HyperlipidemiaPhase 3MENDEL-2NCT01763827

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

A Phase 3 study testing Evolocumab and Ezetimibe in people with Hyperlipidemia, run by Amgen at 83 sites in 10 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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… Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Hyperlipidemia
What is being tested?: Evolocumab and Ezetimibe
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 615 participants
Where: 83 sitesin 10 countries
Study dates: 21 Jan 2013to 29 Oct 2013
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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)

Who cannot join

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

Trial locations and contacts

83 sites in 10 countries.

Country

City, postcode or hospital

83 sites in 10 countries

United States47 sites

Research Site
Akron, Ohio, 44311
Research Site
Anderson, South Carolina, 29621
Research Site
Bethesda, Maryland, 20817
Research Site
Birmingham, Alabama, 35216
Research Site
Boerne, Texas, 78006
Research Site
Boise, Idaho, 83704
Research Site
Brockton, Massachusetts, 02301
Research Site
Carmichael, California, 95608
Research Site
Chandler, Arizona, 85224
Research Site
Chicago, Illinois, 60654
Research Site
Cincinnati, Ohio, 45212
Research Site
Cincinnati, Ohio, 45236
Research Site
Cincinnati, Ohio, 45246
Research Site
Cleveland, Ohio, 44122
Research Site
Dallas, Texas, 75230
Research Site
Duncansville, Pennsylvania, 16635
Research Site
Edina, Minnesota, 55435
Research Site
Encinitas, California, 92024
Research Site
Endwell, New York, 13760
Research Site
Fargo, North Dakota, 58103
Research Site
Indianapolis, Indiana, 46260
Research Site
Jackson, Tennessee, 38305
Research Site
Jacksonville, Florida, 32204
Research Site
Jacksonville, Florida, 32216
Research Site
Las Vegas, Nevada, 89148
Research Site
Little Rock, Arkansas, 72205
Research Site
Louisville, Kentucky, 40213
Research Site
Miami, Florida, 33144
Research Site
Mt. Pleasant, South Carolina, 29464
Research Site
New Windsor, New York, 12553
Research Site
Norfolk, Virginia, 23502
Research Site
Norman, Oklahoma, 73069
Research Site
Oklahoma City, Oklahoma, 73103
Research Site
Olive Branch, Mississippi, 38654
Research Site
Overland Park, Kansas, 66202
Research Site
Ponte Vedra, Florida, 32081
Research Site
Raleigh, North Carolina, 27609
Research Site
Raleigh, North Carolina, 27612
Research Site
Rapid City, South Dakota, 57702
Research Site
Renton, Washington, 98057
Research Site
Richmond, Virginia, 23294
Research Site
Salt Lake City, Utah, 84124
Research Site
San Antonio, Texas, 78205
Research Site
San Diego, California, 92111
Research Site
Sanford, Florida, 32771
Research Site
Seattle, Washington, 98104
Research Site
Tustin, California, 92780

Other trials in United States

Belgium9 sites

Research Site
Anthée, 5520
Research Site
Brussels, 1080
Research Site
Gozée, 6534
Research Site
Gribomont, 6887
Research Site
Halen, 3545
Research Site
Ham, 3945
Research Site
Linkebeek, 1630
Research Site
Retie, 2470
Research Site
Tessenderlo, 3980

Other trials in Belgium

South Africa6 sites

Research Site
Alberton, Gauteng, 1449
Research Site
Bloemfontein, 9301
Research Site
Johannesburg, Gauteng, 2196
Research Site
Parow, Western Cape, 7505
Research Site
Somerset West, Western Cape, 7130
Research Site
Worcester, Western Cape, 6850

Other trials in South Africa

Australia4 sites

Research Site
Carina Heights, Queensland, 4152
Research Site
Darlinghurst, New South Wales, 2010
Research Site
Maroubra, New South Wales, 2035
Research Site
Sherwood, Queensland, 4075

Other trials in Australia

Canada4 sites

Research Site
Bay Roberts, Newfoundland and Labrador, A0A 1G0
Research Site
Granby, Quebec, J2G 8Z9
Research Site
Mount Pearl, Newfoundland and Labrador, A1N 1W7
Research Site
Toronto, Ontario, M9W 4L6

Other trials in Canada

Denmark3 sites

Research Site
Aalborg, 9000
Research Site
Ballerup Municipality, 2750
Research Site
Vejle, 7100

Other trials in Denmark

South Korea3 sites

Research Site
Seoul, 120-752
Research Site
Seoul, 135-710
Research Site
Seoul, 138-736

Other trials in South Korea

Taiwan3 sites

Research Site
Kaohsiung City, 807
Research Site
Kaohsiung City, 83301
Research Site
Taipei, 100

Other trials in Taiwan

France2 sites

Research Site
Gières, 38610
Research Site
Grenoble, 38043

Other trials in France

Turkey (Türkiye)2 sites

Research Site
Istanbul, 34093
Research Site
Istanbul, 34662

Other trials in Turkey (Türkiye)

About this study

Official 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

Conditions: Hyperlipidemia
Being tested: Evolocumab, Ezetimibe, Placebo to Evolocumab, Placebo to Ezetimibe
Keywords: High cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia
Medical subject headings: Hyperlipidemias, Hypercholesterolemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EvolocumabBiological
Also called AMG 145, Repatha
Administered by subcutaneous injection
EzetimibeDrug
Also called Zetia
Administered orally once a day
Placebo to EvolocumabBiological
Administered by subcutaneous injection
Placebo to EzetimibeOther
Administered orally once daily

Study groups in NCT01763827
Study group	Role	What they receive
Placebo Q2W	Placebo comparator	Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Receives: Biological: Placebo to Evolocumab; Other: Placebo to Ezetimibe
Placebo QM	Placebo comparator	Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Receives: Biological: Placebo to Evolocumab; Other: Placebo to Ezetimibe
Ezetimibe (Q2W)	Active comparator	Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Receives: Drug: Ezetimibe; Biological: Placebo to Evolocumab
Ezetimibe (QM)	Active comparator	Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Receives: Drug: Ezetimibe; Biological: Placebo to Evolocumab
Evolocumab Q2W	Experimental	Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Receives: Biological: Evolocumab; Other: Placebo to Ezetimibe
Evolocumab QM	Experimental	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks. Receives: Biological: Evolocumab; Other: Placebo to Ezetimibe

What is being measured

The primary outcome is the main question the study is designed to answer.

Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12

Secondary outcomes (20)

Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12
Change From Baseline in LDL-C at Week 12
Measured: Baseline and Week 12
Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL
Measured: Weeks 10 and 12
Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12
Measured: Week 12
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12
Percent Change From Baseline in Non-HDL-C at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12
Percent Change From Baseline in Apolipoprotein B at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-cholesterol Ratio at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12
Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-cholesterol Ratio at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12
Percent Change From Baseline in Lipoprotein (a) at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12
Percent Change From Baseline in Triglycerides at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in Very Low Density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12
Percent Change From Baseline in VLDL-C at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12
Percent Change From Baseline in HDL-C at Week 12
Measured: Baseline and Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

21 Jan 201329 Oct 2013

First posted9 Jan 2013 (estimated)
Study start21 Jan 2013
Primary completion10 Oct 2013
Study completion29 Oct 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (11)Papers the sponsor has linked to this study.
Other trials for HyperlipidemiaStudies of the same condition, open and under way.
More trials run by AmgenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 615 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01763827
Sponsor's protocol ID: 20110114
Acronym: MENDEL-2
Status last verified: Nov 2022
First submitted: 7 Jan 2013
Last updated: 8 Nov 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

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.
PubMed 24691094
Daviglus ML, Ferdinand KC, Lopez 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.
PubMed 33325247
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.
PubMed 32564340
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.
PubMed 29736889
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.
PubMed 29353350
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.
PubMed 30755061
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.
PubMed 30120772
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.
PubMed 28249876
Toth PP, Jones SR, Monsalvo ML, Elliott-Davey M, Lopez 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.
PubMed 32114889
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.
PubMed 29768954
May HT, Muhlestein JB, Ma Y, Lopez 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.
PubMed 30852766

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 8 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official 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
ClinicalTrials.gov ID: NCT01763827
Acronym / sponsor ID: MENDEL-2 / 20110114
Conditions: Hyperlipidemia
Keywords: High cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 615 participants (actual)
Lead sponsor: AmgenIndustry (pharma, biotech, devices)
Study start: 21 Jan 2013 (actual)
Primary completion: 10 Oct 2013 (actual)
Study completion: 29 Oct 2013 (actual)
First posted: 9 Jan 2013 (estimated)
Results: Posted 30 Dec 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 6

Arm	Type	Receives
Placebo Q2W	Placebo comparator	Biological: Placebo to Evolocumab, Other: Placebo to EzetimibeParticipants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.
Placebo QM	Placebo comparator	Biological: Placebo to Evolocumab, Other: Placebo to EzetimibeParticipants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
Ezetimibe (Q2W)	Active comparator	Drug: Ezetimibe, Biological: Placebo to EvolocumabParticipants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
Ezetimibe (QM)	Active comparator	Drug: Ezetimibe, Biological: Placebo to EvolocumabParticipants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
Evolocumab Q2W	Experimental	Biological: Evolocumab, Other: Placebo to EzetimibeParticipants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
Evolocumab QM	Experimental	Biological: Evolocumab, Other: Placebo to EzetimibeParticipants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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)

Key exclusion criteria (6 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EvolocumabAlso: AMG 145, RepathaAdministered by subcutaneous injection	Biological	Evolocumab Q2W, Evolocumab QM
EzetimibeAlso: ZetiaAdministered orally once a day	Drug	Ezetimibe (Q2W), Ezetimibe (QM)
Placebo to EvolocumabAdministered by subcutaneous injection	Biological	Ezetimibe (Q2W), Ezetimibe (QM), Placebo Q2W, Placebo QM
Placebo to EzetimibeAdministered orally once daily	Other	Evolocumab Q2W, Evolocumab QM, Placebo Q2W, Placebo QM

Primary outcome

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

20 secondary outcomes

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

Results and safety

Results posted to the registry on 30 Dec 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo Q2W	77	74
Placebo QM	78	77
Ezetimibe (Q2W)	77	73
Ezetimibe (QM)	77	76
Evolocumab Q2W	153	147
Evolocumab QM	153	151

Primary outcome: Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12

Time frame: Baseline and Week 12. Least squares mean (Standard Error). Unit: percent change

Measure	Placebo Q2W n = 76	Placebo QM n = 78	Ezetimibe (Q2W) n = 77	Ezetimibe (QM) n = 77	Evolocumab Q2W n = 153	Evolocumab QM n = 153
Value	0.10 (1.67)	-1.34 (1.54)	-17.75 (1.67)	-18.57 (1.56)	-57.04 (1.23)	-56.12 (1.12)

Placebo Q2W vs Evolocumab Q2W: LS Mean Treatment Difference: -57.14 (95% CI -61.14 to -53.14), p <0.001, Repeated measures linear effects model
Placebo QM vs Evolocumab QM: LS Mean Treatment Difference: -54.78 (95% CI -58.46 to -51.10), p <0.001, Repeated measures linear effects model
Ezetimibe (Q2W) vs Evolocumab Q2W: LS Mean Treatment Difference: -39.29 (95% CI -43.28 to -35.31), p <0.001, Repeated measures linear effects model

Population analysed: Full analysis set

Primary outcome: Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12

Time frame: Baseline and Weeks 10 and 12. Least squares mean (Standard Error). Unit: percent change

Measure	Placebo Q2W n = 76	Placebo QM n = 78	Ezetimibe (Q2W) n = 77	Ezetimibe (QM) n = 77	Evolocumab Q2W n = 153	Evolocumab QM n = 153
Value	-0.43 (1.45)	-1.41 (1.37)	-17.52 (1.46)	-19.12 (1.39)	-56.93 (1.07)	-58.81 (1.00)

Placebo Q2W vs Evolocumab Q2W: LS Mean Treatment Difference: -56.50 (95% CI -59.95 to -53.04), p <0.001, Repeated measures linear effects model
Placebo QM vs Evolocumab QM: LS Mean Treatment Difference: -57.40 (95% CI -60.66 to -54.14), p <0.001, Repeated measures linear effects model
Ezetimibe (Q2W) vs Evolocumab Q2W: LS Mean Treatment Difference: -39.41 (95% CI -42.87 to -35.94), p <0.001, Repeated measures linear effects model

Population analysed: Full analysis set

20 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the first dose of blinded investigational product until the end of the study (up to 14 weeks).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo Q2W	0 of 76 (0%)	9 of 76 (11.8%)	Not reported
Placebo QM	1 of 78 (1.3%)	4 of 78 (5.1%)	Not reported
Ezetimibe (Q2W)	0 of 77 (0%)	10 of 77 (13%)	Not reported
Ezetimibe (QM)	1 of 77 (1.3%)	4 of 77 (5.2%)	Not reported
Evolocumab Q2W	3 of 153 (2%)	12 of 153 (7.8%)	Not reported
Evolocumab QM	1 of 153 (0.7%)	12 of 153 (7.8%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 24691094Koren 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.
Background: PubMed 33325247Daviglus ML, Ferdinand KC, Lopez 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.
Background: PubMed 32564340Koren 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.
Background: PubMed 29736889Kuchimanchi 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.
Background: PubMed 29353350Kasichayanula 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.
Background: PubMed 30755061Shapiro 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.
Background: PubMed 30120772Stroes 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.
Background: PubMed 28249876Toth 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.
Background: PubMed 32114889Toth PP, Jones SR, Monsalvo ML, Elliott-Davey M, Lopez 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.
Background: PubMed 29768954Wasserman 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.
Background: PubMed 30852766May HT, Muhlestein JB, Ma Y, Lopez 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.
AmgenTrials clinical trials websiteLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

MD study director

Amgen

83 sites in 10 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Evolocumab and Ezetimibe in people with Hyperlipidemia, run by Amgen at 83 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 83 sites in United States, Belgium, South Africa, Australia, Canada and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Dec 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12 (time frame: Baseline and Week 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01763827, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2022.