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

Merck Sharp & Dohme (MSD)

Status and phase: Active, not recruiting; Phase 3

Conditions: Hypercholesterolemia

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT06450366

2023-504920-25 (Registry Identifier)

U1111-1290-3888 (Other Identifier)

MK-0616-018 (Other Identifier)

0616-018

Details and patient eligibility

About

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.

Enrollment: 301 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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301 participants in 4 patient groups

Enlicitide Decanoate

Experimental group

Description:

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

Treatment:

Other: Placebo for Ezetimibe

Other: Placebo for Bempedoic Acid

Drug: Enlicitide Decanoate

Ezetimibe

Active Comparator group

Description:

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

Treatment:

Other: Placebo for Enlicitide Decanoate

Other: Placebo for Bempedoic Acid

Drug: Ezetimibe

Bempedoic Acid

Active Comparator group

Description:

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

Treatment:

Other: Placebo for Enlicitide Decanoate

Other: Placebo for Ezetimibe

Drug: Bempedoic Acid

Ezetimibe + Bempedoic Acid

Active Comparator group

Description:

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

Treatment:

Other: Placebo for Enlicitide Decanoate

Drug: Bempedoic Acid

Drug: Ezetimibe