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

Tracking Information
First Submitted Date ICMJE	January 7, 2013
First Posted Date ICMJE	January 9, 2013
Results First Submitted Date	August 28, 2015
Results First Posted Date	December 30, 2015
Last Update Posted Date	December 30, 2015
Study Start Date ICMJE	January 2013
Actual Primary Completion Date	October 2013 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: November 25, 2015)	Percent Change From Baseline in Low-density Lipoprotein Cholesterol (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 NCT01763827 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: November 25, 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 Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL [ Time Frame: Weeks 10 and 12 ]; Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12 [ Time Frame: Week 12 ]; 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 ]; 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 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 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 Very Low Density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ]; Percent Change From Baseline in VLDL-C 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 HDL-C 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 (LDL-C) response (LDL-C < 70 mg/dL [1.8 mmol/L]) [ Time Frame: 10 and 12 Weeks ]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 ]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 ]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	Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy for Easing Lipid Levels-2
Official Title ICMJE	A Double-blind, Randomized, Placebo and Ezetimibe-controlled, Multicenter Study to Evaluate Safety and Efficacy of Lipid Lowering Monotherapy With AMG 145 in Subjects With a 10-Year Framingham Risk Score of 10% or Less
Brief Summary	The primary objective was to evaluate the effect of 12 weeks of evolocumab subcutaneous (SC) monotherapy every 2 weeks (Q2W) and monthly (QM), compared with placebo and ezetimibe, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in adults with a 10-year Framingham risk score of 10% or less.
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 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
Study Arms	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
Publications *	Koren MJ, Lundqvist P, Bolognese M, Neutel JM, Monsalvo ML, Yang J, Kim JB, Scott R, Wasserman SM, Bays H; MENDEL-2 Investigators. Anti-PCSK9 monotherapy for hypercholesterolemia: the MENDEL-2 randomized, controlled phase III clinical trial of evolocumab. J Am Coll Cardiol. 2014 Jun 17;63(23):2531-2540. doi: 10.1016/j.jacc.2014.03.018. Epub 2014 Mar 29.
* 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: November 25, 2015)	615
Original Estimated Enrollment ICMJE; (submitted: January 8, 2013)	600
Actual Study Completion Date	October 2013
Actual Primary Completion Date	October 2013 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
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, Korea, Republic of, South Africa, Taiwan, Turkey, United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01763827
Other Study ID Numbers ICMJE	20110114
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