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

  Show 58 Study Locations
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 August 22, 2016