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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01516879
First received: January 18, 2012
Last updated: August 28, 2015
Last verified: August 2015
  Purpose
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 Intervention Phase
Hypercholesterolemia
Biological: Evolocumab
Biological: Placebo
Drug: Atorvastatin
Drug: Ezetimibe
Other: Diet Only
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Percent Change From Baseline in LDL-C at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    Cholesterol was measured by means of ultracentrifugation.


Secondary Outcome Measures:
  • Change From Baseline in LDL-C at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    Cholesterol was measured by means of ultracentrifugation.

  • Percentage of Participants With an LDL-C Response at Week 52 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    An LDL-C response is defined as LDL-C level < 70 mg/dL (1.8 mmol/L) at Week 52.

  • Percent Change From Baseline in LDL-C at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Cholesterol was measured by means of ultracentrifugation.

  • Percent Change From Baseline in Total Cholesterol at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Total Cholesterol at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Apolipoprotein B at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Lipoprotein(a) at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Triglycerides at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    Cholesterol was measured by means of ultracentrifugation.

  • Percent Change From Week 12 to Week 52 in LDL-C [ Time Frame: Week 12 and Week 52 ] [ Designated as safety issue: No ]
    Cholesterol was measured by means of ultracentrifugation.


Enrollment: 905
Study Start Date: January 2012
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Genders Eligible for Study:   Both
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01516879

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United States, Alabama
Research Site
Birmingham, Alabama, United States, 35216
United States, Arkansas
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Little Rock, Arkansas, United States, 72205
United States, California
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Anaheim, California, United States, 92801
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Encinitas, California, United States, 92024
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Spring Valley, California, United States, 91978
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Westlake Village, California, United States, 91361
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DeLand, Florida, United States, 32720
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Jacksonville, Florida, United States, 32216
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Ponte Vedra, Florida, United States, 32081
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Atlanta, Georgia, United States, 30338
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Las Vegas, Nevada, United States, 89148
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Fitzroy, Victoria, Australia, 3065
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Perth, Western Australia, Australia, 6000
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Feldkirch, Austria, 6807
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Plzen, Czech Republic, 305 99
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Slany, Czech Republic, 274 01
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Aalborg, Denmark, 9000
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Ballerup, Denmark, 2750
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Vejle, Denmark, 7100
Hungary
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Baja, Hungary, 6500
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Budapest, Hungary, 1085
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Budapest, Hungary, 1115
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Budapest, Hungary, 1125
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Komarom, Hungary, 2991
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Pecs, Hungary, 7624
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Szeged, Hungary, 6720
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Zalaegerszeg, Hungary, 8900
South Africa
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Lyttelton, Gauteng, South Africa, 0140
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Amanzimtoti, KwaZulu-Natal, South Africa, 4126
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Chatsworth, Durban, KwaZulu-Natal, South Africa, 4092
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Observatory, Western Cape, South Africa, 7925
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Paarl, Western Cape, South Africa, 7646
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Parow, Western Cape, South Africa, 7505
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Somerset West, Western Cape, South Africa, 7130
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Bloemfontein, South Africa, 9301
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01516879     History of Changes
Other Study ID Numbers: 20110109 
Study First Received: January 18, 2012
Results First Received: August 28, 2015
Last Updated: August 28, 2015
Health Authority: United States: Food and Drug Administration
Austria: Agency for Health and Food Safety
Canada: Health Canada
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Denmark: Danish Medicines Agency
South Africa: Medicines Control Council
Hungary: National Institute of Pharmacy
Australia: Department of Health and Ageing Therapeutic Goods Administration

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
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 24, 2016