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)

NCT06450366 | Completed Phase 3 Results DMC FDA Drug

• 4 other identifiers: 0616-018MK-0616-0182023-504920-25-00U1111-1290-3888
• Study Type: interventional
• Target: 301
• Locations: 8 countries
• Sites: 35

Brief 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.

Conditions

Hypercholesterolemia

Outcome Measures

Primary Outcomes (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.

  Baseline and Day 56

Secondary Outcomes (7)

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

  Baseline and Day 56

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

  Baseline and Day 56

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

  Baseline and Day 56

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

  Baseline and Day 56

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

  Baseline and Day 56

Study Arms (4)

Enlicitide

EXPERIMENTAL

Participants receive enlicitide 20mg, ezetimibe-matching placebo, and bempedoic acid-matching placebo once daily (QD) orally up to approximately 56 days.

Drug: Enlicitide; Other: Placebo for Ezetimibe; Other: Placebo for Bempedoic Acid

Ezetimibe

ACTIVE COMPARATOR

Participants receive ezetimibe 10mg, enlicitide-matching placebo, and bempedoic acid-matching placebo QD orally up to approximately 56 days.

Drug: Ezetimibe; Other: Placebo for Enlicitide; Other: Placebo for Bempedoic Acid

Bempedoic Acid

ACTIVE COMPARATOR

Participants receive bempedoic acid 180mg, ezetimibe-matching placebo, and enlicitide-matching placebo QD orally up to approximately 56 days.

Drug: Bempedoic Acid; Other: Placebo for Enlicitide; Other: Placebo for Ezetimibe

Ezetimibe + Bempedoic Acid

ACTIVE COMPARATOR

Participants receive ezetimibe 10 mg, bempedoic acid 180mg, enlicitide-matching placebo orally QD for approximately 56 days.

Drug: Ezetimibe; Drug: Bempedoic Acid; Other: Placebo for Enlicitide

Interventions

Ezetimibe DRUG

Oral tablet

Ezetimibe; Ezetimibe + Bempedoic Acid

Bempedoic Acid DRUG

Oral capsule

Bempedoic Acid; Ezetimibe + Bempedoic Acid

Enlicitide DRUG

Oral tablet

Also known as: MK-0616, Enlicitide Decanoate

Enlicitide

Placebo for Enlicitide OTHER

enlicitide-matching placebo oral tablet

Bempedoic Acid; Ezetimibe; Ezetimibe + Bempedoic Acid

Placebo for Ezetimibe OTHER

ezetimibe-matching placebo oral tablet

Bempedoic Acid; Enlicitide

Placebo for Bempedoic Acid OTHER

bempedoic acid-matching placebo oral capsule

Enlicitide; Ezetimibe

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (35)

Clinical Trials Research ( Site 1509)

Lincoln, California, 95648, United States

Location

Healthcare Research Network - Chicago ( Site 1507)

Flossmoor, Illinois, 60422, United States

Location

L-MARC Research Center ( Site 1501)

Louisville, Kentucky, 40213, United States

Location

Velocity Clinical Research Rockville ( Site 1503)

Rockville, Maryland, 20854, United States

Location

Velocity Clinical Research, Gulfport ( Site 1505)

Gulfport, Mississippi, 39503, United States

Location

Piedmont Research Partners ( Site 1506)

Fort Mill, South Carolina, 29707, United States

Location

Rainier Clinical Research Center ( Site 1502)

Renton, Washington, 98057, United States

Location

Instituto de Investigaciones Clínicas Mar del Plata ( Site 1002)

Mar del Plata, Buenos Aires, B7600FZO, Argentina

Location

CIPREC-CIPREC Sede Arenales ( Site 1000)

Buenos Aires, Buenos Aires F.D., C1061AAS, Argentina

Location

Fundacion Estudios Clinicos ( Site 1001)

Rosario, Santa Fe Province, S2000DEJ, Argentina

Location

The Medical Arts Health Research Group ( Site 1606)

Vancouver, British Columbia, V7M 2H4, Canada

Location

Cambridge Cardiac Care Centre ( Site 1603)

Cambridge, Ontario, N1R 6V6, Canada

Location

North York Diagnostic and Cardiac Centre ( Site 1605)

North York, Ontario, M6B 3H7, Canada

Location

Institut de Cardiologie de Montreal ( Site 1604)

Montreal, Quebec, H1T 1C8, Canada

Location

Diex Recherche Trois-Rivieres ( Site 1602)

Trois-Rivières, Quebec, G9A 4P3, Canada

Location

Hôpital Arnaud de Villeneuve - CHU Montpellier ( Site 0505)

Montpellier, Herault, 34090, France

Location

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

Nantes, Loire-Atlantique, 44093, France

Location

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

Bron, Rhone, 69677, France

Location

Hôpital Bichat - Claude-Bernard ( Site 0504)

Paris, 75018, France

Location

Yitzhak Shamir Medical Center. ( Site 0702)

Beer Yaakov, 70300, Israel

Location

Assuta Beersheba MC ( Site 0704)

Beersheba, 8489507, Israel

Location

Rambam Health Care Campus ( Site 0700)

Haifa, 3109601, Israel

Location

Meir Medical Center. ( Site 0703)

Kfar Saba, 4428164, Israel

Location

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

Málaga, Andalusia, 29010, Spain

Location

Hospital de Figueres ( Site 0804)

Figueres, Gerona, 17600, Spain

Location

Hospital San Rafael de Coruna ( Site 0805)

A Coruña, La Coruna, 15006, Spain

Location

EAP Sardenya ( Site 0800)

Barcelona, 08025, Spain

Location

Hospital Universitari Vall d'Hebron ( Site 0803)

Barcelona, 08035, Spain

Location

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

Tainan, 704, Taiwan

Location

National Taiwan University Hospital ( Site 0400)

Taipei, 10002, Taiwan

Location

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

Taipei, 11217, Taiwan

Location

Chang Gung Medical Foundation-Linkou Branch ( Site 0404)

Taoyuan District, 33305, Taiwan

Location

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

London, England, EC1M 6BQ, United Kingdom

Location

Royal Free Hospital ( Site 0900)

London, England, NW3 2QG, United Kingdom

Location

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

London, London, City of, NW1 2PG, United Kingdom

Location

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

MK-0616; Ezetimibe; 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2024
• First Posted: June 10, 2024
• Study Start: July 8, 2024
• Primary Completion: February 14, 2025
• Study Completion: March 28, 2025
• Last Updated: March 27, 2026
• Results First Posted: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

GB (3); TW (4); ES (5); US (7); CA (5); FR (4); IL (4); AR (3)