Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects -2 (GAUSS-2)

• Percent Change From Baseline in LDL-C at Week 12 [ Time Frame: Baseline and Week 12 ]
• Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ]

• Mean percent change from baseline in low density lipoprotein-cholesterol [ Time Frame: 10 and 12 Weeks ]
  Mean percent change from baseline in low density lipoprotein-cholesterol
• Percent change from baseline in low density lipoprotein-cholesterol [ Time Frame: 12 Weeks ]
  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 ]
• Change From Baseline in LDL-C at Week 12 [ Time Frame: Baseline and Week 12 ]
• Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L) [ Time Frame: Weeks 10 and 12 ]
• Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12 [ Time Frame: Week 12 ]
• Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ]
• Percent Change From Baseline in Non-HDL-C at Week 12 [ Time Frame: Baseline and Week 12 ]
• Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ]
• Percent Change From Baseline in Apolipoprotein B at Week 12 [ Time Frame: Baseline and Week 12 ]
• Percent Change From Baseline in the Total Cholesterol/High Density Lipoprotein Cholesterol Ratio at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ]
• Percent Change From Baseline in the Total Cholesterol/High Density Lipoprotein Cholesterol Ratio at Week 12 [ Time Frame: Baseline and Week 12 ]
• 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 ]
• Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12 [ Time Frame: Baseline and Week 12 ]
• Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ]
• Percent Change From Baseline in Lipoprotein (a) at Week 12 [ Time Frame: Baseline and Week 12 ]
• Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ]
• Percent Change From Baseline in Triglycerides at Week 12 [ Time Frame: Baseline and Week 12 ]
• 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 ]
• Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12 [ Time Frame: Baseline and Week 12 ]
• Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ]
• Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at Week 12 [ Time Frame: Baseline and Week 12 ]

• Mean change from baseline in low density lipoprotein-cholesterol [ Time Frame: 10 and 12 Weeks ]
  Mean change from baseline in low density lipoprotein-cholesterol
• Change from baseline in low density lipoprotein-cholesterol [ Time Frame: 12 Weeks ]
  Change from baseline in low density lipoprotein-cholesterol
• Mean Low Density Lipoprotein-Cholesterol response (LDL-C < 70 mg/dL [1.8 mmol/L]) [ Time Frame: 10 and 12 Weeks ]
  Mean Low Density Lipoprotein-Cholesterol response (LDL-C < 70 mg/dL [1.8 mmol/L])
• Low Density Lipoprotein-Cholesterol response (LDL-C < 70 mg/dL [1.8 mmol/L]) [ Time Frame: 12 Weeks ]
  Low Density Lipoprotein-Cholesterol 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 ]
  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 ]
  Percent change from baseline in non-high density lipoprotein-cholesterol
• Mean percent change from baseline in apolipoprotein B [ Time Frame: 10 and 12 Weeks ]
  Mean percent change from baseline in apolipoprotein B
• Percent change from baseline in apolipoprotein B [ Time Frame: 12 Weeks ]
  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 ]
  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 ]
  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 ]
  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 ]
  Percent change from baseline in apolipoprotein B/apolipoprotein A1 ratio
• Mean percent change from baseline in lipoprotein (a) [ Time Frame: 10 and 12 Weeks ]
  Mean percent change from baseline in lipoprotein (a)
• Percent change from baseline in lipoprotein (a) [ Time Frame: 12 Weeks ]
  Percent change from baseline in lipoprotein (a)
• Mean percent change from baseline in triglycerides [ Time Frame: 10 and 12 Weeks ]
  Mean percent change from baseline in triglycerides
• Percent change from baseline in triglycerides [ Time Frame: 12 Weeks ]
  Percent change from baseline in triglycerides
• Mean percent change from baseline in high density lipoprotein-cholesterol [ Time Frame: 10 and 12 Weeks ]
  Mean percent change from baseline in high density lipoprotein-cholesterol
• Percent change from baseline in high density lipoprotein-cholesterol [ Time Frame: 12 Weeks ]
  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 ]
  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 ]
  Percent change from baseline in very low density lipoprotein-cholesterol

• Biological: Evolocumab
  Subcutaneous injection
  Other Names:

  • AMG 145
  • Repatha
• Drug: Placebo to Evolocumab
  Subcutaneous injection
• Drug: Ezetimibe
  Tablet for oral administration
  Other Name: Zetia
• Drug: Placebo to Ezetimibe
  Tablet for oral administration

• 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: Placebo to Evolocumab
  • Drug: Ezetimibe
• 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: Placebo to Evolocumab
  • Drug: Ezetimibe
• 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
  • Drug: 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
  • Drug: Placebo to Ezetimibe

• Cho L, Rocco M, Colquhoun D, Sullivan D, Rosenson RS, Dent R, Xue A, Scott R, Wasserman SM, Stroes E. Design and rationale of the GAUSS-2 study trial: a double-blind, ezetimibe-controlled phase 3 study of the efficacy and tolerability of evolocumab (AMG 145) in subjects with hypercholesterolemia who are intolerant of statin therapy. Clin Cardiol. 2014 Mar;37(3):131-9. doi: 10.1002/clc.22248. Epub 2014 Jan 29.
• Stroes E, Colquhoun D, Sullivan D, Civeira F, Rosenson RS, Watts GF, Bruckert E, Cho L, Dent R, Knusel B, Xue A, Scott R, Wasserman SM, Rocco M; GAUSS-2 Investigators. Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab. J Am Coll Cardiol. 2014 Jun 17;63(23):2541-8. doi: 10.1016/j.jacc.2014.03.019. Epub 2014 Mar 30.

Inclusion Criteria:

• Male or female ≥ 18 to ≤ 80 years of age
• Not on a statin or on a low dose statin with stable dose for at least 4 weeks
• History of intolerance to at least 2 statins
• Subject not at LDL-C goal
• Lipid lowering therapy has been stable prior to enrolment for at least 4 weeks.
• Fasting triglycerides ≤ 400 mg/dL

Exclusion Criteria:

• New York Heart Association (NYHA) III or IV heart failure
• Uncontrolled cardiac arrhythmia
• Uncontrolled hypertension
• Type 1 diabetes, poorly controlled type 2 diabetes
• Uncontrolled hypothyroidism or hyperthyroidism