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

  Show 83 Study Locations
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
Antibodies, Monoclonal
Ezetimibe
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 01, 2014