Hyperlipidemia Clinical Trial
— MENDEL-2Official title:
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
| Verified date | November 2022 |
| Source | Amgen |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 615 |
| Est. completion date | October 29, 2013 |
| Est. primary completion date | October 10, 2013 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 80 Years |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Research Site | Carina Heights | Queensland |
| Australia | Research Site | Darlinghurst | New South Wales |
| Australia | Research Site | Maroubra | New South Wales |
| Australia | Research Site | Sherwood | Queensland |
| Belgium | Research Site | Anthée | |
| Belgium | Research Site | Bruxelles | |
| Belgium | Research Site | Gozee | |
| Belgium | Research Site | Gribomont | |
| Belgium | Research Site | Halen | |
| Belgium | Research Site | Ham | |
| Belgium | Research Site | Linkebeek | |
| Belgium | Research Site | Retie | |
| Belgium | Research Site | Tessenderlo | |
| Canada | Research Site | Bay Roberts | Newfoundland and Labrador |
| Canada | Research Site | Granby | Quebec |
| Canada | Research Site | Mount Pearl | Newfoundland and Labrador |
| Canada | Research Site | Toronto | Ontario |
| Denmark | Research Site | Aalborg | |
| Denmark | Research Site | Ballerup | |
| Denmark | Research Site | Vejle | |
| France | Research Site | Gières | |
| France | Research Site | Grenoble Cedex 9 | |
| Korea, Republic of | Research Site | Seoul | |
| Korea, Republic of | Research Site | Seoul | |
| Korea, Republic of | Research Site | Seoul | |
| South Africa | Research Site | Alberton | Gauteng |
| South Africa | Research Site | Bloemfontein | |
| South Africa | Research Site | Johannesburg | Gauteng |
| South Africa | Research Site | Parow | Western Cape |
| South Africa | Research Site | Somerset West | Western Cape |
| South Africa | Research Site | Worcester | Western Cape |
| Taiwan | Research Site | Kaohsiung | |
| Taiwan | Research Site | Kaohsiung | |
| Taiwan | Research Site | Taipei | |
| Turkey | Research Site | Istanbul | |
| Turkey | Research Site | Istanbul | |
| United States | Research Site | Akron | Ohio |
| United States | Research Site | Anderson | South Carolina |
| United States | Research Site | Bethesda | Maryland |
| United States | Research Site | Birmingham | Alabama |
| United States | Research Site | Boerne | Texas |
| United States | Research Site | Boise | Idaho |
| United States | Research Site | Brockton | Massachusetts |
| United States | Research Site | Carmichael | California |
| United States | Research Site | Chandler | Arizona |
| United States | Research Site | Chicago | Illinois |
| United States | Research Site | Cincinnati | Ohio |
| United States | Research Site | Cincinnati | Ohio |
| United States | Research Site | Cincinnati | Ohio |
| United States | Research Site | Cleveland | Ohio |
| United States | Research Site | Dallas | Texas |
| United States | Research Site | Duncansville | Pennsylvania |
| United States | Research Site | Edina | Minnesota |
| United States | Research Site | Encinitas | California |
| United States | Research Site | Endwell | New York |
| United States | Research Site | Fargo | North Dakota |
| United States | Research Site | Indianapolis | Indiana |
| United States | Research Site | Jackson | Tennessee |
| United States | Research Site | Jacksonville | Florida |
| United States | Research Site | Jacksonville | Florida |
| United States | Research Site | Las Vegas | Nevada |
| United States | Research Site | Little Rock | Arkansas |
| United States | Research Site | Louisville | Kentucky |
| United States | Research Site | Miami | Florida |
| United States | Research Site | Mount Pleasant | South Carolina |
| United States | Research Site | New Windsor | New York |
| United States | Research Site | Norfolk | Virginia |
| United States | Research Site | Norman | Oklahoma |
| United States | Research Site | Oklahoma City | Oklahoma |
| United States | Research Site | Olive Branch | Mississippi |
| United States | Research Site | Overland Park | Kansas |
| United States | Research Site | Ponte Vedra | Florida |
| United States | Research Site | Raleigh | North Carolina |
| United States | Research Site | Raleigh | North Carolina |
| United States | Research Site | Rapid City | South Dakota |
| United States | Research Site | Renton | Washington |
| United States | Research Site | Richmond | Virginia |
| United States | Research Site | Salt Lake City | Utah |
| United States | Research Site | San Antonio | Texas |
| United States | Research Site | San Diego | California |
| United States | Research Site | Sanford | Florida |
| United States | Research Site | Seattle | Washington |
| United States | Research Site | Tustin | California |
| Lead Sponsor | Collaborator |
|---|---|
| Amgen |
United States, Australia, Belgium, Canada, Denmark, France, Korea, Republic of, South Africa, Taiwan, Turkey,
Daviglus ML, Ferdinand KC, López JAG, Wu Y, Monsalvo ML, Rodriguez CJ. Effects of Evolocumab on Low-Density Lipoprotein Cholesterol, Non-High Density Lipoprotein Cholesterol, Apolipoprotein B, and Lipoprotein(a) by Race and Ethnicity: A Meta-Analysis of Individual Participant Data From Double-Blind and Open-Label Extension Studies. J Am Heart Assoc. 2021 Jan 5;10(1):e016839. doi: 10.1161/JAHA.120.016839. Epub 2020 Dec 16. — View Citation
Kasichayanula S, Grover A, Emery MG, Gibbs MA, Somaratne R, Wasserman SM, Gibbs JP. Clinical Pharmacokinetics and Pharmacodynamics of Evolocumab, a PCSK9 Inhibitor. Clin Pharmacokinet. 2018 Jul;57(7):769-779. doi: 10.1007/s40262-017-0620-7. Review. — View Citation
Koren MJ, Jones PH, Robinson JG, Sullivan D, Cho L, Hucko T, Lopez JAG, Fleishman AN, Somaratne R, Stroes E. A Comparison of Ezetimibe and Evolocumab for Atherogenic Lipid Reduction in Four Patient Populations: A Pooled Efficacy and Safety Analysis of Three Phase 3 Studies. Cardiol Ther. 2020 Dec;9(2):447-465. doi: 10.1007/s40119-020-00181-8. Epub 2020 Jun 20. — View Citation
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. — View Citation
Kuchimanchi M, Grover A, Emery MG, Somaratne R, Wasserman SM, Gibbs JP, Doshi S. Population pharmacokinetics and exposure-response modeling and simulation for evolocumab in healthy volunteers and patients with hypercholesterolemia. J Pharmacokinet Pharmacodyn. 2018 Jun;45(3):505-522. doi: 10.1007/s10928-018-9592-y. Epub 2018 May 7. — View Citation
May HT, Muhlestein JB, Ma Y, López JAG, Coll B, Nelson J. Effects of Evolocumab on the ApoA1 Remnant Ratio: A Pooled Analysis of Phase 3 Studies. Cardiol Ther. 2019 Jun;8(1):91-102. doi: 10.1007/s40119-019-0133-6. Epub 2019 Mar 9. — View Citation
Shapiro MD, Minnier J, Tavori H, Kassahun H, Flower A, Somaratne R, Fazio S. Relationship Between Low-Density Lipoprotein Cholesterol and Lipoprotein(a) Lowering in Response to PCSK9 Inhibition With Evolocumab. J Am Heart Assoc. 2019 Feb 19;8(4):e010932. doi: 10.1161/JAHA.118.010932. — View Citation
Stroes E, Robinson JG, Raal FJ, Dufour R, Sullivan D, Kassahun H, Ma Y, Wasserman SM, Koren MJ. Consistent LDL-C response with evolocumab among patient subgroups in PROFICIO: A pooled analysis of 3146 patients from phase 3 studies. Clin Cardiol. 2018 Oct;41(10):1328-1335. doi: 10.1002/clc.23049. Epub 2018 Oct 21. — View Citation
Toth PP, Descamps O, Genest J, Sattar N, Preiss D, Dent R, Djedjos C, Wu Y, Geller M, Uhart M, Somaratne R, Wasserman SM; PROFICIO Investigators. Pooled Safety Analysis of Evolocumab in Over 6000 Patients From Double-Blind and Open-Label Extension Studies. Circulation. 2017 May 9;135(19):1819-1831. doi: 10.1161/CIRCULATIONAHA.116.025233. Epub 2017 Mar 1. — View Citation
Toth PP, Jones SR, Monsalvo ML, Elliott-Davey M, López JAG, Banach M. Effect of Evolocumab on Non-High-Density Lipoprotein Cholesterol, Apolipoprotein B, and Lipoprotein(a): A Pooled Analysis of Phase 2 and Phase 3 Studies. J Am Heart Assoc. 2020 Mar 3;9(5):e014129. doi: 10.1161/JAHA.119.014129. Epub 2020 Mar 2. — View Citation
Wasserman SM, Sabatine MS, Koren MJ, Giugliano RP, Legg JC, Emery MG, Doshi S, Liu T, Somaratne R, Gibbs JP. Comparison of LDL-C Reduction Using Different Evolocumab Doses and Intervals: Biological Insights and Treatment Implications. J Cardiovasc Pharmacol Ther. 2018 Sep;23(5):423-432. doi: 10.1177/1074248418774043. Epub 2018 May 16. — View Citation
* Note: There are 11 references in all — Click here to view all references
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12 | Baseline and Week 12 | ||
| Primary | Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 | ||
| Secondary | Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 | ||
| Secondary | Change From Baseline in LDL-C at Week 12 | Baseline and Week 12 | ||
| Secondary | Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL | Weeks 10 and 12 | ||
| Secondary | Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12 | Week 12 | ||
| Secondary | Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 | ||
| Secondary | Percent Change From Baseline in Non-HDL-C at Week 12 | Baseline and Week 12 | ||
| Secondary | Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 | ||
| Secondary | Percent Change From Baseline in Apolipoprotein B at Week 12 | Baseline and Week 12 | ||
| Secondary | Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-cholesterol Ratio at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 | ||
| Secondary | Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-cholesterol Ratio at Week 12 | Baseline and Week 12 | ||
| Secondary | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 | ||
| Secondary | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12 | Baseline and Week 12 | ||
| Secondary | Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 | ||
| Secondary | Percent Change From Baseline in Lipoprotein (a) at Week 12 | Baseline and Week 12 | ||
| Secondary | Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 | ||
| Secondary | Percent Change From Baseline in Triglycerides at Week 12 | Baseline and Week 12 | ||
| Secondary | Percent Change From Baseline in Very Low Density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 | ||
| Secondary | Percent Change From Baseline in VLDL-C at Week 12 | Baseline and Week 12 | ||
| Secondary | Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 | ||
| Secondary | Percent Change From Baseline in HDL-C at Week 12 | Baseline and Week 12 |
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