Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy for Easing Lipid Levels-2 (MENDEL-2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01763827
First received: January 7, 2013
Last updated: May 29, 2014
Last verified: May 2014
  Purpose

The primary hypothesis is that dosing regimens of monotherapy Evolocumab(AMG 145) will be well tolerated and will result in greater reduction of Low Density Lipoprotein -Cholesterol, than placebo and ezetimibe in subjects with a 10-year Framingham risk score of 10% or less.


Condition Intervention Phase
Hyperlipidemia
Biological: Evolocumab (AMG 145)
Drug: Ezetimibe
Other: Placebo (administered subcutaneously)
Other: Placebo (administered orally)
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 and Ezetimibe-controlled, Multicenter Study to Evaluate Safety and Efficacy of Lipid Lowering Monotherapy With Evolocumab(AMG 145) in Subjects With a 10-Year Framingham Risk Score of 10% or Less

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Mean percent change from baseline in low density lipoprotein-cholesterol [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in low density lipoprotein-cholesterol

  • Percent change from baseline in low density lipoprotein-cholesterol [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in low density lipoprotein-cholesterol


Secondary Outcome Measures:
  • Mean change from baseline in low density lipoprotein-cholesterol [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean change from baseline in low density lipoprotein-cholesterol

  • Change from baseline in low density lipoprotein-cholesterol [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Change from baseline in low density lipoprotein-cholesterol

  • Mean low density lipoprotein-cholesterol response (low density lipoprotein-cholesterol < 70 mg/dL [1.8 mmol/L]) [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean low density lipoprotein-cholesterol response (low density lipoprotein-cholesterol < 70 mg/dL [1.8 mmol/L])

  • Low density lipoprotein-cholesterol response (low density lipoprotein-cholesterol < 70 mg/dL [1.8 mmol/L]) [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Low density lipoprotein-cholesterol response (low density lipoprotein-cholesterol < 70 mg/dL [1.8 mmol/L])

  • Mean percent change from baseline in non-high density lipoprotein-cholesterol [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in non-high density lipoprotein-cholesterol

  • Percent change from baseline in non-high density lipoprotein-cholesterol [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in non-high density lipoprotein-cholesterol

  • Mean percent change from baseline in apolipoprotein B [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in apolipoprotein B

  • Percent change from baseline in apolipoprotein B [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in apolipoprotein B

  • Mean percent change from baseline in the total cholesterol/high density lipoprotein-cholesterol ratio [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in the total cholesterol/high density lipoprotein-cholesterol ratio

  • Percent change from baseline in the total cholesterol/high density lipoprotein-cholesterol ratio [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in the total cholesterol/high density lipoprotein-cholesterol ratio

  • Mean percent change from baseline in apolipoprotein B/apolipoprotein A1 ratio [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in apolipoprotein B/apolipoprotein A1 ratio

  • Percent change from baseline in apolipoprotein B/apolipoprotein A1 ratio [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in apolipoprotein B/apolipoprotein A1 ratio

  • Mean percent change from baseline in lipoprotein (a) [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in lipoprotein (a)

  • Percent change from baseline in lipoprotein (a) [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in lipoprotein (a)

  • Mean percent change from baseline in triglycerides [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in triglycerides

  • Percent change from baseline in triglycerides [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in triglycerides

  • Mean percent change from baseline in high density lipoprotein-cholesterol [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in high density lipoprotein-cholesterol

  • Percent change from baseline in high density lipoprotein-cholesterol [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in high density lipoprotein-cholesterol

  • Mean percent change from baseline in very low density lipoprotein-cholesterol [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in very low density lipoprotein-cholesterol

  • Percent change from baseline in very low density lipoprotein-cholesterol [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in very low density lipoprotein-cholesterol


Enrollment: 614
Study Start Date: January 2013
Study Completion Date: December 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Dose 1 of subcutaneous Evolocumab (AMG 145) every 2 weeks and placebo orally/daily
Biological: Evolocumab (AMG 145)
Subject will receive Evolocumab (AMG 145) every 2 weeks or monthly
Other: Placebo (administered orally)
Subject will receive Placebo daily
Experimental: Arm 2
Dose 2 of subcutaneous Evolocumab (AMG 145) monthly and placebo orally/daily
Biological: Evolocumab (AMG 145)
Subject will receive Evolocumab (AMG 145) every 2 weeks or monthly
Other: Placebo (administered orally)
Subject will receive Placebo daily
Active Comparator: Arm 3
Dose 3 of subcutaneous placebo every 2 weeks and Ezetimibe orally/daily
Drug: Ezetimibe
Subject will receive Ezetimibe daily
Other: Placebo (administered subcutaneously)
Subject will receive Placebo every 2 weeks or monthly. All patients at screening will participate in the placebo run-in.
Active Comparator: Arm 4
Dose 4 of subcutaneous placebo monthly and Ezetimibe orally/daily
Drug: Ezetimibe
Subject will receive Ezetimibe daily
Other: Placebo (administered subcutaneously)
Subject will receive Placebo every 2 weeks or monthly. All patients at screening will participate in the placebo run-in.
Placebo Comparator: Arm 5
Dose 5 of subcutaneous placebo every 2 weeks and placebo orally/daily
Other: Placebo (administered subcutaneously)
Subject will receive Placebo every 2 weeks or monthly. All patients at screening will participate in the placebo run-in.
Other: Placebo (administered orally)
Subject will receive Placebo daily
Placebo Comparator: Arm 6
Dose 6 of subcutaneous placebo monthly and placebo orally/daily
Other: Placebo (administered subcutaneously)
Subject will receive Placebo every 2 weeks or monthly. All patients at screening will participate in the placebo run-in.
Other: Placebo (administered orally)
Subject will receive Placebo daily

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female ≥ 18 to ≤ 80 years of age
  • NCEP ATP III Framingham risk score of 10% or less
  • Fasting LDL-C ≥ 100 mg/dL (2.6 mmol/L) and <190mg/dL
  • Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L)

Exclusion Criteria:

  • History of coronary heart disease
  • NYHA III or IV heart failure
  • Uncontrolled cardiac arrhythmia
  • Uncontrolled hypertension
  • Diabetes mellitus (Type 1 diabetes, poorly controlled type 2 diabetes)
  • Uncontrolled hypothyroidism or hyperthyroidism
  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: NCT01763827

  Hide Study Locations
Locations
United States, Alabama
Research Site
Birmingham, Alabama, United States, 35216
United States, Arizona
Research Site
Chandler, Arizona, United States, 85224
United States, Arkansas
Research Site
Little Rock, Arkansas, United States, 72205
United States, California
Research Site
Carmichael, California, United States, 95608
Research Site
Encinitas, California, United States, 92024
Research Site
San Diego, California, United States, 92111
Research Site
Tustin, California, United States, 92780
United States, Florida
Research Site
Jacksonville, Florida, United States, 32204
Research Site
Jacksonville, Florida, United States, 32216
Research Site
Miami, Florida, United States, 33144
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Ponte Vedra, Florida, United States, 32081
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Sanford, Florida, United States, 32771
United States, Idaho
Research Site
Boise, Idaho, United States, 83704
United States, Illinois
Research Site
Chicago, Illinois, United States, 60654
United States, Indiana
Research Site
Indianapolis, Indiana, United States, 46260
United States, Kansas
Research Site
Overland Park, Kansas, United States, 66202
United States, Kentucky
Research Site
Louisville, Kentucky, United States, 40213
United States, Maryland
Research Site
Bethesda, Maryland, United States, 20817
United States, Massachusetts
Research Site
Brockton, Massachusetts, United States, 02301
United States, Minnesota
Research Site
Edina, Minnesota, United States, 55435
United States, Mississippi
Research Site
Olive Branch, Mississippi, United States, 38654
United States, Nevada
Research Site
Las Vegas, Nevada, United States, 89148
United States, New York
Research Site
Endwell, New York, United States, 13760
Research Site
New Windsor, New York, United States, 12553
United States, North Carolina
Research Site
Raleigh, North Carolina, United States, 27609
Research Site
Raleigh, North Carolina, United States, 27612
United States, North Dakota
Research Site
Fargo, North Dakota, United States, 58103
United States, Ohio
Research Site
Akron, Ohio, United States, 44311
Research Site
Cincinnati, Ohio, United States, 45212
Research Site
Cincinnati, Ohio, United States, 45236
Research Site
Cincinnati, Ohio, United States, 45246
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Cleveland, Ohio, United States, 44122
United States, Oklahoma
Research Site
Norman, Oklahoma, United States, 73069
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Oklahoma City, Oklahoma, United States, 73103
United States, Pennsylvania
Research Site
Duncansville, Pennsylvania, United States, 16635
United States, South Carolina
Research Site
Anderson, South Carolina, United States, 29621
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Mt. Pleasant, South Carolina, United States, 29464
United States, South Dakota
Research Site
Rapid City, South Dakota, United States, 57702
United States, Tennessee
Research Site
Jackson, Tennessee, United States, 38305
United States, Texas
Research Site
Boerne, Texas, United States, 78006
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Dallas, Texas, United States, 75230
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San Antonio, Texas, United States, 78205
United States, Utah
Research Site
Salt Lake City, Utah, United States, 84124
United States, Virginia
Research Site
Norfolk, Virginia, United States, 23502
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Richmond, Virginia, United States, 23294
United States, Washington
Research Site
Renton, Washington, United States, 98057
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Seattle, Washington, United States, 98104
Australia, New South Wales
Research Site
Darlinghurst, New South Wales, Australia, 2010
Research Site
Maroubra, New South Wales, Australia, 2035
Australia, Queensland
Research Site
Carina Heights, Queensland, Australia, 4152
Research Site
Sherwood, Queensland, Australia, 4075
Belgium
Research Site
Anthée, Belgium, 5520
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Bruxelles, Belgium, 1080
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Gozee, Belgium, 6534
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Gribomont, Belgium, 6887
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Halen, Belgium, 3545
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Ham, Belgium, 3945
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Linkebeek, Belgium, 1630
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Retie, Belgium, 2470
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Tessenderlo, Belgium, 3980
Canada, Newfoundland and Labrador
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Bay Roberts, Newfoundland and Labrador, Canada, A0A 1G0
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Mount Pearl, Newfoundland and Labrador, Canada, A1N 1W7
Canada, Ontario
Research Site
Toronto, Ontario, Canada, M9W 4L6
Canada, Quebec
Research Site
Granby, Quebec, Canada, J2G 8Z9
Denmark
Research Site
Aalborg, Denmark, 9000
Research Site
Ballerup, Denmark, 2750
Research Site
Vejle, Denmark, 7100
France
Research Site
Gières, France, 38610
Research Site
Grenoble Cedex 9, France, 38043
Korea, Republic of
Research Site
Seoul, Korea, Republic of, 138-736
Research Site
Seoul, Korea, Republic of, 135-710
Research Site
Seoul, Korea, Republic of, 120-752
South Africa
Research Site
Alberton, Gauteng, South Africa, 1449
Research Site
Johannesburg, Gauteng, South Africa, 2196
Research Site
Parow, Western Cape, South Africa, 7505
Research Site
Somerset West, Western Cape, South Africa, 7130
Research Site
Worcester, Western Cape, South Africa, 6850
Research Site
Bloemfontein, South Africa, 9301
Taiwan
Research Site
Kaohsiung, Taiwan, 807
Research Site
Kaohsiung, Taiwan, 83301
Research Site
Taipei, Taiwan, 100
Turkey
Research Site
Istanbul, Turkey, 34093
Research Site
Istanbul, Turkey, 34662
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01763827     History of Changes
Other Study ID Numbers: 20110114
Study First Received: January 7, 2013
Last Updated: May 29, 2014
Health Authority: Brazil: National Health Surveillance Agency
South Korea: Korea Food and Drug Administration (KFDA)
Australia: Department of Health and Ageing Therapeutic Goods Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Belgium: Federal Agency for Medicinal Products and Health Products
Denmark: Danish Health and Medicines Authority
South Africa: Medicines Control Council
Turkey: Ministry of Health
Canada: Health Canada
United States: Food and Drug Administration
Taiwan: Taiwan Food and Drug Administration

Keywords provided by Amgen:
High cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia

Additional relevant MeSH terms:
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Ezetimibe
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 01, 2014