Monoclonal Antibody Against PCSK9 to Reduce Elevated Low-density Lipoprotein Cholesterol (LDL-C) in Adults Currently Not Receiving Drug Therapy for Easing Lipid Levels (MENDEL)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01375777
First received: June 16, 2011
Last updated: September 3, 2015
Last verified: September 2015
  Purpose
The primary objective was to evaluate the effect of 12 weeks of subcutaneous evolocumab (AMG 145) every 2 weeks (Q2W) or every 4 weeks (Q4W), compared with placebo, on the percent change from baseline in LDL-C when used as monotherapy in adults with hypercholesterolemia.

Condition Intervention Phase
Hyperlipidemia
Biological: Evolocumab
Drug: Ezetimibe
Other: Placebo to Evolocumab
Phase 2

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 Randomized, Placebo- and Ezetimibe-controlled, Dose-ranging Study to Evaluate Tolerability and Efficacy of AMG 145 on LDL-C in Hypercholesterolemic 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 ]
    LDL-C was measured using ultracentrifugation.


Secondary Outcome Measures:
  • Change From Baseline in LDL-C at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    LDL-C was measured using ultracentrifugation.

  • Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (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 Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]

Enrollment: 411
Study Start Date: July 2011
Study Completion Date: March 2012
Primary Completion Date: March 2012 (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) for 12 weeks.
Other: Placebo to Evolocumab
Administered by subcutaneous injection
Placebo Comparator: Placebo Q4W
Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks.
Other: Placebo to Evolocumab
Administered by subcutaneous injection
Active Comparator: Ezetimibe
Participants received 10 mg ezetimibe orally once a day for 12 weeks.
Drug: Ezetimibe
Administered orally once a day
Other Name: Zetia
Experimental: Evolocumab 70 mg Q2W
Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Biological: Evolocumab
Administered by subcutaneous injection
Other Names:
  • AMG 145
  • Repatha
Experimental: Evolocumab 105 mg Q2W
Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Biological: Evolocumab
Administered by subcutaneous injection
Other Names:
  • AMG 145
  • Repatha
Experimental: Evolocumab 140 mg Q2W
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Biological: Evolocumab
Administered by subcutaneous injection
Other Names:
  • AMG 145
  • Repatha
Experimental: Evolocumab 280 mg Q4W
Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Biological: Evolocumab
Administered by subcutaneous injection
Other Names:
  • AMG 145
  • Repatha
Experimental: Evolocumab 350 mg Q4W
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Biological: Evolocumab
Administered by subcutaneous injection
Other Names:
  • AMG 145
  • Repatha
Experimental: Evolocumab 420 mg Q4W
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Biological: Evolocumab
Administered by subcutaneous injection
Other Names:
  • AMG 145
  • Repatha

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female ≥ 18 to ≤ 75 years of age
  • Low density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL and < 190 mg/dL
  • Framingham risk score of 10% or less
  • Fasting triglycerides < 400 mg/dL

Exclusion Criteria:

  • History of coronary heart disease
  • New York Heart Association (NYHA) II - IV heart failure
  • Uncontrolled cardiac arrhythmia
  • 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: NCT01375777

  Hide Study Locations
Locations
United States, Alabama
Research Site
Birmingham, Alabama, United States, 35216
United States, Arkansas
Research Site
Little Rock, Arkansas, United States, 72205
United States, California
Research Site
Encinitas, California, United States, 92024
Research Site
Inglewood, California, United States, 90301
Research Site
San Diego, California, United States, 92111
Research Site
Tustin, California, United States, 92780
United States, Florida
Research Site
DeLand, Florida, United States, 32720
Research Site
Jacksonville, Florida, United States, 32216
Research Site
Jacksonville, Florida, United States, 32223
Research Site
Miami, Florida, United States, 33143
Research Site
Miami, Florida, United States, 33144
Research Site
Ponte Vedra, Florida, United States, 32081
Research Site
Sanford, Florida, United States, 32771
United States, Georgia
Research Site
Decatur, Georgia, United States, 30035
United States, Illinois
Research Site
Chicago, Illinois, United States, 60610
United States, Indiana
Research Site
Indianapolis, Indiana, United States, 46260
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
Brooklyn Center, Minnesota, United States, 55430
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
Cincinnati, Ohio, United States, 45246
Research Site
Cincinnati, Ohio, United States, 45219
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
Mt. Pleasant, South Carolina, United States, 29464
United States, South Dakota
Research Site
Rapid City, South Dakota, United States, 57702
United States, Texas
Research Site
Arlington, Texas, United States, 76014
Research Site
Boerne, Texas, United States, 78006
Research Site
San Antoio, Texas, United States, 78205
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, 98122
Australia, New South Wales
Research Site
Maroubra, New South Wales, Australia, 2035
Australia, Queensland
Research Site
Carina Heights, Queensland, Australia, 4152
Belgium
Research Site
Anthée, Belgium, 5520
Research Site
Dour, Belgium, 7370
Research Site
Gozee, Belgium, 6534
Research Site
Gribomont, Belgium, 6887
Research Site
Halen, Belgium, 3545
Research Site
Ham, Belgium, 3945
Research Site
Linkebeek, Belgium, 1630
Research Site
Retie, Belgium, 2470
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
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
Publications:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01375777     History of Changes
Other Study ID Numbers: 20101154 
Study First Received: June 16, 2011
Results First Received: September 3, 2015
Last Updated: September 3, 2015
Health Authority: Canada: Health Canada
Denmark: Laegemiddelstyrelsen
Germany: Paul_Ehrlich-Institut Bundesamt fur Sera und Impfstoffe
South Africa: Medicines Control Council
United States: Food and Drug Administration
Australia: Therapeutic Goods Administration
Belgium: Directorate-General for Medicinal Products

Keywords provided by Amgen:
High cholesterol
Proprotein convertase subtilisin/kexin type 9 (PCSK9)
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
Lipid Regulating Agents

ClinicalTrials.gov processed this record on July 25, 2016