MK-0616 for High Cholesterol

Not currently recruiting at 807 trial locations

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Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Statins

Must not be taking: PCSK9 inhibitors

Disqualifiers: Heart failure, Ventricular tachycardia, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 6 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new oral medication, enlicitide decanoate (also known as MK-0616), to determine its effectiveness in preventing major heart-related problems, such as heart attacks or strokes, in individuals with high cholesterol and a high risk of heart issues. Participants will receive either the medication or a placebo to compare effects. Suitable candidates have had heart-related procedures or conditions like a heart attack or stroke, or are at high risk for such events, and are already on cholesterol-lowering treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in heart health.

Will I have to stop taking my current medications?

The trial requires that you stay on a stable dose of your current cholesterol-lowering medications, including statins, for at least 30 days before starting and throughout the study. No changes to your medication or dose are planned during the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that enlicitide decanoate, also known as MK-0616, is generally well-tolerated. Earlier studies found this treatment significantly lowers LDL-C, often referred to as "bad cholesterol." This indicates promising effectiveness and safety. Participants in these studies did not report any major safety issues.

While any treatment carries some risks, enlicitide decanoate's progression to a phase 3 trial indicates it has passed earlier testing stages. These tests help ensure the treatment's safety for larger groups. Although no treatment can be guaranteed to be 100% safe for everyone, the data so far appears reassuring for enlicitide decanoate. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for high cholesterol?

Unlike the standard treatments for high cholesterol, which typically include statins like atorvastatin or rosuvastatin, MK-0616 introduces a novel approach by using enlicitide decanoate. This treatment is unique because it is a peptide-based drug, which might offer a new mechanism of action by targeting cholesterol metabolism differently than traditional statins. Researchers are excited about MK-0616 as it has the potential to provide an effective alternative for patients who cannot tolerate statins due to side effects, potentially offering similar or improved cholesterol-lowering effects with fewer adverse reactions.

What evidence suggests that MK-0616 might be an effective treatment for high cholesterol?

Studies have shown that enlicitide decanoate, an oral medication, can significantly lower LDL cholesterol, often called "bad" cholesterol. One study found that patients taking enlicitide decanoate experienced up to a 60.9% reduction in LDL levels. Lower LDL cholesterol is important because it is linked to fewer heart problems. Additionally, earlier research found that enlicitide decanoate led to meaningful improvements in cholesterol levels in people with high cholesterol. In this trial, participants will receive either enlicitide decanoate or a placebo. These findings suggest that enlicitide decanoate could effectively reduce the risk of major heart-related events. ^{1 2 3 4 5}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for adults at high risk of a major cardiovascular event who have had one before. They must be on stable cholesterol-lowering meds, including statins, and not planning changes during the study. People with very high triglycerides, recent severe heart issues, certain genetic cholesterol disorders, or severe kidney disease can't join.

Inclusion Criteria

I am currently taking strong cholesterol medication.

I have been on the same dose of my long-term treatments for over 30 days.

You have a high risk of experiencing a major heart or blood vessel problem for the first time.

Exclusion Criteria

I have a genetic condition that causes very high cholesterol.

I have taken or am taking certain cholesterol medications without a break.

I have severe kidney problems or am on dialysis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive enlicitide decanoate 20 mg or placebo once daily

Up to 6 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MK-0616

Trial Overview

The study tests MK-0616, an oral drug aiming to prevent major heart-related events by inhibiting PCSK9 versus a placebo. Participants are randomly assigned to either receive MK-0616 or a placebo to see if it extends the time until another serious heart issue occurs.

How Is the Trial Designed?

Group I: Enlicitide Decanoate Experimental Treatment 1 Intervention

Participants receive enlicitide decanoate 20 mg once daily.

Group II: Placebo Placebo Group 1 Intervention

Participants receive placebo once daily.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

Dietary therapy is the first line of treatment for dyslipidaemia, and lipid-lowering medications are recommended for patients who do not respond adequately to diet, especially those with coronary heart disease (CHD) or multiple risk factors.

Statins are highlighted for their antiatherosclerotic properties, making them a key choice among various lipid-lowering drugs, which also include anion-exchange resins, fibrates, and newer experimental classes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacologic treatment of lipid metabolism disorders]. Gmiński, J.[2010]

Intensive reduction of low-density lipoprotein cholesterol (LDL-C) is crucial for lowering the risk of coronary heart disease (CHD), with new guidelines suggesting targets of 2 mmol/L for LDL-C, which may lead to better treatment outcomes for patients.

Statins, particularly rosuvastatin, have shown significant efficacy in reducing LDL-C levels (up to 55%) and improving clinical outcomes in high-risk patients, while ongoing studies aim to further clarify the optimal LDL-C levels for risk reduction and the importance of raising high-density lipoprotein cholesterol (HDL-C) as a therapeutic target.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical lipid-regulating therapy: current evidence, ongoing trials and future developments. Evans, M., Roberts, A., Davies, S., et al.[2022]

Raising high-density lipoprotein cholesterol (HDLC) in patients with low levels is considered in high-risk individuals, such as those with established heart disease or diabetes, but there is still uncertainty about the benefits of HDL-raising therapies due to a lack of event-based trials.

In high-risk patients, statins are typically used to lower low-density lipoprotein cholesterol (LDLC), and additional medications like niacin or fibrates may be added to effectively raise HDLC levels, although specific HDLC targets are not formally established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Drug Options for Raising HDL Cholesterol. Dunbar, RL., Rader, DJ.[2020]

Fenofibrate therapy in a study of 9795 patients showed an 11% reduction in coronary events, particularly benefiting primary prevention and nonfatal myocardial events, although the results were confounded by statin use.

Fenofibrate demonstrated good safety profiles, even when combined with statins, but raised old concerns about risks like sudden death and pancreatitis; it also showed unexpected benefits in reducing microvascular complications such as microalbuminuria and retinopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FIELDS of dreams, fields of tears: a perspective on the fibrate trials. Wierzbicki, AS.[2013]

New drug therapies targeting multiple cardiometabolic risk factors for metabolic syndrome have shown promise, including agents that improve HDL cholesterol levels and glucose metabolism, which are crucial for reducing coronary heart disease risk.

Clinical trials indicate that therapies like cholesteryl ester transfer protein inhibitors and glitazars not only enhance lipid profiles but also address abnormal glucose metabolism, highlighting their potential in comprehensive cardiovascular risk management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New and emerging strategies for reducing cardiometabolic risk factors. Rodgers, PT., Fuke, DC.[2017]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05261126

A Study of the Efficacy and Safety of Enclitide Chloride (MK ...

A Study of the Efficacy and Safety of Enclitide Chloride (MK-0616 Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-008). ClinicalTrials.gov ...

2.

merck.com

merck.com/news/merck-announces-positive-topline-results-from-the-first-two-phase-3-coralreef-trials-evaluating-enlicitide-decanoate-for-the-treatment-of-adults-with-hyperlipidemia/

Merck Announces Positive Topline Results From the First ...

Enlicitide demonstrated statistically significant and clinically meaningful reductions in LDL-C in both Phase 3 CORALreef HeFH and CORALreef AddOn trials.

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11722601/

Emerging oral therapeutic strategies for inhibiting PCSK9

At 8 week follow-up, enlicitide decanoate reduced, in a dose dependent manner, LDL cholesterol by −41.2 %, −55.7 %, −59.1 %, and −60.9 % after oral ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06008756

Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor ...

This is a phase 3, randomized, placebo-controlled study of the efficacy and safety of enlicitide decanoate, an oral proprotein convertase subtilisin/kexin ...

5.

clinicaltrials.eu

clinicaltrials.eu/trial/study-on-the-effectiveness-and-safety-of-mk-0616-for-adults-with-high-cholesterol/

Study on the Effectiveness and Safety of MK-0616 for ...

The study aims to provide valuable information on whether MK-0616 can effectively lower cholesterol levels and improve heart health in individuals with ...