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HypercholesterolemiaPhase 3NCT06450366

A Study to Evaluate the Efficacy and Safety of Enlicitide (MK-0616, Oral PCSK9 Inhibitor) Compared With Ezetimibe or Bempedoic Acid or Ezetimibe and Bempedoic Acid in Adults With Hypercholesterolemia (MK-0616-018/CORALreef AddOn)

A Phase 3 study testing Enlicitide, Ezetimibe and Bempedoic Acid in people with Hypercholesterolemia, run by Merck Sharp & Dohme LLC at 35 sites in 8 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 main purpose of this study is to assess whether enlicitide is superior to ezetimibe or bempedoic acid or ezetimibe + bempedoic acid in reducing low-density lipoprotein cholesterol (LDL-C) in participants with hypercholesterolemia, and to evaluate its safety and tolerability. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hypercholesterolemia
What is being tested?
Enlicitide, Ezetimibe and Bempedoic Acid
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
301 participants
Where
35 sitesin 8 countries
Study dates
8 Jul 2024to 28 Mar 2025
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Has either a) history of a major atherosclerotic cardiovascular disease (ASCVD) event or b) if no history of a major ASCVD event, has intermediate to high risk for development of a first major ASCVD event
  • Has fasted lipid values (evaluated by the central laboratory) at Visit 1 (Screening) as follows: a) history of a major ASCVD event with LDL-C ≥55 mg/dL (≥1.42 mmol/L) OR b) No history of a major ASCVD event with low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL (≥1.81 mmol/L)
  • Is treated with a low, moderate, or high intensity statin (±non-statin lipid lowering therapy [LLT])
  • Is on a stable dose of all background LLTs with no planned medication or dose changes during the study
  • Is an individual of any sex/gender, from 18 years of age inclusive, at the time of providing the informed consent

Who cannot join

  • Has a history of homozygous familial hypercholesterolemia (FH) based on genetic or clinical criteria, compound heterozygous familial hypercholesterolemia (HeFH), or double HeFH
  • Has New York Heart Association class IV heart failure, or last known left ventricular ejection fraction ≤25% by any imaging method, or had a heart failure hospitalization within 3 months before Visit 1 (Screening)
  • Participants with a history of tendon disorder or tendon rupture
  • Participants with a history of gout
  • Is undergoing or previously underwent an LDL-C apheresis program within 3 months before Visit 1 (Screening) or plans to initiate an LDL-C apheresis program
  • Was previously treated/is being treated with certain other cholesterol lowering medications, including ezetimibe, bempedoic acid, or protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors without adequate washout

Trial locations and contacts

35 sites in 8 countries.

35 sites in 8 countries

United States7 sites

  • Healthcare Research Network - Chicago ( Site 1507)

    Flossmoor, Illinois, 60422

  • Piedmont Research Partners ( Site 1506)

    Fort Mill, South Carolina, 29707

  • Velocity Clinical Research, Gulfport ( Site 1505)

    Gulfport, Mississippi, 39503

  • Clinical Trials Research ( Site 1509)

    Lincoln, California, 95648

  • L-MARC Research Center ( Site 1501)

    Louisville, Kentucky, 40213

  • Rainier Clinical Research Center ( Site 1502)

    Renton, Washington, 98057

  • Velocity Clinical Research Rockville ( Site 1503)

    Rockville, Maryland, 20854

Other trials in United States

Canada5 sites

  • Cambridge Cardiac Care Centre ( Site 1603)

    Cambridge, Ontario, N1R 6V6

  • Institut de Cardiologie de Montreal ( Site 1604)

    Montreal, Quebec, H1T 1C8

  • North York Diagnostic and Cardiac Centre ( Site 1605)

    North York, Ontario, M6B 3H7

  • Diex Recherche Trois-Rivieres ( Site 1602)

    Trois-Rivières, Quebec, G9A 4P3

  • The Medical Arts Health Research Group ( Site 1606)

    Vancouver, British Columbia, V7M 2H4

Other trials in Canada

Spain5 sites

  • Hospital San Rafael de Coruna ( Site 0805)

    A Coruña, La Coruna, 15006

  • EAP Sardenya ( Site 0800)

    Barcelona, 08025

  • Hospital Universitari Vall d'Hebron ( Site 0803)

    Barcelona, 08035

  • Hospital de Figueres ( Site 0804)

    Figueres, Gerona, 17600

  • Hospital Universitario Virgen de la Victoria-UGC Endocrinologia y nutricion ( Site 0801)

    Málaga, Andalusia, 29010

Other trials in Spain

France4 sites

  • Hospices Civils de Lyon - Hopital Louis Pradel ( Site 0501)

    Bron, Rhone, 69677

  • Hôpital Arnaud de Villeneuve - CHU Montpellier ( Site 0505)

    Montpellier, Herault, 34090

  • Hôpital Nord Guillaume-et-René-Laennec / CHU de Nantes-CIC Endocrinology-Diabetology-Nutrition ( Sit

    Nantes, Loire-Atlantique, 44093

  • Hôpital Bichat - Claude-Bernard ( Site 0504)

    Paris, 75018

Other trials in France

Israel4 sites

  • Yitzhak Shamir Medical Center. ( Site 0702)

    Beer Yaakov, 70300

  • Assuta Beersheba MC ( Site 0704)

    Beersheba, 8489507

  • Rambam Health Care Campus ( Site 0700)

    Haifa, 3109601

  • Meir Medical Center. ( Site 0703)

    Kfar Saba, 4428164

Other trials in Israel

Taiwan4 sites

  • National Cheng Kung University Hospital-Internal Medicine ( Site 0403)

    Tainan, 704

  • National Taiwan University Hospital ( Site 0400)

    Taipei, 10002

  • Taipei Veterans General Hospital-Department of Medicine ( Site 0402)

    Taipei, 11217

  • Chang Gung Medical Foundation-Linkou Branch ( Site 0404)

    Taoyuan, 33305

Other trials in Taiwan

Argentina3 sites

  • CIPREC-CIPREC Sede Arenales ( Site 1000)

    Buenos Aires, Buenos Aires F.D., C1061AAS

  • Instituto de Investigaciones Clínicas Mar del Plata ( Site 1002)

    Mar del Plata, Buenos Aires, B7600FZO

  • Fundacion Estudios Clinicos ( Site 1001)

    Rosario, Santa Fe Province, S2000DEJ

Other trials in Argentina

United Kingdom3 sites

  • Barts Health NHS Trust-William Harvey Clinical Research Centre ( Site 0901)

    London, England, EC1M 6BQ

  • Royal Free Hospital ( Site 0900)

    London, England, NW3 2QG

  • National Institute for Health Research UCLH Clinical Research Facility ( Site 0908)

    London, London, City of, NW1 2PG

Other trials in United Kingdom

About this study

Official title: A Phase 3, Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of MK-0616 Compared With Ezetimibe or Bempedoic Acid or Ezetimibe and Bempedoic Acid in Adults With Hypercholesterolemia

The main purpose of this study is to assess whether enlicitide is superior to ezetimibe or bempedoic acid or ezetimibe + bempedoic acid in reducing low-density lipoprotein cholesterol (LDL-C) in participants with hypercholesterolemia, and to evaluate its safety and tolerability. The primary study hypotheses are enlicitide is superior to ezetimibe, bempedoic acid, and ezetimibe + bempedoic acid on mean percent change from baseline in LDL-C at week 8.

Being tested
Enlicitide, Ezetimibe, Bempedoic Acid, Placebo for Enlicitide, Placebo for Ezetimibe
Medical subject headings
Hypercholesterolemia

What participants receive

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

  • EnlicitideDrug

    Also called MK-0616, Enlicitide Decanoate

    Oral tablet

  • EzetimibeDrug

    Oral tablet

  • Bempedoic AcidDrug

    Oral capsule

  • Placebo for EnlicitideOther

    enlicitide-matching placebo oral tablet

  • Placebo for EzetimibeOther

    ezetimibe-matching placebo oral tablet

  • Placebo for Bempedoic AcidOther

    bempedoic acid-matching placebo oral capsule

Study groups in NCT06450366
Study groupRoleWhat they receive
EnlicitideExperimentalParticipants receive enlicitide 20mg, ezetimibe-matching placebo, and bempedoic acid-matching placebo once daily (QD) orally up to approximately 56 days.
Receives: Drug: Enlicitide; Other: Placebo for Ezetimibe; Other: Placebo for Bempedoic Acid
EzetimibeActive comparatorParticipants receive ezetimibe 10mg, enlicitide-matching placebo, and bempedoic acid-matching placebo QD orally up to approximately 56 days.
Receives: Drug: Ezetimibe; Other: Placebo for Enlicitide; Other: Placebo for Bempedoic Acid
Bempedoic AcidActive comparatorParticipants receive bempedoic acid 180mg, ezetimibe-matching placebo, and enlicitide-matching placebo QD orally up to approximately 56 days.
Receives: Drug: Bempedoic Acid; Other: Placebo for Enlicitide; Other: Placebo for Ezetimibe
Ezetimibe + Bempedoic AcidActive comparatorParticipants receive ezetimibe 10 mg, bempedoic acid 180mg, enlicitide-matching placebo orally QD for approximately 56 days.
Receives: Drug: Ezetimibe; Drug: Bempedoic Acid; Other: Placebo for Enlicitide

What is being measured

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

  1. Mean Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Day 56

    Blood samples were collected at baseline and after 56 days of treatment to assess mean percentage change in LDL-C. The mean percent change from baseline in LDL-C at Day-56 is reported.

    Measured: Baseline and Day 56

Secondary outcomes (7)

  1. Mean Percent Change From Baseline in Apolipoprotein B (ApoB) at Day 56

    Blood samples were collected at baseline and on day 56 of treatment to assess mean percent change in ApoB. The mean percent change from baseline in ApoB at Day 56 is reported.

    Measured: Baseline and Day 56

  2. Mean Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Day 56

    Blood samples were collected at baseline and on day 56 of treatment to assess mean percent change in non-HDL-C. The mean percent change from baseline in non-HDL-C at 56 days is reported.

    Measured: Baseline and Day 56

  3. Median Percent Change From Baseline in Lipoprotein(a) Levels (Lp[a])

    Blood samples were collected at baseline and on day 56 of treatment to assess median percent change in Lp(a) levels. The median percent change from baseline at Day 56 is reported.

    Measured: Baseline and Day 56

  4. Percentage of Participants Who at Day 56 Have an LDL-C <70 mg/dL and ≥50% Reduction From Baseline

    Blood samples were collected at baseline and after 56 days of treatment to assess the percentage of participants who have an LDL-C <70 mg/dL and ≥50% reduction from baseline at day 56. The percentage of participants who have LDL-C <70 mg/dL and ≥50% reduction from baseline is reported.

    Measured: Baseline and Day 56

  5. Percentage of Participants Who at Day 56 Have an LDL-C <55 mg/dL and ≥50% Reduction From Baseline

    Blood samples were collected at baseline and after 56 days of treatment to assess the percentage of participants who have an LDL-C <55 mg/dL and ≥50% reduction from baseline at day 56. The percentage of participants who have LDL-C <55 mg/dL and ≥50% reduction from baseline is reported.

    Measured: Baseline and Day 56

  6. Percentage of Participants With ≥1 Adverse Event (AE)

    An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who experienced an AE is reported.

    Measured: Up to approximately 147 days

  7. Percentage of Participants Discontinuing From Study Intervention Due to AE

    An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinued study intervention due to an AE is reported.

    Measured: Up to approximately 91 days

Timeline

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

  1. First posted10 Jun 2024
  2. Study start8 Jul 2024
  3. Primary completion14 Feb 2025
  4. Study completion28 Mar 2025

Resources

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
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
301 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06450366
Sponsor's protocol ID
0616-018
Other IDs
MK-0616-018, 2023-504920-25-00, U1111-1290-3888, 2023
Status last verified
Mar 2026
First submitted
4 Jun 2024
Last updated
27 Mar 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

  • Catapano AL, Mikhailova E, Navar AM, Banka P, Corral P, Saxena M, Steg PG, Verma S, Kordahi AY, Mendizabal G, Zhu P, Ballantyne CM; CORALreef AddOn Investigators. Oral PCSK9 Inhibitor Enlicitide Versus Oral Nonstatin Therapies: A Phase 3 Randomized Clinical Trial. J Am Coll Cardiol. 2026 Jul 21;88(3):340-352. doi: 10.1016/j.jacc.2026.03.036. Epub 2026 Mar 30.

    PubMed 42017875

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Enlicitide, Ezetimibe and Bempedoic Acid in people with Hypercholesterolemia, run by Merck Sharp & Dohme LLC at 35 sites in 8 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 5 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 27 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 35 sites in United States, Canada, Spain, France, Israel and 3 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. 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 27 Mar 2026). 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?

Mean Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Day 56 (time frame: Baseline and Day 56). 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 NCT06450366, 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 27 Mar 2026.

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