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Durable Effect of PCSK9 Antibody CompARed wiTh placEbo Study (DESCARTES)

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ClinicalTrials.gov Identifier: NCT01516879
Recruitment Status : Completed
First Posted : January 25, 2012
Results First Posted : September 29, 2015
Last Update Posted : June 7, 2018
Sponsor:
Information provided by (Responsible Party):
Amgen

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.

Condition or disease Intervention/treatment Phase
Hypercholesterolemia Biological: Evolocumab Biological: Placebo Drug: Atorvastatin Drug: Ezetimibe Other: Diet Only Phase 3

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 905 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : January 5, 2012
Actual Primary Completion Date : October 14, 2013
Actual Study Completion Date : October 14, 2013

Resource links provided by the National Library of Medicine

Drug Information available for: Evolocumab

Arm Intervention/treatment
Experimental: Evolocumab
Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
Biological: Evolocumab
Administered by subcutaneous injection once a month
Other Names:
  • AMG 145
  • Repatha

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

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

Other: Diet Only
Diet only, no lipid lowering background drug given

Placebo Comparator: Placebo
Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
Biological: Placebo
Administered by subcutaneous injection once a month

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

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

Other: Diet Only
Diet only, no lipid lowering background drug given




Primary Outcome Measures :
  1. Percent Change From Baseline in LDL-C at Week 52 [ Time Frame: Baseline and Week 52 ]
    Cholesterol was measured by means of ultracentrifugation.


Secondary Outcome Measures :
  1. Change From Baseline in LDL-C at Week 52 [ Time Frame: Baseline and Week 52 ]
    Cholesterol was measured by means of ultracentrifugation.

  2. Percentage of Participants With an LDL-C Response at Week 52 [ Time Frame: Week 52 ]
    An LDL-C response is defined as LDL-C level < 70 mg/dL (1.8 mmol/L) at Week 52.

  3. Percent Change From Baseline in LDL-C at Week 12 [ Time Frame: Baseline and Week 12 ]
    Cholesterol was measured by means of ultracentrifugation.

  4. Percent Change From Baseline in Total Cholesterol at Week 12 [ Time Frame: Baseline and Week 12 ]
  5. Percent Change From Baseline in Total Cholesterol at Week 52 [ Time Frame: Baseline and Week 52 ]
  6. Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at Week 52 [ Time Frame: Baseline and Week 52 ]
  7. Percent Change From Baseline in Apolipoprotein B at Week 52 [ Time Frame: Baseline and Week 52 ]
  8. Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 52 [ Time Frame: Baseline and Week 52 ]
  9. Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 52 [ Time Frame: Baseline and Week 52 ]
  10. Percent Change From Baseline in Lipoprotein(a) at Week 52 [ Time Frame: Baseline and Week 52 ]
  11. Percent Change From Baseline in Triglycerides at Week 52 [ Time Frame: Baseline and Week 52 ]
  12. Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 52 [ Time Frame: Baseline and Week 52 ]
  13. Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at Week 52 [ Time Frame: Baseline and Week 52 ]
    Cholesterol was measured by means of ultracentrifugation.

  14. Percent Change From Week 12 to Week 52 in LDL-C [ Time Frame: Week 12 and Week 52 ]
    Cholesterol was measured by means of ultracentrifugation.



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01516879


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Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen

Additional Information:
Publications:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01516879     History of Changes
Other Study ID Numbers: 20110109
First Posted: January 25, 2012    Key Record Dates
Results First Posted: September 29, 2015
Last Update Posted: June 7, 2018
Last Verified: May 2018

Keywords provided by Amgen:
Cholesterol
High Cholesterol
Elevated Cholesterol
Raised Cholesterol

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Atorvastatin Calcium
Ezetimibe
Antibodies, Monoclonal
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Immunologic Factors
Physiological Effects of Drugs