Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects (GAUSS)

• Absolute change from baseline in low density lipoprotein cholesterol at week 12 [ Time Frame: 12 week treatment duration ] [ Designated as safety issue: No ]
• Percent change from baseline in non-high density lipoprotein cholesterol at week 12 [ Time Frame: 12 week treatment duration ] [ Designated as safety issue: No ]
• Percent change from baseline in Apolipoprotein B at week 12 [ Time Frame: 12 week treatment duration ] [ Designated as safety issue: No ]
• Percent change from baseline in the total cholesterol/high density lipoprotein cholesterol ratio at week 12 [ Time Frame: 12 week treatment duration ] [ Designated as safety issue: No ]
• Percent change from baseline in Apolipoprotein B/Apolipoprotein A1 ratio at week 12 [ Time Frame: 12 week treatment duration ] [ Designated as safety issue: No ]

• Subject incidence of treatment emergent adverse events, serious adverse events, fatal adverse events, treatment related adverse events and adverse events leading to discontinuation of trial medication will be analyzed [ Time Frame: 12 week treatment duration ] [ Designated as safety issue: Yes ]
• Absolute change from baseline in LDL-C at week 12 [ Time Frame: 12 week treatment duration ] [ Designated as safety issue: No ]
• Percent change from baseline in non-HDL-C at week 12 [ Time Frame: 12 week treatment duration ] [ Designated as safety issue: No ]
• Percent change from baseline in ApoB at week 12 [ Time Frame: 12 week treatment duration ] [ Designated as safety issue: No ]
• Percent change from baseline in the total cholesterol/HDL-C ratio at wk 12 [ Time Frame: 12 week treatment duration ] [ Designated as safety issue: No ]
• Percent change from baseline in ApoB/ApoA1 ratio at week 12 [ Time Frame: 12 week treatment duration ] [ Designated as safety issue: No ]

The primary hypothesis is that a dose of AMG 145 every 4-weeks (Q4W) will be well tolerated and will result in greater lowering of Low Density Lipoprotein-Cholesterol at week 12 than ezetimibe in hypercholesterolemic subjects unable to tolerate an effective dose of a HMG-CoA reductase inhibitor.

• Biological: AMG 145
  Patients will receive AMG 145 every 4 weeks
• Other: Ezetimibe
  Patients will take Ezetimibe once a day
• Other: Placebo
  Patients will receive placebo every 4 weeks. All Patients at screening will participate in the placebo run-in

• Experimental: Group 4 with Ezetimibe
  Dose 3 of subcutaneous AMG 145. Oral Ezetimibe once a day
  Interventions:

  • Biological: AMG 145
  • Other: Ezetimibe
• Experimental: Group 1
  Dose 1 of subcutaneous AMG 145
  Intervention: Biological: AMG 145
• Experimental: Group 2
  Dose 2 of subcutaneous AMG 145
  Intervention: Biological: AMG 145
• Experimental: Group 3
  Dose 3 of subcutaneous AMG 145
  Intervention: Biological: AMG 145
• Experimental: Group 5
  Oral Ezetimibe & subcutaneous Placebo
  Interventions:

  • Other: Ezetimibe
  • Other: Placebo

Inclusion Criteria:

• Male or female ≥ 18 to ≤ 75 years of age
• On a statin or a low dose statin with stable dose for at least 4 weeks
• Lipid lowering therapy has been stable prior to enrollment
• Fasting triglycerides must be < 400 mg/dL.
• Subject not at LDL-C goal

Exclusion Criteria:

• NYHA III or IV heart failure or known left ventricular ejection fraction < 30%
• Uncontrolled cardiac arrhythmia
• Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months prior to randomization
• Type 1 diabetes or newly diagnosed type 2 diabetes (HbA1c > 8.5%)
• Uncontrolled hypertension