A Study to Evaluate the Safety, Tolerability, and Drug Levels of MYK-224 Administered in Single and Multiple Doses in Healthy Adult Japanese Participants

Recruiting at 1 trial location

Overseen By First line of email MUST contain NCT # and Site #.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Bristol-Myers Squibb

Disqualifiers: Heart disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4-8 weeks

36 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial is for healthy participants without any acute or chronic medical illnesses, so it seems likely that you should not be on any current medications. However, the protocol does not specify this explicitly.

What evidence supports the effectiveness of the drug MYK-224?

Research shows that targeting the MYC protein, which is involved in many cancers, can halt tumor growth. Although MYK-224 is not directly mentioned, similar strategies to inhibit MYC have shown promise in reducing cancer cell proliferation. ^{1 2 3 4 5}

Is the treatment MYK-224 generally safe for humans?

Kinase inhibitors, like MYK-224, can cause heart-related side effects such as irregular heartbeats and high blood pressure. These effects are common with this type of drug, so it's important to monitor heart health during treatment. ^{6 7 8 9 10}

How does the drug MYK-224 differ from other treatments for cancer?

MYK-224 is unique because it targets the Myc protein, which plays a crucial role in cancer cell growth. Unlike other treatments, it aims to inhibit Myc's function, potentially stopping tumor growth and offering a new approach for cancers driven by Myc overexpression. ^{1 3 5 11 12}

What is the purpose of this trial?

This trial is testing a new drug called MYK-224 in healthy adult Japanese participants to see how different doses affect them.

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

Inclusion Criteria

Healthy as determined by medical history, physical examination, vital signs,12-lead electrocardiogram and routine laboratory assessments

Must have documented left Ventricular Ejection Fraction (LVEF) ≥60% (2D biplane Simpson's Method) at screening as determined by the echocardiographic core laboratory.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive single and multiple doses of MYK-224 to evaluate safety, tolerability, and pharmacokinetics

4-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• MYK-224
• Placebo

Participant Groups

Group I: Arm 4 Experimental Treatment 2 Interventions

Group II: Arm 3 Experimental Treatment 2 Interventions

Group III: Arm 2 Experimental Treatment 2 Interventions

Group IV: Arm 1 Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

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]

A machine-learning model was developed using data from 4638 patients across 16 FDA-approved small molecule kinase inhibitors (SMKIs) to analyze the relationship between kinase targets and adverse events (AEs), providing a new tool for predicting safety risks in cancer treatments.

The model not only helps identify potential kinase-inhibitor adverse event pairs but also serves as a precision medicine tool to enhance patient safety by forecasting clinical safety signals and aiding in the development of safer SMKI therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decoding kinase-adverse event associations for small molecule kinase inhibitors. Gong, X., Hu, M., Liu, J., et al.[2022]

References

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

Targeting Translation Initiation Bypasses Signaling Crosstalk Mechanisms That Maintain High MYC Levels in Colorectal Cancer. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Strategies to target the cancer driver MYC in tumor cells. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Cancer therapeutics: targeting the dark side of Myc. [2022]

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

Therapeutic strategies to inhibit MYC. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

MYC-mediated synthetic lethality for treating tumors. [2019]

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

Off-target pharmacological activity at various kinases: Potential functional and pathological side effects. [2023]

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

Cardiovascular Toxicity Induced by Kinase Inhibitors: Mechanisms and Preclinical Approaches. [2021]

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

Deconvoluting Kinase Inhibitor Induced Cardiotoxicity. [2018]

9. 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]

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

Decoding kinase-adverse event associations for small molecule kinase inhibitors. [2022]

11. China pubmed.ncbi.nlm.nih.gov

The effects of recombinant RA538 and antisense c-myc adenovirus on tumor cells and the molecular mechanism concerned. [2012]

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

Myc and mTOR converge on a common node in protein synthesis control that confers synthetic lethality in Myc-driven cancers. [2022]