MK-2060 Safety Study in Healthy Participants

Recruiting at 1 trial location

Overseen By Toll Free Number

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Merck Sharp & Dohme LLC

Disqualifiers: Endocrine, Cardiovascular, Cancer, others

Compensation: Varies

Number of Visits: 1

Duration: 1 day

23 Participants Needed

Trial Summary

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

The trial protocol does not specify whether you need to stop taking your current medications.

What data supports the idea that MK-2060 Safety Study in Healthy Participants is an effective drug?

The available research does not provide any data on the effectiveness of MK-2060 as a treatment. The studies mentioned focus on other drugs and their effects, but none of them include information about MK-2060. Therefore, there is no evidence from the provided information to support the idea that MK-2060 is an effective treatment. ^{1 2 3 4 5}

What safety data is available for MK-2060?

The provided research does not contain any safety data specifically for MK-2060. The studies mentioned focus on other compounds such as MK-462, MK-571, and MK-801, none of which are identified as MK-2060 or its variants. Therefore, no relevant safety data for MK-2060 can be extracted from the given information. ^{1 2 3 4 6}

Is the drug MK-2060 a promising treatment in the MK-2060 Safety Study in Healthy Participants?

The drug MK-2060 shows promise because it has undergone extensive safety evaluations, including animal studies and early human trials, which help ensure its safety and effectiveness. These studies are designed to identify safe starting doses and monitor for any adverse effects, making the transition to human trials safer and more reliable. ^{7 8 9 10 11}

What is the purpose of this trial?

The goal of the study is to learn about the safety of MK-2060 and if people tolerate it when MK-2060 is given in different forms.

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for healthy individuals with a BMI between 18 and 32. Participants should be in good health before the study starts.

Inclusion Criteria

I am in good health overall.

My BMI is between 18 and 32.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of MK-2060 or placebo via intravenous infusion or syringe on Day 1

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with plasma samples collected at pre-specified time points

Up to 134 days

Treatment Details

Interventions

• MK-2060

Trial Overview The study aims to test the safety and tolerability of MK-2060, which may potentially treat blood clots and deep vein thrombosis. Some participants will receive MK-2060, while others will get a placebo for comparison.

Participant Groups

Group I: Panel E: MK-2060 IV (1 minute) Experimental Treatment 1 Intervention

Participants will receive a single dose of MK-2060 via syringe over 1 minute on Day 1.

Group II: Panel D: MK-2060 IV (2.5 minutes) Experimental Treatment 1 Intervention

Participants will receive a single dose of MK-2060 via syringe over 2.5 minutes on Day 1.

Group III: Panel C: MK-2060 IV (5 minutes) Experimental Treatment 1 Intervention

Participants will receive a single dose of MK-2060 via syringe over 5 minutes on Day 1.

Group IV: Panel B: MK-2060 IV (10 minutes) Experimental Treatment 1 Intervention

Participants will receive a single dose of MK-2060 via IV infusion over 10 minutes on Day 1.

Group V: Panel A: MK-2060 IV (20 minutes) Experimental Treatment 1 Intervention

Participants will receive a single dose of MK-2060 via intravenous (IV) infusion over 20 minutes on Day 1.

Group VI: Placebo Placebo Group 1 Intervention

Participants will receive a single dose of saline via IV infusion or syringe over MK-2060-matched time period on Day 1.

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

MK-8389 was found to be generally safe and well tolerated in healthy young women over a 14-day period, although it caused transient changes in thyroid function tests that limited dose escalation above 40 mg.

While MK-8389 showed acceptable systemic exposure, it did not have a clinically meaningful effect on follicular development, although higher doses did increase inhibin B levels, indicating some early follicular activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral follicle-stimulating hormone agonist tested in healthy young women of reproductive age failed to demonstrate effect on follicular development but affected thyroid function. Gerrits, MG., Kramer, H., el Galta, R., et al.[2016]

Intravenous doses of MK-462 ranging from 5 to 90 micrograms per kg were found to be well tolerated in healthy males, with linear pharmacokinetics observed for doses up to 60 micrograms per kg.

Food intake prior to oral administration of MK-462 increased its overall exposure (AUC) by about 20% but did not significantly affect peak concentration (Cmax) or half-life (t1/2), indicating that MK-462 can be taken with or without food without major impacts on its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and food interaction of MK-462 in healthy males. Cheng, H., Polvino, WJ., Sciberras, D., et al.[2012]

MK-801 significantly reduces brain lesion volume and cerebral edema in rat models of acute brain injury, based on a systematic review of 52 studies involving 2530 samples.

The treatment with MK-801 also improves neurological function and spatial cognition, indicating its potential as a neuroprotective agent with a favorable safety profile for future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MK-801 attenuates lesion expansion following acute brain injury in rats: a meta-analysis. Yi, NX., Zhou, LY., Wang, XY., et al.[2022]

MK-571, a leukotriene D4 receptor antagonist, was well tolerated in both intravenous and oral forms, with no serious side effects reported, even at high doses up to 1500 mg.

The study showed that MK-571 is rapidly absorbed when taken orally, with peak plasma concentrations reached within 1-2 hours, and a modest accumulation of the drug in plasma over multiple doses, indicating its potential for effective long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma drug profiles and tolerability of MK-571 (L-660,711), a leukotriene D4 receptor antagonist, in man. Depré, M., Margolskee, DJ., Hsieh, JY., et al.[2019]

In a study involving 20 Japanese patients with advanced colorectal cancer, the combination of MK-0646 with cetuximab and irinotecan was found to be well tolerated, with only one patient experiencing a dose-limiting toxicity (grade 3 hyperglycemia).

The combination therapy increased the exposure of MK-0646 by 25% without affecting the pharmacokinetics of cetuximab and irinotecan, although it did reduce the levels of SN-38, the active metabolite of irinotecan, indicating minimal drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 pharmacokinetic study of MK-0646 (dalotuzumab), an anti-insulin-like growth factor-1 receptor monoclonal antibody, in combination with cetuximab and irinotecan in Japanese patients with advanced colorectal cancer. Doi, T., Muro, K., Yoshino, T., et al.[2021]

In a study involving 12 healthy male volunteers, the pharmacokinetics of MK-571's enantiomers showed that their disposition is dose-dependent, with L-668,018 exhibiting a much more pronounced increase in exposure (AUC) compared to MK-0679 as the dose increased.

L-668,018 was eliminated from the body more quickly than MK-0679, suggesting that further investigation is needed to understand how L-668,018 may affect the disposition of MK-0679.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-dependent kinetics of the enantiomers of MK-571, and LTD4-receptor antagonist. Depré, M., Margolskee, DJ., Van Hecken, A., et al.[2019]

A comprehensive analysis of 45 case studies from 13 UK pharmaceutical companies suggests that animal toxicity studies longer than 6 months are generally unnecessary, except for specific carcinogenicity investigations.

The study emphasizes the potential to rationalize and improve the design of animal testing by utilizing existing toxicological data, which could lead to more efficient safety evaluations for new medicines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The value of chronic animal toxicology studies of pharmaceutical compounds: A retrospective analysis. Lumley, CE., Walker, SR.[2019]

A review of 58 drug candidates confirmed that nonclinical pharmacology and toxicology testing is crucial for determining safe starting doses in clinical trials, using metrics like No Observed Adverse Effect Levels (NOAELs) and Pharmacologically Active Doses (PADs).

The study found that starting doses for small molecules were conservatively set, often 10- to 100-fold lower than NOAELs, and the transition from nonclinical testing to Phase I trials has shown to be remarkably safe, with only a small percentage of studies exceeding NOAEL exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonclinical & clinical interface - extrapolation of nonclinical data to support Phase I clinical studies. Baldrick, P., Reichl, A.[2021]

High-Throughput Screening (HTS) of approximately 8,300 chemicals revealed evidence of non-monotonic dose-response (NMDR) relationships, which can complicate the assessment of chemical safety and efficacy, particularly for androgen receptor (AR) agonism.

The study identified NMDR in several compounds, including known AR antagonists and endocrine disruptors, highlighting the need for careful interpretation of HTS data to avoid misclassifying chemical activity based on traditional monotonic dose-response assumptions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Examining the evidence of non-monotonic dose-response in Androgen Receptor agonism high-throughput screening assay. Klimenko, K.[2021]

The recent fatal adverse event in the BIA-102474-101 clinical trial highlights significant limitations in the current safety review process for first-into-human trials, despite previous trials with similar compounds being conducted without incident.

To improve safety in future trials, it is crucial to implement sequential dosing strategies, thorough reviews of preclinical toxicity studies, and systematic risk assessments, especially for novel compounds that may pose higher risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implications of the BIA-102474-101 study for review of first-into-human clinical trials. Eddleston, M., Cohen, AF., Webb, DJ.[2021]

The European Medicines Agency (EMA) updated its 2007 guideline on First-in-Human (FIH) trials to enhance safety and efficacy assessments in early clinical development, particularly after the 2016 BIA 10-2474 incident.

The revised guideline emphasizes the importance of pharmacologic data in risk assessment and protocol design, aiming to provide clearer guidance for sponsors and ultimately improve subject safety in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Shared Learnings on the New EMA First-in-Human and Early Clinical Trial Guideline: Proceedings From a DIAlogue Session at DIA Europe 2018. van der Laan, JW., Benson, CT., Janssens, W., et al.[2021]

References

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

Oral follicle-stimulating hormone agonist tested in healthy young women of reproductive age failed to demonstrate effect on follicular development but affected thyroid function. [2016]

2. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and food interaction of MK-462 in healthy males. [2012]

3. India pubmed.ncbi.nlm.nih.gov

MK-801 attenuates lesion expansion following acute brain injury in rats: a meta-analysis. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Plasma drug profiles and tolerability of MK-571 (L-660,711), a leukotriene D4 receptor antagonist, in man. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

Phase 1 pharmacokinetic study of MK-0646 (dalotuzumab), an anti-insulin-like growth factor-1 receptor monoclonal antibody, in combination with cetuximab and irinotecan in Japanese patients with advanced colorectal cancer. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Dose-dependent kinetics of the enantiomers of MK-571, and LTD4-receptor antagonist. [2019]

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

The value of chronic animal toxicology studies of pharmaceutical compounds: A retrospective analysis. [2019]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Nonclinical & clinical interface - extrapolation of nonclinical data to support Phase I clinical studies. [2021]

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

Examining the evidence of non-monotonic dose-response in Androgen Receptor agonism high-throughput screening assay. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Implications of the BIA-102474-101 study for review of first-into-human clinical trials. [2021]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Shared Learnings on the New EMA First-in-Human and Early Clinical Trial Guideline: Proceedings From a DIAlogue Session at DIA Europe 2018. [2021]