Phase 3
N=301
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)
Hypercholesterolemia
Bottom Line
View on ClinicalTrials.gov: NCT06450366 ↗Enrolled (actual)
301
Serious AEs
1.7%
Results posted
Mar 2026
Primary outcome: Primary: Mean Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Day 56 — -64.6; -6.3; -27.8; -36.5 Percent Change — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Enlicitide (Drug); Ezetimibe (Drug); Bempedoic Acid (Drug); Placebo for Enlicitide (Other); Placebo for Ezetimibe (Other); Placebo for Bempedoic Acid (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Merck Sharp & Dohme LLC
- Primary completion
- Feb 2025
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Day 56 |
-64.6; -6.3; -27.8; -36.5 | <0.001 sig |
| SECONDARY Mean Percent Change From Baseline in Apolipoprotein B (ApoB) at Day 56 |
-54.6; -5.4; -20.2; -27.7 | <0.001 sig |
| SECONDARY Mean Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Day 56 |
-58.0; -5.2; -25.1; -31.8 | <0.001 sig |
| SECONDARY Median Percent Change From Baseline in Lipoprotein(a) Levels (Lp[a]) |
-26.2; 8.1; 0.0; 10.4 | — |
| SECONDARY Percentage of Participants Who at Day 56 Have an LDL-C <70 mg/dL and ≥50% Reduction From Baseline |
81.2; 2.0; 8.0; 22.0 | — |
| SECONDARY Percentage of Participants Who at Day 56 Have an LDL-C <55 mg/dL and ≥50% Reduction From Baseline |
78.2; 2.0; 8.0; 20.0 | — |
| SECONDARY Percentage of Participants With ≥1 Adverse Event (AE) |
39.6; 38.0; 36.0; 45.0 | — |
| SECONDARY Percentage of Participants Discontinuing From Study Intervention Due to AE |
2.0; 4.0; 0.0; 4.0 | — |
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. 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.
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT06450366). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.