Primary outcomeMean· Baseline and Day 56
Mean Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Day 56
| Group | Value (Percent Change) |
|---|---|
| Enlicitide | -64.6 |
| Bempedoic Acid | -6.3 |
| Ezetimibe | -27.8 |
| Ezetimibe + Bempedoic Acid | -36.5 |
Trial · Interventional
CompletedPhase 3Results postedRegistry dataA 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)
NCTNCT06450366 (opens ClinicalTrials.gov in a new tab)Other id0616-018Other idMK-0616-018Other id2023-504920-25-00Other idU1111-1290-3888
Overview
- Status
- Completed
- Phase
- Phase 3
- Enrollment
- 301 participants (actual)
- Sponsor
- Merck Sharp & Dohme LLC · Industry
- Design
- Randomized · Triple masking
- Countries
8 countries
United States, Argentina, Canada, France, Israel, Spain, Taiwan, United Kingdom
- Start
- 8 Jul 2024
- Primary completion
- 14 Feb 2025
- Completion
- 28 Mar 2025
- First posted
- 10 Jun 2024
- Last update posted
- 27 Mar 2026
- Conditions
- Hypercholesterolemia
Timeline
1 trial · 1 completed · 1 with posted results
- Completed
- Ongoing
- Not yet recruiting
- Stopped
- Estimated dates (est.)
- Results posted
202420252026
- Ph 3
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)
NCT064503668 Jul 2024 to 28 Mar 2025
Registry summary
Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.
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.
Interventions
- EnlicitideDrug
- EzetimibeDrug
- Bempedoic AcidDrug
- Placebo for EnlicitideOther
- Placebo for EzetimibeOther
- Placebo for Bempedoic AcidOther
Arms4
Experimental
Enlicitide
Participants receive enlicitide 20mg, ezetimibe-matching placebo, and bempedoic acid-matching placebo once daily (QD) orally up to approximately 56 days.
Active comparator
Ezetimibe
Participants receive ezetimibe 10mg, enlicitide-matching placebo, and bempedoic acid-matching placebo QD orally up to approximately 56 days.
Active comparator
Bempedoic Acid
Participants receive bempedoic acid 180mg, ezetimibe-matching placebo, and enlicitide-matching placebo QD orally up to approximately 56 days.
Active comparator
Ezetimibe + Bempedoic Acid
Participants receive ezetimibe 10 mg, bempedoic acid 180mg, enlicitide-matching placebo orally QD for approximately 56 days.
Primary outcomes1
Outcomes the sponsor listed as primary.
Mean Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Day 56
Time frame · Baseline and Day 56
Registry description
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.
Secondary outcomes(7)
Mean Percent Change From Baseline in Apolipoprotein B (ApoB) at Day 56
Time frame · Baseline and Day 56
Registry description
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.
Mean Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Day 56
Time frame · Baseline and Day 56
Registry description
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.
Median Percent Change From Baseline in Lipoprotein(a) Levels (Lp[a])
Time frame · Baseline and Day 56
Registry description
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.
Percentage of Participants Who at Day 56 Have an LDL-C <70 mg/dL and ≥50% Reduction From Baseline
Time frame · Baseline and Day 56
Registry description
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.
Percentage of Participants Who at Day 56 Have an LDL-C <55 mg/dL and ≥50% Reduction From Baseline
Time frame · Baseline and Day 56
Registry description
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.
Percentage of Participants With ≥1 Adverse Event (AE)
Time frame · Up to approximately 147 days
Registry description
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.
Percentage of Participants Discontinuing From Study Intervention Due to AE
Time frame · Up to approximately 91 days
Registry description
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.
Posted results
Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.
Primary outcome results
Secondary and other outcome results(7)
Secondary outcomeMean· Baseline and Day 56
Mean Percent Change From Baseline in Apolipoprotein B (ApoB) at Day 56
| Group | Value (Percent Change) |
|---|---|
| Enlicitide | -54.6 |
| Bempedoic Acid | -5.4 |
| Ezetimibe | -20.2 |
| Ezetimibe + Bempedoic Acid | -27.7 |
Secondary outcomeMean· Baseline and Day 56
Mean Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Day 56
| Group | Value (Percent Change) |
|---|---|
| Enlicitide | -58.0 |
| Bempedoic Acid | -5.2 |
| Ezetimibe | -25.1 |
| Ezetimibe + Bempedoic Acid | -31.8 |
Secondary outcomeMedian· Baseline and Day 56
Median Percent Change From Baseline in Lipoprotein(a) Levels (Lp[a])
| Group | Value (Percent Change) |
|---|---|
| Enlicitide | -26.2 |
| Bempedoic Acid | 8.1 |
| Ezetimibe | 0.0 |
| Ezetimibe + Bempedoic Acid | 10.4 |
Secondary outcomeNumber· Baseline and Day 56
Percentage of Participants Who at Day 56 Have an LDL-C <70 mg/dL and ≥50% Reduction From Baseline
| Group | Value (Percentage of Participants) |
|---|---|
| Enlicitide | 81.2 |
| Bempedoic Acid | 2.0 |
| Ezetimibe | 8.0 |
| Ezetimibe + Bempedoic Acid | 22.0 |
Secondary outcomeNumber· Baseline and Day 56
Percentage of Participants Who at Day 56 Have an LDL-C <55 mg/dL and ≥50% Reduction From Baseline
| Group | Value (Percentage of participants) |
|---|---|
| Enlicitide | 78.2 |
| Bempedoic Acid | 2.0 |
| Ezetimibe | 8.0 |
| Ezetimibe + Bempedoic Acid | 20.0 |
Secondary outcomeNumber· Up to approximately 147 days
Percentage of Participants With ≥1 Adverse Event (AE)
| Group | Value (Percentage of Participants) |
|---|---|
| Enlicitide | 39.6 |
| Bempedoic Acid | 38.0 |
| Ezetimibe | 36.0 |
| Ezetimibe + Bempedoic Acid | 45.0 |
Secondary outcomeNumber· Up to approximately 91 days
Percentage of Participants Discontinuing From Study Intervention Due to AE
| Group | Value (Percentage of participants) |
|---|---|
| Enlicitide | 2.0 |
| Bempedoic Acid | 4.0 |
| Ezetimibe | 0.0 |
| Ezetimibe + Bempedoic Acid | 4.0 |
Adverse events, as posted
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| Enlicitide 20 mgParticipants receive enlicitide 20mg, ezetimibe-matching placebo, and bempedoic acid-matching placebo once daily (QD) orally up to approximately 56 days. | 0 / 101 | 0 / 101 | 0 / 101 |
| Bempedoic Acid 180 mgParticipants receive bempedoic acid 180mg, ezetimibe-matching placebo, and enlicitide-matching placebo QD orally up to approximately 56 days. | 0 / 50 | 4 / 50 | 3 / 50 |
| Ezetimibe 10 mgParticipants receive ezetimibe 10mg, enlicitide-matching placebo, and bempedoic acid-matching placebo QD orally up to approximately 56 days. | 0 / 50 | 1 / 50 | 3 / 50 |
| Ezetimibe 10 mg and Bempedoic Acid 180 mgParticipants receive ezetimibe 10 mg, bempedoic acid 180mg, enlicitide-matching placebo orally QD for approximately 56 days. | 0 / 100 | 0 / 100 | 0 / 100 |
Each cell reads participants affected / participants at risk, as the registry posted them.
Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works
Studies1
Studies that cite this trial.
Studies with results
1 study on this page
Indexing hint: Randomized controlled trial · 2026
11 results
Oral PCSK9 Inhibitor Enlicitide Versus Oral Nonstatin Therapies: A Phase 3 Randomized Clinical Trial.
Catapano et al. 2026Journal of the American College of Cardiologycited by 10
PMID 42017875DOI 10.1016/j.jacc.2026.03.036PUB-42017875
Full text at the publisher11 results
Eligibility
Who could join, as posted.
- Sex
- All
- Age
- from 18 Years
- Healthy volunteers
- Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria:
* 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
Exclusion Criteria:
* 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
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