Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy for Easing Lipid Levels-2 (MENDEL-2)

• 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 ]

• 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

• 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 ]

• 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 (LDL-C) response (LDL-C < 70 mg/dL [1.8 mmol/L]) [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
  Mean Low Density Lipoprotein-Cholesterol (LDL-C) response (LDL-C < 70 mg/dL [1.8 mmol/L])
• Low Density Lipoprotein-Cholesterol (LDL-C) response (LDL-C < 70 mg/dL [1.8 mmol/L]) [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
  Low Density Lipoprotein-Cholesterol (LDL-C) response (LDL-C < 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

• Biological: Evolocumab
  Administered by subcutaneous injection
  Other Names:

  • AMG 145
  • Repatha
• Drug: Ezetimibe
  Administered orally once a day
  Other Name: Zetia
• Biological: Placebo to Evolocumab
  Administered by subcutaneous injection
• Other: Placebo to Ezetimibe
  Administered orally once daily

• 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.
  Interventions:

  • Biological: Placebo to Evolocumab
  • Other: Placebo to Ezetimibe
• Placebo Comparator: Placebo QM
  Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
  Interventions:

  • Biological: Placebo to Evolocumab
  • Other: Placebo to Ezetimibe
• 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.
  Interventions:

  • Drug: Ezetimibe
  • Biological: Placebo to Evolocumab
• 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.
  Interventions:

  • Drug: Ezetimibe
  • Biological: Placebo to Evolocumab
• 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.
  Interventions:

  • Biological: Evolocumab
  • Other: Placebo to Ezetimibe
• 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.
  Interventions:

  • Biological: Evolocumab
  • Other: Placebo to Ezetimibe

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