MK-0616 for High Cholesterol

Recruiting at 176 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

2760 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new medication called MK-0616 to see if it can lower bad cholesterol levels in adults with high cholesterol. The study will compare the effects of MK-0616 over several months. The goal is to find out if MK-0616 is safe, effective, and well-tolerated.

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.

What data supports the effectiveness of the drug MK-0616 for high cholesterol?

The research suggests that lowering LDL cholesterol (bad cholesterol) is beneficial for reducing the risk of heart disease, and drugs like statins are commonly used for this purpose. While specific data on MK-0616 is not provided, similar treatments that lower LDL cholesterol have shown significant benefits in reducing cardiovascular events. ^{1 2 3 4 5}

What makes the drug MK-0616 unique for treating high cholesterol?

The drug MK-0616, also known as Enlicitide, is unique because it represents a novel approach to lowering cholesterol, potentially offering an alternative to traditional statins and other existing treatments like PCSK9 inhibitors. While specific details about its mechanism or administration are not provided, its development suggests it may offer new benefits or options for patients who do not respond well to current therapies. ^{6 7 8 9 10}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Current Drug Options for Raising HDL Cholesterol. [2020]

2. India pubmed.ncbi.nlm.nih.gov

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

3. United States pubmed.ncbi.nlm.nih.gov

New and emerging strategies for reducing cardiometabolic risk factors. [2017]

4. Poland pubmed.ncbi.nlm.nih.gov

[Pharmacologic treatment of lipid metabolism disorders]. [2010]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Medical lipid-regulating therapy: current evidence, ongoing trials and future developments. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Lipid-lowering therapy: Guidelines to precision medicine. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

A new statin: a new standard. [2023]

8. Ireland pubmed.ncbi.nlm.nih.gov

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

9. United States pubmed.ncbi.nlm.nih.gov

Update on dyslipidemia. [2007]

10. Spain pubmed.ncbi.nlm.nih.gov

Ezetimibe. [2022]