid City, South Dakota, 57702

  • Research Site

    Renton, Washington, 98057

  • Research Site

    Richmond, Virginia, 23294

  • Research Site

    Saint Paul, Minnesota, 55114

  • Research Site

    Savannah, Georgia, 31406

  • Research Site

    Seattle, Washington, 98104

  • Research Site

    Spring Valley, California, 91978

  • Research Site

    Westlake Village, California, 91361

Other trials in United States

Canada10 sites

  • Research Site

    Bay Roberts, Newfoundland and Labrador, A0A 1G0

  • Research Site

    Cambridge, Ontario, N1R 6V6

  • Research Site

    Greater Sudbury, Ontario, P3C 5K7

  • Research Site

    London, Ontario, N5W 6A2

  • Research Site

    Newmarket, Ontario, L3Y 5G8

  • Research Site

    Pointe-Claire, Quebec, H9R 3J1

  • Research Site

    Québec, Quebec, G1V 4M6

  • Research Site

    Toronto, Ontario, M9V 4B4

  • Research Site

    Toronto, Ontario, M9W 4L6

  • Research Site

    Victoria, British Columbia, V8T 5G4

Other trials in Canada

Czechia10 sites

  • Research Site

    Brno, 602 00

  • Research Site

    Brno, 625 00

  • Research Site

    Chomutov, 430 02

  • Research Site

    Hradec Králové, 500 05

  • Research Site

    Pardubice, 530 02

  • Research Site

    Pilsen, 305 99

  • Research Site

    Prague, 120 00

  • Research Site

    Prague, 140 21

  • Research Site

    Prague, 150 06

  • Research Site

    Slaný, 274 01

Other trials in Czechia

Hungary8 sites

  • Research Site

    Baja, 6500

  • Research Site

    Budapest, 1085

  • Research Site

    Budapest, 1115

  • Research Site

    Budapest, 1125

  • Research Site

    Komárom, 2991

  • Research Site

    Pécs, 7624

  • Research Site

    Szeged, 6720

  • Research Site

    Zalaegerszeg, 8900

Other trials in Hungary

South Africa8 sites

  • Research Site

    Bloemfontein, 9301

  • Research Site

    Chatsworth, Durban, KwaZulu-Natal, 4092

  • Research Site

    eManzimtoti, KwaZulu-Natal, 4126

  • Research Site

    Lyttelton, Gauteng, 0140

  • Research Site

    Observatory, Western Cape, 7925

  • Research Site

    Paarl, Western Cape, 7646

  • Research Site

    Parow, Western Cape, 7505

  • Research Site

    Somerset West, Western Cape, 7130

Other trials in South Africa

Australia6 sites

  • Research Site

    Camperdown, New South Wales, 2015

  • Research Site

    Carina Heights, Queensland, 4152

  • Research Site

    Fitzroy, Victoria, 3065

  • Research Site

    Maroubra, New South Wales, 2035

  • Research Site

    Milton, Queensland, 4064

  • Research Site

    Perth, Western Australia, 6000

Other trials in Australia

Belgium6 sites

  • Research Site

    Anthée, 5520

  • Research Site

    Brussels, 1200

  • Research Site

    Ghent, 9000

  • Research Site

    Gozée, 6534

  • Research Site

    Ham, 3945

  • Research Site

    Ostend, 8400

Other trials in Belgium

Austria4 sites

  • Research Site

    Feldkirch, 6807

  • Research Site

    Innsbruck, 6020

  • Research Site

    Salzburg, 5020

  • Research Site

    Wels, 4600

Other trials in Austria

Denmark3 sites

  • Research Site

    Aalborg, 9000

  • Research Site

    Ballerup Municipality, 2750

  • Research Site

    Vejle, 7100

Other trials in Denmark

About this 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

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.

Read the 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.

Being tested
Evolocumab, Placebo, Atorvastatin, Ezetimibe, Diet Only
Keywords
Cholesterol, High Cholesterol, Elevated Cholesterol, Raised Cholesterol
Medical subject headings
Hypercholesterolemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EvolocumabBiological

    Also called AMG 145, Repatha

    Administered by subcutaneous injection once a month

  • PlaceboBiological

    Administered by subcutaneous injection once a month

  • AtorvastatinDrug

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

  • EzetimibeDrug

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

  • Diet OnlyOther

    Diet only, no lipid lowering background drug given

Study groups in NCT01516879
Study groupRoleWhat they receive
EvolocumabExperimentalParticipants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
Receives: Biological: Evolocumab; Drug: Atorvastatin; Drug: Ezetimibe; Other: Diet Only
PlaceboPlacebo comparatorParticipants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
Receives: Biological: Placebo; Drug: Atorvastatin; Drug: Ezetimibe; Other: Diet Only

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percent Change From Baseline in LDL-C at Week 52

    Cholesterol was measured by means of ultracentrifugation.

    Measured: Baseline and Week 52

Secondary outcomes (14)

  1. Change From Baseline in LDL-C at Week 52

    Cholesterol was measured by means of ultracentrifugation.

    Measured: Baseline and Week 52

  2. Percentage of Participants With an LDL-C Response at Week 52

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

    Measured: Week 52

  3. Percent Change From Baseline in LDL-C at Week 12

    Cholesterol was measured by means of ultracentrifugation.

    Measured: Baseline and Week 12

  4. Percent Change From Baseline in Total Cholesterol at Week 12

    Measured: Baseline and Week 12

  5. Percent Change From Baseline in Total Cholesterol at Week 52

    Measured: Baseline and Week 52

  6. Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at Week 52

    Measured: Baseline and Week 52

  7. Percent Change From Baseline in Apolipoprotein B at Week 52

    Measured: Baseline and Week 52

  8. Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 52

    Measured: Baseline and Week 52

  9. Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 52

    Measured: Baseline and Week 52

  10. Percent Change From Baseline in Lipoprotein(a) at Week 52

    Measured: Baseline and Week 52

  11. Percent Change From Baseline in Triglycerides at Week 52

    Measured: Baseline and Week 52

  12. Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 52

    Measured: Baseline and Week 52

  13. Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at Week 52

    Cholesterol was measured by means of ultracentrifugation.

    Measured: Baseline and Week 52

  14. Percent Change From Week 12 to Week 52 in LDL-C

    Cholesterol was measured by means of ultracentrifugation.

    Measured: Week 12 and Week 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jan 2012 (estimated)
  2. Study start5 Jan 2012
  3. Primary completion14 Oct 2013
  4. Study completion14 Oct 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
905 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01516879
Sponsor's protocol ID
20110109
Acronym
DESCARTES
Status last verified
Jul 2022
First submitted
18 Jan 2012
Last updated
22 Jul 2022
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 29221604

  • 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.

    PubMed 27619750

  • 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.

    PubMed 26228031

  • 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.

    PubMed 24678979

  • 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.

    PubMed 33325247

  • 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.

    PubMed 29736889

  • 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.

    PubMed 29353350

  • 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.

    PubMed 28844508

  • 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.

    PubMed 28249876

  • 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.

    PubMed 32114889

  • 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.

    PubMed 29768954

  • 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.

    PubMed 35760720

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Evolocumab, Atorvastatin and Ezetimibe in people with Hypercholesterolemia, run by Amgen at 96 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 96 sites in United States, Canada, Czechia, Hungary, South Africa and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Sep 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline in LDL-C at Week 52 (time frame: Baseline and Week 52). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01516879, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2022.

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