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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01516879




Registration number
NCT01516879
Ethics application status
Date submitted
18/01/2012
Date registered
25/01/2012
Date last updated
22/07/2022

Titles & IDs
Public title
Durable Effect of PCSK9 Antibody CompARed wiTh placEbo Study
Scientific 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
Secondary ID [1] 0 0
20110109
Universal Trial Number (UTN)
Trial acronym
DESCARTES
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypercholesterolemia 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Evolocumab
Treatment: Other - Placebo
Treatment: Drugs - Atorvastatin
Treatment: Drugs - Ezetimibe
Other interventions - Diet Only

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

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


Treatment: Other: Evolocumab
Administered by subcutaneous injection once a month

Treatment: Other: Placebo
Administered by subcutaneous injection once a month

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

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

Other interventions: Diet Only
Diet only, no lipid lowering background drug given
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent Change From Baseline in LDL-C at Week 52
Timepoint [1] 0 0
Baseline and Week 52
Secondary outcome [1] 0 0
Change From Baseline in LDL-C at Week 52
Timepoint [1] 0 0
Baseline and Week 52
Secondary outcome [2] 0 0
Percentage of Participants With an LDL-C Response at Week 52
Timepoint [2] 0 0
Week 52
Secondary outcome [3] 0 0
Percent Change From Baseline in LDL-C at Week 12
Timepoint [3] 0 0
Baseline and Week 12
Secondary outcome [4] 0 0
Percent Change From Baseline in Total Cholesterol at Week 12
Timepoint [4] 0 0
Baseline and Week 12
Secondary outcome [5] 0 0
Percent Change From Baseline in Total Cholesterol at Week 52
Timepoint [5] 0 0
Baseline and Week 52
Secondary outcome [6] 0 0
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at Week 52
Timepoint [6] 0 0
Baseline and Week 52
Secondary outcome [7] 0 0
Percent Change From Baseline in Apolipoprotein B at Week 52
Timepoint [7] 0 0
Baseline and Week 52
Secondary outcome [8] 0 0
Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 52
Timepoint [8] 0 0
Baseline and Week 52
Secondary outcome [9] 0 0
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 52
Timepoint [9] 0 0
Baseline and Week 52
Secondary outcome [10] 0 0
Percent Change From Baseline in Lipoprotein(a) at Week 52
Timepoint [10] 0 0
Baseline and Week 52
Secondary outcome [11] 0 0
Percent Change From Baseline in Triglycerides at Week 52
Timepoint [11] 0 0
Baseline and Week 52
Secondary outcome [12] 0 0
Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 52
Timepoint [12] 0 0
Baseline and Week 52
Secondary outcome [13] 0 0
Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at Week 52
Timepoint [13] 0 0
Baseline and Week 52
Secondary outcome [14] 0 0
Percent Change From Week 12 to Week 52 in LDL-C
Timepoint [14] 0 0
Week 12 and Week 52

Eligibility
Key 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
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/01/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
14/10/2013
Sample size
Target
Accrual to date
Final
905
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Research Site - Camperdown
Recruitment hospital [2] 0 0
Research Site - Maroubra
Recruitment hospital [3] 0 0
Research Site - Carina Heights
Recruitment hospital [4] 0 0
Research Site - Milton
Recruitment hospital [5] 0 0
Research Site - Fitzroy
Recruitment hospital [6] 0 0
Research Site - Perth
Recruitment postcode(s) [1] 0 0
2015 - Camperdown
Recruitment postcode(s) [2] 0 0
2035 - Maroubra
Recruitment postcode(s) [3] 0 0
4152 - Carina Heights
Recruitment postcode(s) [4] 0 0
4064 - Milton
Recruitment postcode(s) [5] 0 0
3065 - Fitzroy
Recruitment postcode(s) [6] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
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Arkansas
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United States of America
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California
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Florida
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Georgia
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Illinois
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Indiana
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Kentucky
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Maine
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Maryland
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Massachusetts
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Minnesota
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Mississippi
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Nevada
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New York
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North Carolina
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North Dakota
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Ohio
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Oklahoma
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Texas
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Virginia
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Washington
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Austria
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Feldkirch
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Austria
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Innsbruck
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Austria
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Salzburg
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Austria
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Wels
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Belgium
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Anthée
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Belgium
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Bruxelles
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Belgium
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Gent
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Belgium
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Gozee
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Belgium
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Ham
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Oostende
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Brno
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Chomutov
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Czechia
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Hradec Kralove
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Czechia
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Pardubice
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Czechia
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Plzen
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Czechia
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Praha 2
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Czechia
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Czechia
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Slany
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Aalborg
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Ballerup
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Vejle
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Hungary
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Baja
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Budapest
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Komarom
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Hungary
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Pecs
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Hungary
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Szeged
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Hungary
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Zalaegerszeg
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South Africa
State/province [58] 0 0
Gauteng
Country [59] 0 0
South Africa
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KwaZulu-Natal
Country [60] 0 0
South Africa
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Western Cape
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South Africa
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Bloemfontein

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01516879
Trial related presentations / 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01516879