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

Tracking Information
First Submitted Date ICMJE	January 7, 2013
First Posted Date ICMJE	January 9, 2013
Results First Submitted Date	September 2, 2015
Results First Posted Date	December 22, 2015
Last Update Posted Date	December 22, 2015
Study Start Date ICMJE	January 2013
Actual Primary Completion Date	November 2013 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: November 18, 2015)	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 ]
Original Primary Outcome Measures ICMJE; (submitted: January 8, 2013)	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 History	Complete list of historical versions of study NCT01763905 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: November 18, 2015)	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 ]
Original Secondary Outcome Measures ICMJE; (submitted: January 8, 2013)	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
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects -2
Official Title ICMJE	A Double-blind, Randomized, Multicenter Study to Evaluate Safety and Efficacy of AMG 145, Compared With Ezetimibe, in Hypercholesterolemic Subjects Unable to Tolerate an Effective Dose of a HMG-CoA Reductase Inhibitor
Brief Summary	The primary objective was to evaluate the effect of 12 weeks of subcutaneous (SC) evolocumab every 2 weeks (Q2W) and monthly (QM), compared with ezetimibe, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic adults unable to tolerate an effective dose of a statin (HMG-CoA (5-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors).
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Hyperlipidemia
Intervention ICMJE	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
Study Arms	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
Publications *	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):2541-2548. doi: 10.1016/j.jacc.2014.03.019. Epub 2014 Mar 30.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: December 10, 2013)	307
Original Estimated Enrollment ICMJE; (submitted: January 8, 2013)	300
Actual Study Completion Date	November 2013
Actual Primary Completion Date	November 2013 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 80 Years (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Australia, Belgium, Canada, Denmark, France, Germany, Hong Kong, Netherlands, Poland, South Africa, Spain, Switzerland, United Kingdom, United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01763905
Other Study ID Numbers ICMJE	20110116; 2012-001364-30 ( EudraCT Number )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Amgen
Study Sponsor ICMJE	Amgen
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: MD Amgen
PRS Account	Amgen
Verification Date	November 2015
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP