A Study to Evaluate the Efficacy and Safety of Enlicitide Decanoate (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

Phase 3

Active, not recruiting

• Conditions: Hypercholesterolemia
• Interventions: Drug: Ezetimibe; Drug: Bempedoic Acid; Drug: Enlicitide Decanoate; Other: Placebo for Ezetimibe; Other: Placebo for Enlicitide Decanoate; Other: Placebo for Bempedoic Acid

• Registration Number: NCT06450366
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-06-04
• Study First Submitted QC: 2024-06-04
• Study First Posted: 2024-06-10
• Study Start: 2024-07-08
• Status Verified: 2025-02
• Primary Completion: 2025-02-14
• Last Update Submitted: 2025-02-24
• Last Update Posted: 2025-02-26
• Study Completion: 2025-04-28

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 301

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 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Enlicitide Decanoate	Placebo for Ezetimibe	Participants receive enlicitide decanoate 20mg, ezetimibe-matching placebo, and bempedoic acid-matching placebo once daily (QD) orally up to approximately 56 days.
Enlicitide Decanoate	Placebo for Bempedoic Acid	Participants receive enlicitide decanoate 20mg, ezetimibe-matching placebo, and bempedoic acid-matching placebo once daily (QD) orally up to approximately 56 days.
Ezetimibe	Ezetimibe	Participants receive ezetimibe 10mg, enlicitide decanoate-matching placebo, and bempedoic acid-matching placebo QD orally up to approximately 56 days.
Ezetimibe	Placebo for Enlicitide Decanoate	Participants receive ezetimibe 10mg, enlicitide decanoate-matching placebo, and bempedoic acid-matching placebo QD orally up to approximately 56 days.
Ezetimibe	Placebo for Bempedoic Acid	Participants receive ezetimibe 10mg, enlicitide decanoate-matching placebo, and bempedoic acid-matching placebo QD orally up to approximately 56 days.
Bempedoic Acid	Bempedoic Acid	Participants receive bempedoic acid 180mg, ezetimibe-matching placebo, and enlicitide decanoate-matching placebo QD orally up to approximately 56 days.
Bempedoic Acid	Placebo for Enlicitide Decanoate	Participants receive bempedoic acid 180mg, ezetimibe-matching placebo, and enlicitide decanoate-matching placebo QD orally up to approximately 56 days.
Bempedoic Acid	Placebo for Ezetimibe	Participants receive bempedoic acid 180mg, ezetimibe-matching placebo, and enlicitide decanoate-matching placebo QD orally up to approximately 56 days.
Ezetimibe + Bempedoic Acid	Ezetimibe	Participants receive ezetimibe 10 mg, bempedoic acid 180mg, enlicitide decanoate-matching placebo orally QD for approximately 56 days.
Ezetimibe + Bempedoic Acid	Bempedoic Acid	Participants receive ezetimibe 10 mg, bempedoic acid 180mg, enlicitide decanoate-matching placebo orally QD for approximately 56 days.
Ezetimibe + Bempedoic Acid	Placebo for Enlicitide Decanoate	Participants receive ezetimibe 10 mg, bempedoic acid 180mg, enlicitide decanoate-matching placebo orally QD for approximately 56 days.
Enlicitide Decanoate	Enlicitide Decanoate	Participants receive enlicitide decanoate 20mg, ezetimibe-matching placebo, and bempedoic acid-matching placebo once daily (QD) orally up to approximately 56 days.

Primary Outcome Measures

Name	Time	Method
Mean Percent Change from Baseline in LDL-C at Day 56	Baseline and Day 56	Blood samples will be collected at baseline and after 56 days of treatment to assess mean percentage change in LDL-C. The percent change from baseline in LDL-C at Day-56 will be reported.

Secondary Outcome Measures

Name	Time	Method
Mean Percent Change from Baseline in Apolipoprotein B (ApoB) at Day 56	Baseline and Day 56	Blood samples will be collected at baseline and on day 56 of treatment to assess mean percent change in ApoB. The percent change from baseline in ApoB at Day 56 will be reported.
Mean Percent Change from Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Day 56	Baseline and Day 56	Blood samples will be collected at baseline and on day 56 of treatment to assess mean percent change in non-HDL-C. The percent change from baseline in non-HDL-C at 56 days will be reported.
Percentage of Participants Who at Day 56 Have an LDL-C <70 mg/dL and ≥50% Reduction from Baseline	Baseline and Day 56	The percentage of participants who have an LDL-C \<70 mg/dL and \>50% reduction from baseline at day 56 will be reported.
Percentage of Participants Who at Day 56 Have an LDL-C <55 mg/dL and ≥50% Reduction from Baseline	Baseline and Day 56	The percentage of participants who have an LDL-C \<55 mg/dL and \>50% reduction from baseline at day 56 will be reported.
Number of Participants With ≥1 Adverse Event (AE)	Up to Approximately 112 days	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.
Percent Change from Baseline in Lipoprotein(a) Levels (Lp[a])	Baseline and Day 56	Blood samples will be collected at baseline and on day 56 of treatment to assess percent change in Lp(a) levels. The change from baseline at Day 56 will be reported.
Number of Participants Discontinuing from Study Therapy Due to AE	Up to Approximately 56 days	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.

Trial Locations

Locations (35)

Clinical Trials Research ( Site 1509); 🇺🇸 Lincoln, California, United States

Velocity Clinical Research Rockville ( Site 1503); 🇺🇸 Rockville, Maryland, United States

Rainier Clinical Research Center ( Site 1502); 🇺🇸 Renton, Washington, United States

Healthcare Research Network - Chicago ( Site 1507); 🇺🇸 Flossmoor, Illinois, United States

North York Diagnostic and Cardiac Centre ( Site 1605); 🇨🇦 North York, Ontario, Canada

Institut de Cardiologie de Montreal ( Site 1604); 🇨🇦 Montreal, Quebec, Canada

Diex Recherche Trois-Rivieres ( Site 1602); 🇨🇦 Trois-Rivieres, Quebec, Canada

L-MARC Research Center ( Site 1501); 🇺🇸 Louisville, Kentucky, United States

Velocity Clinical Research, Gulfport ( Site 1505); 🇺🇸 Gulfport, Mississippi, United States

Piedmont Research Partners ( Site 1506); 🇺🇸 Fort Mill, South Carolina, United States

Instituto de Investigaciones Clínicas Mar del Plata ( Site 1002); 🇦🇷 Mar del Plata, Buenos Aires, Argentina

CIPREC-CIPREC Sede Arenales ( Site 1000); 🇦🇷 Buenos Aires, Caba, Argentina

Cambridge Cardiac Care Centre ( Site 1603); 🇨🇦 Cambridge, Ontario, Canada

Hôpital Arnaud de Villeneuve - CHU Montpellier ( Site 0505); 🇫🇷 Montpellier, Herault, France

Fundacion Estudios Clinicos ( Site 1001); 🇦🇷 Rosario, Santa Fe, Argentina

The Medical Arts Health Research Group ( Site 1606); 🇨🇦 Vancouver, British Columbia, Canada

Hôpital Nord Guillaume-et-René-Laennec / CHU de Nantes-CIC Endocrinology-Diabetology-Nutrition ( Sit; 🇫🇷 Nantes Cedex 1, Loire-Atlantique, France

Hospices Civils de Lyon - Hopital Louis Pradel ( Site 0501); 🇫🇷 Bron, Rhone, France

Hôpital Bichat - Claude-Bernard ( Site 0504); 🇫🇷 Paris, France

Assuta Beersheba MC ( Site 0704); 🇮🇱 Be Er Sheva, Israel

Yitzhak Shamir Medical Center. ( Site 0702); 🇮🇱 Beer Yaakov, Israel

Rambam Health Care Campus ( Site 0700); 🇮🇱 Haifa, Israel

Meir Medical Center. ( Site 0703); 🇮🇱 Kfar Saba, Israel

Hospital Universitario Virgen de la Victoria-UGC Endocrinologia y nutricion ( Site 0801); 🇪🇸 Malaga, Andalucia, Spain

Hospital de Figueres ( Site 0804); 🇪🇸 Figueres, Gerona, Spain

Hospital San Rafael de Coruna ( Site 0805); 🇪🇸 A Coruna, La Coruna, Spain

EAP Sardenya ( Site 0800); 🇪🇸 Barcelona, Spain

Hospital Universitari Vall d'Hebron ( Site 0803); 🇪🇸 Barcelona, Spain

National Cheng Kung University Hospital-Internal Medicine ( Site 0403); 🇨🇳 Tainan, Taiwan

National Taiwan University Hospital ( Site 0400); 🇨🇳 Taipei, Taiwan

Taipei Veterans General Hospital-Department of Medicine ( Site 0402); 🇨🇳 Taipei, Taiwan

Chang Gung Medical Foundation-Linkou Branch ( Site 0404); 🇨🇳 Taoyuan, Taiwan

Barts Health NHS Trust-William Harvey Clinical Research Centre ( Site 0901); 🇬🇧 London, England, United Kingdom

Royal Free Hospital ( Site 0900); 🇬🇧 London, England, United Kingdom

National Institute for Health Research UCLH Clinical Research Facility ( Site 0908); 🇬🇧 London, London, City Of, United Kingdom