MK-0616 for High Cholesterol

No longer recruiting at 230 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Statins

Must not be taking: PCSK9 inhibitors

Disqualifiers: Homozygous FH, Heart failure, 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: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called enlicitide decanoate (also known as MK-0616) to determine its effectiveness in lowering bad cholesterol (LDL-C) in individuals with high cholesterol. The study compares this treatment to a placebo (a pill with no active medicine) to assess differences in cholesterol levels after 24 weeks. It seeks to determine the treatment's safety and how well participants tolerate it. Suitable candidates include those who have experienced a heart-related event and have high LDL cholesterol or are at risk of such events and currently manage their cholesterol with or without medication. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new cholesterol-lowering treatment.

Will I have to stop taking my current medications?

The trial requires that if you are on any lipid-lowering therapies (medications to lower cholesterol), you should be on a stable dose with no planned changes. If you are taking certain cholesterol-lowering medications like PCSK9 inhibitors, there needs to be an adequate washout period (time without taking these medications) before joining the trial.

Is there any evidence suggesting that MK-0616 is likely to be safe for humans?

Research has shown that enlicitide decanoate, the treatment under study for high cholesterol, has promising safety results. Previous studies found that this treatment effectively lowers LDL cholesterol, known as the "bad" cholesterol, and reported no major safety concerns.

Participants tolerated the treatment well, with no significant side effects directly linked to it, suggesting that enlicitide decanoate is generally safe.

Since this study is in Phase 3, earlier phases have already tested the treatment, closely monitoring its safety. This provides substantial evidence supporting its safety for people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for high cholesterol, which often include statins like atorvastatin or simvastatin, MK-0616 offers a novel approach. Researchers are excited about MK-0616 because it features enlicitide decanoate, a new active ingredient that is taken orally. This treatment could provide a more convenient option, requiring just a simple daily pill. Additionally, it may offer a different mechanism of action that could benefit patients who don't respond well to current therapies.

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

Research has shown that enlicitide decanoate, which participants in this trial may receive, is promising in lowering LDL cholesterol, often called the "bad" cholesterol linked to heart disease. In earlier studies, patients taking enlicitide decanoate experienced up to a 60.9% drop in their LDL levels. This treatment is an oral medication that helps prevent cholesterol buildup in the blood. Other studies have also shown significant reductions in LDL, suggesting it could be a strong option for managing high cholesterol. These results are both statistically significant and clinically meaningful, offering real hope for those with high cholesterol. ^{1 2 3 4 6}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

Adults with high cholesterol are eligible, especially those on stable cholesterol-lowering treatments, with a history of heart issues or at risk for them. LDL-C levels must meet specific criteria. People can't join if they have certain genetic cholesterol disorders, recent heart failure, LDL-C apheresis treatment without proper washout period, or use of some other cholesterol medications.

Inclusion Criteria

I am on a strong statin, have a statin intolerance, or can't take statins.

I am on a stable dose of medication for cholesterol with no changes expected.

I have had a major heart-related event and my bad cholesterol is 55 or higher, or I am at high risk for such an event and my bad cholesterol is 70 or higher.

Exclusion Criteria

I have been hospitalized for heart failure in the last 3 months.

I have taken certain cholesterol medications without a break before starting this trial.

I have a genetic condition that causes very high cholesterol.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive enlicitide decanoate or placebo orally once daily for up to 52 weeks

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MK-0616

Trial Overview The study is testing MK-0616 against a placebo to see if it's better at lowering bad cholesterol (LDL-C) after 24 weeks. Participants will be randomly assigned to either the new oral medication group or the placebo group.

How Is the Trial Designed?

Group I: Enlicitide Decanoate Experimental Treatment 1 Intervention

Participants will receive 20 mg of enlicitide decanoate orally once daily (QD) for up to 52 weeks.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive enlicitide decanoate-matching placebo orally QD for up to 52 weeks.

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

Statins are effective in lowering LDL cholesterol levels and are considered the primary treatment for preventing metabolic disorders and cardiovascular disease, often used in combination with other medications like ezetimibe and bile acid sequestrants.

PCSK9 inhibitors have recently been approved for secondary prevention of cardiovascular disease and are being researched for their role in treating atherogenic dyslipidemia, highlighting the evolving landscape of LDL-C-lowering therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lipid-lowering therapy: Guidelines to precision medicine. Su, X., Cheng, Y., Chang, D.[2022]

Ezetimibe effectively reduces intestinal absorption of cholesterol, leading to a significant decrease in low-density lipoprotein cholesterol (LDLc) by approximately 20-25% at a maximum dose of 40 mg/day, and 16-20% at the common dose of 10 mg/day.

The drug works through a unique mechanism by interfering with the sterol transporter system in intestinal cells, and it can be combined with statins to achieve even greater LDLc reductions of about 25%, while also providing modest increases in high-density lipoprotein cholesterol (HDLc) and reductions in triglycerides.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ezetimibe. Harris, M., Davis, W., Brown, WV.[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]

Cerivastatin significantly reduced low-density lipoprotein cholesterol (LDL-C) levels by 14.2% to 36.1% in a pooled analysis of over 2700 patients, demonstrating its efficacy in treating primary hypercholesterolemia.

The drug was well tolerated, with adverse effects comparable to placebo, and less than 1% of patients experienced significant increases in liver enzymes or muscle enzymes, indicating a strong safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerivastatin in primary hyperlipidemia--a multicenter analysis of efficacy and safety. Stein, E.[2019]

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]

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]

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]

Rosuvastatin, a new statin, has shown significant dose-dependent reductions in LDL cholesterol (LDL-C) ranging from 34% to 65% compared to placebo, indicating its efficacy in lowering cholesterol levels in hypercholesterolemic patients.

In Phase III studies, rosuvastatin was found to be more effective than other commonly used statins like atorvastatin, pravastatin, and simvastatin in improving lipid profiles, suggesting it could be a superior option for patients who struggle to reach target LDL-C levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new statin: a new standard. Olsson, AG.[2023]

Recent research has identified new genetic factors linked to dyslipidemias, such as LDLR-associated protein and proprotein convertase subtilisin-like kexin type 9, which play crucial roles in cholesterol metabolism and could inform future treatments for coronary heart disease (CHD).

While intensive statin therapy can lower LDL cholesterol and potentially reduce cardiovascular risks, it also carries risks of side effects like myopathy and liver damage, highlighting the need for careful consideration of the risk-benefit ratio for individual patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on dyslipidemia. Garg, A., Simha, V.[2007]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05261126

A Study of the Efficacy and Safety of Enclitide Chloride (MK ... The purpose of this study is to evaluate the efficacy and safety of enclitide chloride, an oral PCSK9 inhibitor, in lowering low-density lipoprotein ...

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 ...

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 ...

6. merck.com merck.com/news/mercks-investigational-oral-pcsk9-inhibitor-enlicitide-decanoate-met-all-primary-and-key-secondary-endpoints-in-adults-with-hypercholesterolemia-in-pivotal-coralreef-lipids-study/

Merck's Investigational Oral PCSK9 Inhibitor Enlicitide ... Enlicitide is the first oral PCSK9 inhibitor to demonstrate statistically significant and clinically meaningful reductions in LDL-C compared ...