Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects 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: July 8, 2014
Last verified: July 2014
  Purpose

Primary hypothesis is that a dose regimen of evolocumab (AMG 145) when used as monotherapy will be well tolerated and will result in greater lowering of low density lipoprotein cholesterol (LDL-C) than placebo.


Condition Intervention Phase
Hyperlipidemia
Biological: evolocumab (AMG 145)
Other: Ezetimibe
Other: Placebo
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 AMG145 on Low Density Lipoprotein Cholesterol (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) after 12 weeks of treatment [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Absolute change from baseline in low density lipoprotein cholesterol (LDL-C) after 12 weeks of treatment [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Percent change from baseline in non-high density lipoprotein cholesterol (non-HDL-C) after 12 weeks of treatment [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Percent change from baseline in apolipoprotein B (ApoB) after 12 weeks of treatment [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Percent change from baseline in the total cholesterol/high density lipoprotein cholesterol (HDL-C) ratio after 12 weeks of treatment [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Percent change from baseline in apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) ratio after 12 weeks of treatment [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 411
Study Start Date: June 2011
Study Completion Date: April 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 5
Dose 5 of subcutaneous evolocumab (AMG 145)
Biological: evolocumab (AMG 145)
Patients will receive evolocumab (AMG 145) every 2 or 4 weeks
Placebo Comparator: Group 9
Subcutaneous placebo
Other: Placebo
Patients will receive Placebo every 2 weeks or 4 weeks. All patients at screening will participate in the placebo run-in.
Experimental: Group 6
Dose 6 of subcutaneous evolocumab (AMG 145)
Biological: evolocumab (AMG 145)
Patients will receive evolocumab (AMG 145) every 2 or 4 weeks
Experimental: Group 4
Dose 4 of subcutaneous evolocumab (AMG 145)
Biological: evolocumab (AMG 145)
Patients will receive evolocumab (AMG 145) every 2 or 4 weeks
Experimental: Group 3
Dose 3 of subcutaneous evolocumab (AMG 145)
Biological: evolocumab (AMG 145)
Patients will receive evolocumab (AMG 145) every 2 or 4 weeks
Experimental: Group 2
Dose 2 of subcutaneous evolocumab (AMG 145)
Biological: evolocumab (AMG 145)
Patients will receive evolocumab (AMG 145) every 2 or 4 weeks
Active Comparator: Group 7
Oral Ezetimibe
Other: Ezetimibe
Patients will take Ezetimibe daily
Placebo Comparator: Group 8
Subcutaneous placebo
Other: Placebo
Patients will receive Placebo every 2 weeks or 4 weeks. All patients at screening will participate in the placebo run-in.
Experimental: Group 1
Dose 1 of subcutaneous evolocumab (AMG 145)
Biological: evolocumab (AMG 145)
Patients will receive evolocumab (AMG 145) every 2 or 4 weeks

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
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
  • 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

  Show 58 Study Locations
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided by Amgen

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01375777     History of Changes
Other Study ID Numbers: 20101154
Study First Received: June 16, 2011
Last Updated: July 8, 2014
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
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 July 29, 2014