MK-0616 for High Cholesterol
Recruiting in Palo Alto (17 mi)
+677 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
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)
Prior Safety Data
Trial Summary
What is the purpose of this trial?
This trial is testing MK-0616, a pill, in people with high cardiovascular risk. The goal is to see if it can prevent serious heart-related events by lowering bad cholesterol.
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.
What data supports the effectiveness of the drug MK-0616 for high cholesterol?
The research highlights the benefits of lowering LDL cholesterol (bad cholesterol) and raising HDL cholesterol (good cholesterol) to reduce the risk of heart disease. While specific data on MK-0616 is not provided, similar treatments like statins and fibrates have shown effectiveness in managing cholesterol levels and reducing cardiovascular events.12345
Eligibility Criteria
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.
I am over 18 and have had a major heart or blood vessel event.
See 2 more
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.
See 5 more
Trial Timeline
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
Treatment Details
Interventions
- MK-0616 (Monoclonal Antibodies)
Trial OverviewThe 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.
Participant Groups
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Enlicitide DecanoateExperimental Treatment1 Intervention
Participants receive enlicitide decanoate 20 mg once daily.
Group II: PlaceboPlacebo Group1 Intervention
Participants receive placebo once daily.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Brigham and Women's Hospital-Cardiovascular Medicine ( Site 0147)Boston, MA
Central Alabama Research ( Site 0109)Birmingham, AL
Trinity Health-Michigan d/b/a Michigan Heart ( Site 0186)Ypsilanti, MI
University of Minnesota, Lillehei Clinical Research Unit ( Site 0193)Minneapolis, MN
More Trial Locations
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Who Is Running the Clinical Trial?
Merck Sharp & Dohme LLCLead Sponsor
References
Current Drug Options for Raising HDL Cholesterol. [2020]Although circumstantial evidence supports raising high-density lipoprotein cholesterol (HDLC) in patients with low levels of HDLC, the scarcity of event-based trials has led to uncertainty with regard to the benefit of high-density lipoprotein (HDL)-raising therapy. Based on the National Cholesterol Education Program guidelines, therapy for dyslipidemia is focused initially on targeting low-density lipoprotein cholesterol (LDLC), and in patients with hypertriglyceridemia, secondarily on targeting non-HDLC. When HDLC remains low, the decision to target HDLC depends on the assessment of risk of cardiovascular events. We often consider drug therapy specifically to raise HDLC in high-risk patients, such as those with established atherosclerotic vascular disease, type 2 diabetes, or a Framingham risk score of 20% or above. The majority of high-risk patients require drug therapy, usually a statin, to achieve aggressive LDLC and non-HDLC goals, and thus many patients with low HDLC are candidates for statin therapy. However, a second drug is often required to achieve substantial HDL raising. Although no formal goals for HDLC exist, reasonable goals are HDLC greater than 40 mg/dL in men and greater than 50 mg/dL in women. We often add either niacin or a fibrate to a statin in high-risk patients with low HDLC levels. Targeting HDLC with pharmacologic therapy is a more difficult decision in moderate-risk patients, in whom therapy must be highly individualized.
FIELDS of dreams, fields of tears: a perspective on the fibrate trials. [2013]Endpoint studies have been performed with fibrates in coronary heart disease since 1971. The results have been confusing - starting with initial benefits in small studies, but contradicted by either minimal benefits in the Coronary Drug Project or adverse noncardiovascular (non-CV) effects in the World Health Organization Clofibrate Study. Fibrates returned for patients with low HDL-C and low LDL-C after a 25% event reduction were seen in the Veterans Affairs HDL Intervention Trial. The greater prominence ascribed to the lipid triad of the metabolic syndrome and the increasing prevalence of diabetes increased the topicality of fibrates given their main action of converting small dense to light buoyant LDL. The Fenofibrate Intervention in Event Lowering in Diabetes (FIELD) Study has carried on the tradition. Fenofibrate therapy in 9795 patients comprising a mixed low-risk primary and a medium-risk secondary prevention cohort resulted in an 11% reduction in coronary events (p = 0.16), a similar but significant reduction in CV events (p = 0.04; number needed to treat = 70). The benefits were concentrated in primary prevention and on nonfatal myocardial events, but the study was confounded by asymmetrical statin drop-in due to the LDL-C-lowering effect of fenofibrate. Safety was generally good, including in combination with statins, but old concerns about sudden death, pancreatitis and venous thrombosis returned. Unexpected benefits were seen with fenofibrate on microvascular endpoints including microalbuminuria and retinopathy. Fenofibrate is a reasonable second-line therapy for dyslipidaemia in diabetes and safe in combination therapy. Its benefits on microvascular disease and in combination therapy require further confirmation.
New and emerging strategies for reducing cardiometabolic risk factors. [2017]Several new drug therapies with beneficial effects on more than one of the cardiometabolic risk factors that contribute to the metabolic syndrome have been developed recently or are under investigation. Emerging risk factors for coronary heart disease (CHD), including low concentrations of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-1 (apoA-1), high levels of high-sensitivity C-reactive protein, and small dense low-density lipoprotein cholesterol particles, have been identified. We provide a detailed description of the mechanisms of action and findings from clinical trials of the new drug therapies and discuss established drug therapies with beneficial effects on emerging risk factors for CHD. The new and emerging drug therapies include an antiobesity agent that reduces atherogenic dyslipidemia and abnormal glucose metabolism; cholesteryl ester transfer protein inhibitors that increase HDL cholesterol and apoA-1 levels; glitazars that increase HDL cholesterol and decrease triglyceride concentrations, as well as improve abnormal glucose metabolism; and the amylin analog pramlintide and the incretin mimetic exenatide, both of which reduce body weight as well as improve abnormal glucose metabolism. The insulin-sensitizing effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs), which may help prevent new-onset diabetes mellitus, and the beneficial effects of the ARB telmisartan on the glucose and lipid profiles also are presented.
[Pharmacologic treatment of lipid metabolism disorders]. [2010]The aim of the treatment of dyslipidaemia is the primary and secondary prevention of coronary heart disease (CHD). Dietary therapy is the first line in the management of hyperlipidaemia. Lipid-lowering drugs should be used in patients with an inadequate dietary response, with CHD and/or multiple CHD risk factors. The choice of drug depends on the lipid disorder type, the desired plasma lipids reduction and presence of contraindications. Lipid-lowering drugs-anion-exchange resins, nicotinic acid and acipimox, fibrates, statins, probucol and two new classes used in experimental studies (ansamycins and ACAT inhibitors) are presented. Antiatherosclerotic properties of statins are characterized.
Medical lipid-regulating therapy: current evidence, ongoing trials and future developments. [2022]Coronary heart disease (CHD) is a major cause of morbidity and mortality worldwide. Elevated low density lipoprotein-cholesterol (LDL-C) and reduced high density lipoprotein-cholesterol (HDL-C) levels are well recognised CHD risk factors, with recent evidence supporting the benefits of intensive LDL-C reduction on CHD risk. Such observations suggest that the most recent National Cholesterol Education Program Adult Treatment Panel III guidelines, with LDL-C targets of 2.6 mmol/L, may result in under-treatment of a significant number of patients and form the basis for the proposed new joint European Societies treatment targets of 2 and 4 mmol/L, respectively, for LDL and total cholesterol. HMG-CoA reductase inhibitors (statins) reduce LDL-C by inhibiting the rate-limiting step in cholesterol biosynthesis and reduced CHD event rates in primary and secondary prevention trials. The magnitude of this effect is not fully accounted for by LDL-C reduction alone and may relate to effects on other lipid parameters such as HDL-C and apolipoproteins B and A-I, as well as additional anti-inflammatory effects. With increasing focus on the benefits of intensive cholesterol reduction new, more efficacious statins are being developed. Rosuvastatin is a potent, hydrophilic enantiomeric statin producing reductions in LDL-C of up to 55%, with about 80% of patients reaching European LDL-C treatment targets at the 10 mg/day dosage. The Heart Protection Study (HPS) demonstrated that LDL-C reduction to levels as low as 1.7 mmol/L was associated with significant clinical benefit in a wide range of high-risk individuals, including patients with type 2 diabetes mellitus, or peripheral and cerebrovascular disease, irrespective of baseline cholesterol levels, with no apparent lower threshold for LDL-C with respect to risk. Various large endpoint trials, including Treating to New Targets (TNT) and Study of Effectiveness of Additional reductions in Cholesterol and Homocysteine (SEARCH) will attempt to further address the issue of optimal LDL-C reduction. At low LDL-C levels, HDL-C becomes an increasingly important risk factor and is the primary lipid abnormality in over half of CHD patients, with the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study set to assess the effect of raising HDL-C on cardiovascular events in patients with low HDL-C and LDL-C levels below 3 mmol/L. A variety of agents are being developed, which affect both LDL-C and HDL-C metabolism, including inhibitors of acyl-coenzyme A-cholesterol acyl transferase, microsomal transfer protein and cholesterol ester transfer protein, as well as specific receptor agonists. Ezetimibe is a selective cholesterol absorption inhibitor, which produces reductions in LDL-C of up to 25 and 60% reduction in chylomicron cholesterol content with a 10 mg/day dosage. A 1 mmol/L reduction in LDL-C results in a 25% reduction in cardiovascular risk, independent of baseline LDL-C levels. Growing evidence supports the concept that lower is better for LDL-C and that increasing HDL-C represents an important therapeutic target. Furthermore, there is growing appreciation of the role of inflammation in atherogenesis. Consequently, increasing numbers of people should receive lipid-regulating therapy with the development of newer agents offering potential mechanisms of optimising lipid profiles and thus risk reduction. In addition, the pleiotropic anti-inflammatory effects of lipid lowering therapy may provide further risk reduction.