What side effects are associated with this type of intervention?

Common treatments for high cholesterol include statins, ezetimibe, and PCSK9 inhibitors. Statins can cause muscle pain, liver enzyme abnormalities, and rarely, rhabdomyolysis. Ezetimibe is generally well-tolerated but may cause gastrointestinal issues and, rarely, muscle pain. PCSK9 inhibitors, such as evolocumab and alirocumab, are associated with injection site reactions, mild allergic reactions, and rare neurocognitive symptoms. Serious adverse effects are uncommon for PCSK9 inhibitors.

What prior FDA approvals exist?

The FDA has approved several treatments for high cholesterol that are similar to MK-0616, an LDL-C lowering agent. Notably, PCSK9 inhibitors such as alirocumab and evolocumab have been approved for their ability to significantly reduce LDL-C levels by increasing the number of LDL receptors. Inclisiran, another PCSK9-targeting drug, has shown efficacy in clinical trials. Additionally, statins like atorvastatin and rosuvastatin, which lower LDL-C by inhibiting cholesterol synthesis in the liver, and ezetimibe, which reduces cholesterol absorption in the intestine, are also FDA-approved treatments for high cholesterol.

What other types of research exist?

Promising novel alternatives to MK-0616 for lowering LDL-C in high cholesterol patients include PCSK9 inhibitors such as evolocumab and alirocumab, which have shown significant efficacy in reducing LDL-C levels. Another emerging option is inclisiran, a small interfering RNA (siRNA) therapy that targets PCSK9 and has demonstrated durable LDL-C reduction in clinical trials. Mipomersen, an antisense oligonucleotide, is also a potential alternative, particularly for patients with homozygous familial hypercholesterolemia (HoFH). These therapies offer new avenues for patients who may not achieve their LDL-C goals with traditional statins or are intolerant to them.

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PCSK9 Inhibitor

Oral PCSK9 Inhibitor for High Cholesterol

Phase 3

Waitlist Available

Research Sponsored by Merck Sharp & Dohme LLC

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Is on a stable dose of all background lipid-lowering therapies (LLTs) with no planned medication change

Is treated with a moderate- or high-intensity statin medication

Must not have

Was previously treated/is being treated with certain other cholesterol lowering medications, including protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors

Has a history of homozygous familial hypercholesterolemia (FH) based on genetic or clinical criteria, compound heterozygous FH, or double heterozygous FH

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to ~60 weeks

Awards & highlights

Pivotal Trial

Summary

This trial is testing a new medication called MK-0616 to see if it can lower bad cholesterol levels in adults with a genetic condition that causes very high cholesterol. These patients often need special treatments because regular medications may not work well for them. The study will measure how much MK-0616 can reduce bad cholesterol over several months.

Who is the study for?

This trial is for adults with a condition called heterozygous familial hypercholesterolemia, which causes high cholesterol. Participants must have LDL-C levels above certain thresholds and be on stable doses of statins or other lipid-lowering therapies without plans to change them.

What is being tested?

The study tests MK-0616, an oral medication intended to lower 'bad' cholesterol (LDL-C), against a placebo. The main goal is to see if MK-0616 can significantly reduce LDL-C levels after 24 weeks compared to the placebo.

What are the potential side effects?

While specific side effects are not listed here, generally PCSK9 inhibitors like MK-0616 could cause symptoms such as nasal congestion, sneezing, sore throat, injection site reactions (if injectable), and back pain.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am on a consistent dose of my cholesterol medications with no changes expected.

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I am currently taking a strong cholesterol-lowering medication.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been treated with cholesterol-lowering drugs, including PCSK9 inhibitors.

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I have a genetic condition that causes very high cholesterol.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to ~60 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to ~60 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to ~60 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Mean percent change from baseline in low-density lipoprotein cholesterol (LDL-C) at Week 24

Number of participants who discontinue study drug due to an AE

Number of participants with one or more adverse events (AEs)

Secondary study objectives

Mean percent change from baseline in LDL-C at Week 52

Mean percent change from baseline in apolipoprotein B (ApoB) at Week 24

Mean percent change from baseline in non-high-density lipoprotein cholesterol (HDL-C) at Week 24

+3 more

Side effects data

From 2022 Phase 2 trial • 381 Patients • NCT05261126

Dyspepsia

Arthralgia

Fatigue

COVID-19

Nausea

Cholecystitis

Diarrhoea

Deep vein thrombosis

100%

80%

60%

40%

20%

Study treatment Arm

MK-0616 12 mg

MK-0616 18 mg

MK-0616 30 mg

Placebo

MK-0616 6 mg

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Enlicitide DecanoateExperimental Treatment1 Intervention

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

Group II: PlaceboPlacebo Group1 Intervention

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Enlicitide Decanoate

2024

Completed Phase 2

~450

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Statins work by inhibiting HMG-CoA reductase, an enzyme involved in cholesterol synthesis in the liver, leading to reduced LDL-C levels. Ezetimibe lowers cholesterol by inhibiting its absorption in the small intestine. PCSK9 inhibitors, such as the investigational drug MK-0616, increase the number of LDL receptors on liver cells by preventing PCSK9 from degrading these receptors, thereby enhancing the clearance of LDL-C from the bloodstream. These treatments are crucial for high cholesterol patients, especially those with familial hypercholesterolemia, as they significantly reduce the risk of cardiovascular events by effectively lowering LDL-C levels.