Enlicitide Decanoate for High Cholesterol

Recruiting at 35 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, Gout, 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: Unknown

Duration: 8 weeks

301 Participants Needed

Trial Summary

What is the purpose of this trial?

The main purpose of this study is to assess whether enlicitide decanoate is superior to ezetimibe or bempedoic acid or ezetimibe + bempedoic acid in reducing LDL-C in participants with hypercholesterolemia, and to evaluate its safety and tolerability. The primary study hypotheses are enlicitide decanoate is superior to ezetimibe, bempedoic acid, and ezetimibe + bempedoic acid on mean percent change from baseline in LDL-C at week 8.

Do I need to stop my current medications for this trial?

The trial requires you to stay on a stable dose of your current lipid-lowering therapies (LLTs) without any planned changes during the study. If you are taking certain cholesterol-lowering medications like ezetimibe, bempedoic acid, or PCSK9 inhibitors, you may need an adequate washout period before starting the trial.

What data supports the idea that Enlicitide Decanoate for High Cholesterol is an effective drug?

The available research shows that drugs targeting PCSK9, like Enlicitide Decanoate, are effective in lowering bad cholesterol levels, known as LDL-C. These drugs have been shown to improve heart health outcomes when used alongside other treatments. They are particularly useful for people who do not respond well to traditional cholesterol-lowering medications. Studies have demonstrated that PCSK9 inhibitors can significantly reduce the risk of heart attacks and strokes by lowering LDL-C levels. ^{1 2 3 4 5}

What safety data is available for Enlicitide Decanoate (MK-0616) for high cholesterol?

The safety data for PCSK9 inhibitors, which include Enlicitide Decanoate (MK-0616), indicates a generally favorable safety profile in clinical trials. However, real-world data shows some adverse events such as injection-site reactions, influenza-like illness, and myalgia. Neurocognitive adverse reactions and ocular disorders have also been reported, but the long-term safety remains unclear. Most adverse events resolve over time, and no specific patient subgroup at risk has been identified. ^{6 7 8 9 10}

Is the drug Enlicitide Decanoate a promising treatment for high cholesterol?

Yes, Enlicitide Decanoate, which is a type of PCSK9 inhibitor, is a promising treatment for high cholesterol. PCSK9 inhibitors are known to significantly lower bad cholesterol (LDL-C) levels and reduce the risk of heart attacks and strokes. They are especially useful for people who do not respond well to traditional cholesterol-lowering drugs. ^{2 3 4 11 12}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with high cholesterol who may have had a cardiovascular event or are at risk of one. They must be on a stable dose of statins, possibly with other lipid-lowering treatments, and meet specific LDL-C levels based on their heart disease history.

Inclusion Criteria

Has fasted lipid values at Visit 1 (Screening) meeting specific LDL-C criteria based on ASCVD history

I am on a stable dose of my current medications with no changes expected.

I am 18 years or older and can give informed consent.

Exclusion Criteria

I have a genetic condition that causes very high cholesterol.

I was treated with cholesterol medications recently without a break.

I am part of, or plan to join, an LDL cholesterol cleaning program.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either enlicitide decanoate or comparator drugs (ezetimibe, bempedoic acid, or both) for LDL-C reduction

8 weeks

Daily oral administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Enlicitide Decanoate

Trial Overview The study tests if Enlicitide Decanoate (an oral PCSK9 inhibitor) is better than Ezetimibe, Bempedoic Acid, or their combination in lowering 'bad' cholesterol (LDL-C). Participants will receive either the test drug or placebos to compare effects after 8 weeks.

Participant Groups

Group I: Enlicitide Decanoate Experimental Treatment 3 Interventions

Participants receive enlicitide decanoate 20mg, ezetimibe-matching placebo, and bempedoic acid-matching placebo once daily (QD) orally up to approximately 56 days.

Group II: Ezetimibe + Bempedoic Acid Active Control 3 Interventions

Participants receive ezetimibe 10 mg, bempedoic acid 180mg, enlicitide decanoate-matching placebo orally QD for approximately 56 days.

Group III: Ezetimibe Active Control 3 Interventions

Participants receive ezetimibe 10mg, enlicitide decanoate-matching placebo, and bempedoic acid-matching placebo QD orally up to approximately 56 days.

Group IV: Bempedoic Acid Active Control 3 Interventions

Participants receive bempedoic acid 180mg, ezetimibe-matching placebo, and enlicitide decanoate-matching placebo QD orally up to approximately 56 days.

Enlicitide Decanoate is already approved in United States for the following indications:

Approved in United States as Enlicitide Decanoate for:

• Hypercholesterolemia

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

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]

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 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]

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]

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]

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 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]

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]

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]

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]

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]

References

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

PCSK9 inhibition in clinical practice: Treatment patterns and attainment of lipid goals in a large health maintenance organization. [2021]

2. New Zealand 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. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Prevention of myocardial infarction and stroke with PCSK9 inhibitors treatment: a metanalysis of recent randomized clinical trials. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Proprotein convertase subtilisin/kexin type 9: a new target molecule for gene therapy. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Innovative, centralised, multidisciplinary medicines optimisation clinic for PCSK9 inhibitors. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Ocular disorders associated with PCSK9 inhibitors: A pharmacovigilance disproportionality analysis. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Proprotein convertase subtilisin/kexin type 9 inhibitors for reduction of cardiovascular events. [2021]

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

Increased Risk of Adverse Neurocognitive Outcomes With Proprotein Convertase Subtilisin-Kexin Type 9 Inhibitors. [2021]

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

Adverse Events Associated With PCSK9 Inhibitors: A Real-World Experience. [2021]

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

PCSK9 Inhibitors and Neurocognitive Adverse Drug Reactions: Analysis of Individual Case Safety Reports from the Eudravigilance Database. [2023]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Use of PCSK9 Inhibitors in Solid Organ Transplantation Recipients. [2021]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Trends in PCSK9 Inhibitor Prescriptions before and after the Price Reduction in Patients with Atherosclerotic Cardiovascular Disease. [2021]