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: November 25, 2015
Last verified: November 2015
  Purpose
The primary objective was to evaluate the effect of 12 weeks of evolocumab subcutaneous (SC) monotherapy every 2 weeks (Q2W) and monthly (QM), compared with placebo and ezetimibe, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in adults with a 10-year Framingham risk score of 10% or less.

Condition Intervention Phase
Hyperlipidemia
Biological: Evolocumab
Drug: Ezetimibe
Biological: Placebo to Evolocumab
Other: Placebo to Ezetimibe
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 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:
  • Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
  • Change From Baseline in LDL-C at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL [ Time Frame: Weeks 10 and 12 ] [ Designated as safety issue: No ]
  • Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Non-HDL-C at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Apolipoprotein B at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-cholesterol Ratio at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-cholesterol Ratio at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Lipoprotein (a) at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Triglycerides at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Very Low Density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in VLDL-C at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in HDL-C at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]

Enrollment: 615
Study Start Date: January 2013
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Q2W
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.
Biological: Placebo to Evolocumab
Administered by subcutaneous injection
Other: Placebo to Ezetimibe
Administered orally once daily
Placebo Comparator: Placebo QM
Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
Biological: Placebo to Evolocumab
Administered by subcutaneous injection
Other: Placebo to Ezetimibe
Administered orally once daily
Active Comparator: Ezetimibe (Q2W)
Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
Drug: Ezetimibe
Administered orally once a day
Other Name: Zetia
Biological: Placebo to Evolocumab
Administered by subcutaneous injection
Active Comparator: Ezetimibe (QM)
Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
Drug: Ezetimibe
Administered orally once a day
Other Name: Zetia
Biological: Placebo to Evolocumab
Administered by subcutaneous injection
Experimental: Evolocumab Q2W
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
Biological: Evolocumab
Administered by subcutaneous injection
Other Names:
  • AMG 145
  • Repatha
Other: Placebo to Ezetimibe
Administered orally once daily
Experimental: Evolocumab QM
Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
Biological: Evolocumab
Administered by subcutaneous injection
Other Names:
  • AMG 145
  • Repatha
Other: Placebo to Ezetimibe
Administered orally once 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
  • National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) Framingham risk score of 10% or less
  • Fasting LDL-C ≥ 100 mg/dL (2.6 mmol/L) and <190 mg/dL
  • Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L)

Exclusion Criteria:

  • History of coronary heart disease
  • New York Heart Association (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
Research Site
Ponte Vedra, Florida, United States, 32081
Research Site
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
Research Site
Cleveland, Ohio, United States, 44122
United States, Oklahoma
Research Site
Norman, Oklahoma, United States, 73069
Research Site
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
Research Site
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
Research Site
Richmond, Virginia, United States, 23294
United States, Washington
Research Site
Renton, Washington, United States, 98057
Research Site
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
Research Site
Bruxelles, Belgium, 1080
Research Site
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
Research Site
Bay Roberts, Newfoundland and Labrador, Canada, A0A 1G0
Research Site
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, 120-752
Research Site
Seoul, Korea, Republic of, 135-710
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:
Publications:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01763827     History of Changes
Other Study ID Numbers: 20110114 
Study First Received: January 7, 2013
Results First Received: August 28, 2015
Last Updated: November 25, 2015
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
Antimetabolites
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on February 11, 2016