HyperlipidemiaPhase 2MENDELNCT01375777

Monoclonal Antibody Against PCSK9 to Reduce Elevated Low-density Lipoprotein Cholesterol (LDL-C) in Adults Currently Not Receiving Drug Therapy for Easing Lipid Levels

A Phase 2 study testing Evolocumab and Ezetimibe in people with Hyperlipidemia, run by Amgen at 58 sites in 5 countries.

Completed

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

Official record

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Trial summary

The primary objective was to evaluate the effect of 12 weeks of subcutaneous evolocumab (AMG 145) every 2 weeks (Q2W) or every 4 weeks (Q4W), compared with placebo, on the percent change from baseline in LDL-C when used as monotherapy in adults with hypercholesterolemia. Read more about this study

Who is it for?: Ages 18 to 75 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: 411 participants
Where: 58 sitesin 5 countries
Study dates: 6 Jul 2011to 2 Mar 2012
Phase: Phase 2
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 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female ≥ 18 to ≤ 75 years of age
Low density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL and < 190 mg/dL
Framingham risk score of 10% or less
Fasting triglycerides < 400 mg/dL

Who cannot join

History of coronary heart disease
New York Heart Association (NYHA) II - IV heart failure
Uncontrolled cardiac arrhythmia
Uncontrolled hypertension

Trial locations and contacts

58 sites in 5 countries.

Country

City, postcode or hospital

58 sites in 5 countries

United States41 sites

Research Site
Arlington, Texas, 76014
Research Site
Bethesda, Maryland, 20817
Research Site
Birmingham, Alabama, 35216
Research Site
Boerne, Texas, 78006
Research Site
Brockton, Massachusetts, 02301
Research Site
Brooklyn Center, Minnesota, 55430
Research Site
Chicago, Illinois, 60610
Research Site
Cincinnati, Ohio, 45219
Research Site
Cincinnati, Ohio, 45246
Research Site
Cleveland, Ohio, 44122
Research Site
Decatur, Georgia, 30035
Research Site
DeLand, Florida, 32720
Research Site
Duncansville, Pennsylvania, 16635
Research Site
Encinitas, California, 92024
Research Site
Endwell, New York, 13760
Research Site
Fargo, North Dakota, 58103
Research Site
Indianapolis, Indiana, 46260
Research Site
Inglewood, California, 90301
Research Site
Jacksonville, Florida, 32216
Research Site
Jacksonville, Florida, 32223
Research Site
Las Vegas, Nevada, 89148
Research Site
Little Rock, Arkansas, 72205
Research Site
Louisville, Kentucky, 40213
Research Site
Miami, Florida, 33143
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
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
San Antonio, Texas, 78205
Research Site
San Diego, California, 92111
Research Site
Sanford, Florida, 32771
Research Site
Seattle, Washington, 98122
Research Site
Tustin, California, 92780

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Belgium8 sites

Research Site
AnthÃ©e, 5520
Research Site
Dour, 7370
Research Site
Gozée, 6534
Research Site
Gribomont, 6887
Research Site
Halen, 3545
Research Site
Ham, 3945
Research Site
Linkebeek, 1630
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Retie, 2470

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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

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Denmark3 sites

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

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Australia2 sites

Research Site
Carina Heights, Queensland, 4152
Research Site
Maroubra, New South Wales, 2035

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About this study

Official title: A Randomized, Placebo- and Ezetimibe-controlled, Dose-ranging Study to Evaluate Tolerability and Efficacy of AMG 145 on LDL-C in Hypercholesterolemic Subjects With a 10-year Framingham Risk Score of 10% or Less

Conditions: Hyperlipidemia
Being tested: Evolocumab, Ezetimibe, Placebo to Evolocumab
Keywords: High cholesterol, Proprotein convertase subtilisin/kexin type 9 (PCSK9), Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia
Medical subject headings: Hyperlipidemias, Hypercholesterolemia, Hypercholesterolemia, Autosomal Dominant, 3

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 EvolocumabOther
Administered by subcutaneous injection

Study groups in NCT01375777
Study group	Role	What they receive
Placebo Q2W	Placebo comparator	Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks. Receives: Other: Placebo to Evolocumab
Placebo Q4W	Placebo comparator	Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks. Receives: Other: Placebo to Evolocumab
Ezetimibe	Active comparator	Participants received 10 mg ezetimibe orally once a day for 12 weeks. Receives: Drug: Ezetimibe
Evolocumab 70 mg Q2W	Experimental	Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. Receives: Biological: Evolocumab
Evolocumab 105 mg Q2W	Experimental	Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. Receives: Biological: Evolocumab
Evolocumab 140 mg Q2W	Experimental	Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. Receives: Biological: Evolocumab
Evolocumab 280 mg Q4W	Experimental	Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. Receives: Biological: Evolocumab
Evolocumab 350 mg Q4W	Experimental	Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. Receives: Biological: Evolocumab
Evolocumab 420 mg Q4W	Experimental	Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. Receives: Biological: Evolocumab

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
LDL-C was measured using ultracentrifugation.
Measured: Baseline and Week 12

Secondary outcomes (5)

Change From Baseline in LDL-C at Week 12
LDL-C was measured using ultracentrifugation.
Measured: Baseline and Week 12
Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in Apolipoprotein B at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio 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.

6 Jul 20112 Mar 2012

First posted17 Jun 2011 (estimated)
Study start6 Jul 2011
Primary completion2 Mar 2012
Study completion2 Mar 2012

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 (1)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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 411 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01375777
Sponsor's protocol ID: 20101154
Acronym: MENDEL
Status last verified: Nov 2022
First submitted: 16 Jun 2011
Last updated: 8 Nov 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Koren MJ, Scott R, Kim JB, Knusel B, Liu T, Lei L, Bolognese M, Wasserman SM. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 as monotherapy in patients with hypercholesterolaemia (MENDEL): a randomised, double-blind, placebo-controlled, phase 2 study. Lancet. 2012 Dec 8;380(9858):1995-2006. doi: 10.1016/S0140-6736(12)61771-1. Epub 2012 Nov 6.
PubMed 23141812

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?

See locations

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All Hyperlipidemia trials

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 Randomized, Placebo- and Ezetimibe-controlled, Dose-ranging Study to Evaluate Tolerability and Efficacy of AMG 145 on LDL-C in Hypercholesterolemic Subjects With a 10-year Framingham Risk Score of 10% or Less
ClinicalTrials.gov ID: NCT01375777
Acronym / sponsor ID: MENDEL / 20101154
Conditions: Hyperlipidemia
Keywords: High cholesterol, Proprotein convertase subtilisin/kexin type 9 (PCSK9), Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 411 participants (actual)
Lead sponsor: AmgenIndustry (pharma, biotech, devices)
Study start: 6 Jul 2011 (actual)
Primary completion: 2 Mar 2012 (actual)
Study completion: 2 Mar 2012 (actual)
First posted: 17 Jun 2011 (estimated)
Results: Posted 5 Oct 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: 9

Arm	Type	Receives
Placebo Q2W	Placebo comparator	Other: Placebo to EvolocumabParticipants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks.
Placebo Q4W	Placebo comparator	Other: Placebo to EvolocumabParticipants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks.
Ezetimibe	Active comparator	Drug: EzetimibeParticipants received 10 mg ezetimibe orally once a day for 12 weeks.
Evolocumab 70 mg Q2W	Experimental	Biological: EvolocumabParticipants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Evolocumab 105 mg Q2W	Experimental	Biological: EvolocumabParticipants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Evolocumab 140 mg Q2W	Experimental	Biological: EvolocumabParticipants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Evolocumab 280 mg Q4W	Experimental	Biological: EvolocumabParticipants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Evolocumab 350 mg Q4W	Experimental	Biological: EvolocumabParticipants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Evolocumab 420 mg Q4W	Experimental	Biological: EvolocumabParticipants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Male or female ≥ 18 to ≤ 75 years of age
Low density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL and < 190 mg/dL
Framingham risk score of 10% or less
Fasting triglycerides < 400 mg/dL

Key exclusion criteria (4 listed)

History of coronary heart disease
New York Heart Association (NYHA) II - IV heart failure
Uncontrolled cardiac arrhythmia
Uncontrolled hypertension

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 105 mg Q2W, Evolocumab 140 mg Q2W, Evolocumab 280 mg Q4W, Evolocumab 350 mg Q4W, Evolocumab 420 mg Q4W, Evolocumab 70 mg Q2W
EzetimibeAlso: ZetiaAdministered orally once a day	Drug	Ezetimibe
Placebo to EvolocumabAdministered by subcutaneous injection	Other	Placebo Q2W, Placebo Q4W

Primary outcome

Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
Time frame: Baseline and Week 12
LDL-C was measured using ultracentrifugation.

5 secondary outcomes

Change From Baseline in LDL-C at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in Apolipoprotein B at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12
Time frame: Baseline and Week 12

Results and safety

Results posted to the registry on 5 Oct 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	46	44
Placebo Q4W	45	42
Ezetimibe	46	45
Evolocumab 70 mg Q2W	45	45
Evolocumab 105 mg Q2W	46	45
Evolocumab 140 mg Q2W	45	44
Evolocumab 280 mg Q4W	46	44
Evolocumab 350 mg Q4W	46	44
Evolocumab 420 mg Q4W	46	44

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 = 45	Placebo Q4W n = 45	Ezetimibe n = 45	Evolocumab 70 mg Q2W n = 45	Evolocumab 105 mg Q2W n = 46	Evolocumab 140 mg Q2W n = 45	Evolocumab 280 mg Q4W n = 45	Evolocumab 350 mg Q4W n = 45	Evolocumab 420 mg Q4W n = 45
Value	-3.71 (2.66)	4.54 (2.64)	-14.26 (2.60)	-40.98 (2.64)	-43.87 (2.60)	-50.93 (2.66)	-39.02 (2.57)	-43.20 (2.57)	-47.98 (2.58)

Placebo Q2W vs Evolocumab 140 mg Q2W: LS Mean Treatment Difference: -47.23 (95% CI -54.52 to -39.93), p <0.001, ANCOVA
Placebo Q2W vs Evolocumab 105 mg Q2W: LS Mean Treatment Difference: -40.17 (95% CI -47.38 to -32.95), p <0.001, ANCOVA
Placebo Q2W vs Evolocumab 70 mg Q2W: LS Mean Treatment Difference: -32.27 (95% CI -44.53 to -30.02), p <0.001, ANCOVA

Population analysed: Full analysis set; missing ultracentrifugation (UC) LDL-C at Week 12 was imputed using last observation carried forward (LOCF) and calculated LDL-C.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: 12 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo Q2W	0 of 45 (0%)	10 of 45 (22.2%)	Not reported
Placebo Q4W	0 of 45 (0%)	10 of 45 (22.2%)	Not reported
Ezetimibe	0 of 45 (0%)	14 of 45 (31.1%)	Not reported
Evolocumab 70 mg Q2W	0 of 45 (0%)	11 of 45 (24.4%)	Not reported
Evolocumab 105 mg Q2W	1 of 46 (2.2%)	11 of 46 (23.9%)	Not reported
Evolocumab 140 mg Q2W	1 of 45 (2.2%)	14 of 45 (31.1%)	Not reported
Evolocumab 280 mg Q4W	0 of 45 (0%)	7 of 45 (15.6%)	Not reported
Evolocumab 350 mg Q4W	1 of 45 (2.2%)	11 of 45 (24.4%)	Not reported
Evolocumab 420 mg Q4W	0 of 45 (0%)	9 of 45 (20%)	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 23141812Koren MJ, Scott R, Kim JB, Knusel B, Liu T, Lei L, Bolognese M, Wasserman SM. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 as monotherapy in patients with hypercholesterolaemia (MENDEL): a randomised, double-blind, placebo-controlled, phase 2 study. Lancet. 2012 Dec 8;380(9858):1995-2006. doi: 10.1016/S0140-6736(12)61771-1. Epub 2012 Nov 6.
AmgenTrials clinical trials websiteLink provided by the sponsor.

Related trials for Hyperlipidemia

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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

58 sites in 5 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Evolocumab and Ezetimibe in people with Hyperlipidemia, run by Amgen at 58 sites in 5 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 4 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 58 sites in United States, Belgium, Canada, Denmark, Australia. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 5 Oct 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). 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 NCT01375777, which also lists 1 linked publication.

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.