Enlicitide Decanoate for High Cholesterol

Not currently recruiting at 281 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: PCSK9 inhibitors

Disqualifiers: Serious adverse event, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the safety and effectiveness of enlicitide decanoate for long-term treatment of high cholesterol. Enlicitide decanoate is a daily oral medication tested in individuals who have completed earlier studies with similar treatments. Eligible participants must have finished a previous enlicitide decanoate study and adhered to the study protocols. The trial excludes anyone who discontinued earlier treatment due to serious side effects. As a Phase 3 trial, this study represents the final step before FDA approval, allowing participants to contribute to a potentially groundbreaking treatment.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot start treatment with a nonstudy PCSK9 inhibitor while enrolled.

Is there any evidence suggesting that enlicitide decanoate is likely to be safe for humans?

Research has shown that enlicitide decanoate is generally safe for people. In earlier studies, patients taking this treatment experienced significant reductions in their LDL cholesterol, often referred to as "bad" cholesterol. Importantly, these studies consistently found the treatment to be as safe as a placebo, with no major safety issues reported.

This trial is a Phase 3 study, indicating that the treatment has already passed initial safety tests in earlier phases. Phase 3 trials typically involve more participants to further confirm safety and effectiveness. This means enlicitide decanoate was deemed safe in earlier studies, and researchers are now evaluating its safety for long-term use. ^{1 2 3 4 5}

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

Enlicitide Decanoate is unique because it offers a novel approach to treating high cholesterol by using a new active ingredient. Unlike traditional statins or PCSK9 inhibitors, which are common in current cholesterol management, Enlicitide Decanoate works by a different mechanism, potentially offering an alternative for those who don't respond well to existing treatments. Researchers are excited about this treatment because it is administered orally once daily, which could improve patient adherence compared to some injectable options. This innovative approach might provide a new avenue for managing high cholesterol effectively.

What evidence suggests that enlicitide decanoate might be an effective treatment for high cholesterol?

Studies have shown that enlicitide decanoate effectively lowers LDL cholesterol, often referred to as "bad" cholesterol. Specifically, this treatment led to a significant and noticeable drop in LDL cholesterol levels in adults with high cholesterol. Research indicates that enlicitide decanoate can reduce LDL cholesterol levels by more than 50%, making it one of the most effective options for lowering cholesterol currently under study. The treatment is also considered safe, with side effects similar to those of a placebo. These results suggest that enlicitide decanoate could be a strong option for managing high cholesterol. ^{1 2 3 5 6}

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 with high cholesterol who have already completed one of the earlier enlicitide decanoate studies (MK-0616-013, MK-0616-017, or MK-0616-018). Specific eligibility details are not provided but typically include meeting certain health standards and previous study participation.

Inclusion Criteria

Has completed an enlicitide decanoate parent study per protocol (including the final assessments/procedures of their parent study)

Had an overall study intervention compliance ≥80% while participating in their parent study

Exclusion Criteria

Has discontinued study intervention in their parent study

Is currently participating in an interventional clinical study other than an enlicitide decanoate parent study

I am experiencing a serious side effect from a previous study treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 20 mg of enlicitide decanoate orally once daily

8 weeks

Weekly visits (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Open-label extension

Participants continue to receive enlicitide decanoate to evaluate long-term safety and efficacy

Up to approximately 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Enlicitide Decanoate

Trial Overview The trial is testing the long-term safety and effectiveness of a drug called Enlicitide Decanoate in managing high cholesterol. This extension study follows up on participants from prior related trials to gather more data over a longer period.

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)

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

In a real-world analysis of 164 patients, 41.5% reported adverse events (AEs) after using PCSK9 inhibitors, with the most common being injection-site reactions (33.8%) and influenza-like illness (27.9%).

The overall safety profile of PCSK9 inhibitors in clinical practice is comparable to that observed in randomized clinical trials, indicating they are well tolerated, with AEs resolving in 71.1% of cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events Associated With PCSK9 Inhibitors: A Real-World Experience. Gürgöze, MT., Muller-Hansma, AHG., Schreuder, MM., et al.[2021]

In a review of 2041 Individual Case Safety Reports, 22.7% reported neuropsychiatric adverse drug reactions (ADRs) associated with PCSK9 inhibitors alirocumab and evolocumab, with common issues including headache, insomnia, and depression.

Both alirocumab and evolocumab showed a higher likelihood of reporting neurological ADRs compared to statins, indicating a potential safety concern that warrants further investigation in real-life settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PCSK9 Inhibitors and Neurocognitive Adverse Drug Reactions: Analysis of Individual Case Safety Reports from the Eudravigilance Database. di Mauro, G., Zinzi, A., Scavone, C., et al.[2023]

After a significant price reduction in March 2018, the prescription rate of PCSK9 inhibitors for eligible patients with atherosclerotic cardiovascular disease (ASCVD) increased from 0.5% to 3.3%, indicating improved access to this effective treatment.

While adherence to PCSK9 inhibitors improved, particularly among younger patients with commercial insurance, older patients and those on Medicare still face barriers to access, suggesting that further price reductions and studies on prescribing barriers are necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trends in PCSK9 Inhibitor Prescriptions before and after the Price Reduction in Patients with Atherosclerotic Cardiovascular Disease. Smith, A., Johnson, D., Banks, J., et al.[2021]

A large analysis of over 103,000 reports found that PCSK9 inhibitors are associated with increased occurrences of ocular adverse events, particularly increased lacrimation, seasonal allergies, and eye operations, especially in women and individuals over 65 years old.

The study suggests that these ocular adverse events typically occur within 30 days of starting treatment, highlighting the need for monitoring in at-risk populations when prescribing PCSK9 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocular disorders associated with PCSK9 inhibitors: A pharmacovigilance disproportionality analysis. Zhao, X., Wu, J., Zhu, S.[2023]

PCSK9 is a promising target for lowering LDL cholesterol levels and reducing cardiovascular disease risk, especially since current lipid-lowering medications often increase PCSK9 levels and do not adequately protect all patients from cardiovascular events.

The review discusses various therapeutic strategies under investigation, including antibodies, antisense oligonucleotides, and small interfering RNAs (siRNAs), which aim to inhibit PCSK9 expression and activity, offering new hope for treating hypercholesterolemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proprotein convertase subtilisin/kexin type 9: a new target molecule for gene therapy. Banaszewska, A., Piechota, M., Plewa, R.[2021]

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are a promising new class of lipid-lowering therapies that can effectively manage high cholesterol levels in patients who have undergone solid organ transplantation.

PCSK9i are considered a safe option for these patients, addressing the challenges posed by traditional lipid-lowering therapies that may interact negatively with immunosuppressant medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of PCSK9 Inhibitors in Solid Organ Transplantation Recipients. Warden, BA., Kaufman, T., Minnier, J., et al.[2021]

In a study of 1600 patients using PCSK9 inhibitors (PCSK9i) for cholesterol management, nearly half (49.9%) discontinued treatment after 3 years, highlighting a significant challenge in long-term adherence.

Despite the high discontinuation rates, 58% of those who stopped therapy eventually re-initiated treatment, but overall adherence was low, with only 29% maintaining a high level of medication coverage (≥80%), which correlated with lower success in achieving LDL cholesterol targets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PCSK9 inhibition in clinical practice: Treatment patterns and attainment of lipid goals in a large health maintenance organization. Zafrir, B., Egbaria, A., Stein, N., et al.[2021]

PCSK9 inhibitors do not show an increased risk of serious adverse events, musculoskeletal issues, or stroke, based on a meta-analysis of 11 studies involving both early-phase and larger outcome trials.

However, there is a potential signal for increased neurocognitive adverse events in larger studies, suggesting the need for careful monitoring of these effects in ongoing research and post-marketing surveillance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased Risk of Adverse Neurocognitive Outcomes With Proprotein Convertase Subtilisin-Kexin Type 9 Inhibitors. Khan, AR., Bavishi, C., Riaz, H., et al.[2021]

PCSK9 inhibitors significantly reduce the incidence of myocardial infarction by 19% and stroke by 25%, based on a meta-analysis of 81,700 patients, with 41,979 receiving the treatment.

The treatment did not show any effect on mortality rates, indicating that while PCSK9 inhibitors are effective in reducing certain cardiovascular events, they do not impact overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of myocardial infarction and stroke with PCSK9 inhibitors treatment: a metanalysis of recent randomized clinical trials. Cordero, A., Rodríguez-Mañero, M., Fácila, L., et al.[2022]

In a study of 98 older adults prescribed PCSK9 inhibitors, LDL cholesterol levels were significantly reduced by an average of 60% within 6 months, demonstrating the efficacy of this treatment in lowering cholesterol levels.

While PCSK9 inhibitors were generally well-tolerated, with few side effects reported, the high out-of-pocket expenses (OPE) posed a significant barrier to therapy initiation for many patients, highlighting the need for better cost management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Retrospective Chart Review Evaluating Efficacy, Tolerability, and Cost of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9i) in Older Adults. Davis, LE., Pogge, EK.[2021]

PCSK9 inhibitors, like alirocumab and evolocumab, effectively lower LDL cholesterol levels by 55-60% and have been shown to reduce cardiovascular events, similar to the effects of statins, based on large clinical trials.

These medications are generally safe with minimal side effects, but their high cost (around $14,000 annually in the U.S.) limits their routine use, suggesting that careful patient selection is necessary to maximize their benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proprotein convertase subtilisin/kexin type 9 inhibitors for reduction of cardiovascular events. Turgeon, RD., Pearson, GJ.[2021]

A new centralized multidisciplinary clinic successfully initiated PCSK9 inhibitor therapy for 48 out of 100 referred patients, leading to significant reductions in cholesterol levels: total cholesterol decreased by 41% and LDL-C by 58% after 3 months.

The positive outcomes were maintained over 12 months, with LDL-C reductions of 65% and high patient satisfaction, indicating that this model could enhance access and adherence to PCSK9i therapy in other regions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovative, centralised, multidisciplinary medicines optimisation clinic for PCSK9 inhibitors. Khatib, R., Khan, M., Barrowcliff, A., et al.[2022]

Citations

1. 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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05952856

NCT05952856 | A Study of Enlicitide Decanoate (MK-0616 ... The goal of this study is to evaluate the efficacy, safety, and tolerability of enlicitide decanoate in adult participants with hypercholesterolemia.

3. thecardiologyadvisor.com thecardiologyadvisor.com/news/oral-pcsk9-inhibitor-enlicitide-reduces-ldl-c-in-adults-with-hypercholesterolemia/

Oral PCSK9 Inhibitor Enlicitide Reduces LDL-C in Adults ... Findings showed treatment with enlicitide resulted in a statistically significant and clinically meaningful reduction in LDL-C, as well as in ...

4. appliedclinicaltrialsonline.com appliedclinicaltrialsonline.com/view/merck-oral-pcsk9-inhibitor-demonstrates-efficacy-hypercholesterolemia

Merck's Oral PCSK9 Inhibitor Demonstrates Efficacy in ... Favorable Safety Profile: Enlicitide demonstrated comparable adverse events to placebo and low discontinuation rates, reinforcing its potential ...

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

Emerging oral therapeutic strategies for inhibiting PCSK9 In terms of efficacy, enlicitide decanoate showed the strongest lipid lowering property exceeding the 50 % reduction of LDL cholesterol, target ...

6. healio.com healio.com/news/cardiology/20250613/topline-data-show-efficacy-safety-of-novel-oral-pcsk9-inhibitor-for-ldl-lowering

Topline data show efficacy, safety of novel oral PCSK9 ... Enlicitide decanoate demonstrated meaningful LDL lowering in patients with heterozygous familial hypercholesterolemia and those with hyperlipidemia vs. placebo.