Drug Interaction Study with Healthy Subjects

Recruiting in Palo Alto (17 mi)

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Merck Sharp & Dohme LLC

No Placebo Group

Trial Summary

What is the purpose of this trial?

Researchers have designed a study medicine called bomedemstat (MK-3543) as a new way to treat certain rare blood diseases. The purpose of this study is to learn what happens to bomedemstat in a person's body over time (a pharmacokinetic or PK study). Researchers will compare what happens to bomedemstat in the body when it is given alone and after multiple doses of another medicine called carbamazepine (CBZ).

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

Yes, you must stop taking all drugs, including prescription and non-prescription medications, herbal remedies, or vitamin supplements, starting 14 days before entering the study.

What data supports the idea that the drug is an effective treatment?

The available research shows that Bomedemstat (IMG-7289) is being studied as a potential treatment for various cancers. It is part of a group of drugs called LSD1 inhibitors, which are being tested for their ability to treat different types of cancer, including blood cancers and solid tumors. Although the research highlights that another drug, iadademstat, is the most potent among similar drugs, Bomedemstat is still considered a promising candidate and has entered clinical trials. This suggests that it has shown some effectiveness in early studies, but more research is needed to fully understand its potential. ^{1 2 3 4 5}

What safety data is available for Bomedemstat and related treatments?

Bomedemstat (IMG-7289) is a lysine-specific demethylase 1 (LSD1) inhibitor that has been evaluated in clinical trials for its potential as an anticancer treatment. The study titled 'Comprehensive in Vitro Characterization of the LSD1 Small Molecule Inhibitor Class in Oncology' mentions that Bomedemstat is among the new chemical entities that have reached clinical trials in oncology. However, the study does not provide specific safety data for Bomedemstat. The research primarily focuses on the characterization of LSD1 inhibitors, including Bomedemstat, in terms of their potency and selectivity as potential anticancer treatments. Therefore, while Bomedemstat has been studied in clinical trials, specific safety data from these trials is not detailed in the provided research. ^{2 3 4 6 7}

Is the drug Bomedemstat a promising treatment?

Bomedemstat is a promising drug because it targets LSD1, an enzyme linked to cancer growth. It has shown potential in treating various cancers by disrupting cancer cell processes and promoting cell differentiation. Bomedemstat is one of several LSD1 inhibitors that have reached clinical trials, indicating its potential as an effective cancer treatment. ^{2 3 5 6 8}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for healthy adults with no significant medical history, who haven't smoked or used nicotine products in the last 3 months. Participants should have a BMI between 18.0 and 32.0 kg/m2.

Inclusion Criteria

My BMI is between 18.0 and 32.0.

I am generally healthy with no major medical issues.

I have not smoked or used nicotine products for at least 3 months.

Treatment Details

Interventions

• Bomedemstat (Epigenetic Modulator)

Trial Overview The study is testing bomedemstat, a new potential treatment for rare blood diseases, to see how it behaves in the body over time alone and when taken with carbamazepine, another medication.

Participant Groups

Group I: Bomedemstat + Carbamazepine Experimental Treatment 2 Interventions

A single dose of bomedemstat will be administered On Day 1 of Period 1. There will be a washout of 7 days between bomedemstat dosing in Period 1 and the first carbamazepine (CBZ) dose in Period 2. In Period 2, CBZ will be administered twice daily (BID) for 17 consecutive days, with a single dose of bomedemstat coadministered with the morning dose on Day 14.

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

Lysine-specific demethylase 1 (LSD1) is crucial for regulating cell differentiation and proliferation, and various inhibitors have been developed to target its activity in cancer treatment.

Among the LSD1 inhibitors studied, iadademstat (ORY-1001) was found to be the most potent, while many commonly used tool compounds showed low activity and selectivity, indicating that results from these compounds should be interpreted cautiously.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive in Vitro Characterization of the LSD1 Small Molecule Inhibitor Class in Oncology. Sacilotto, N., Dessanti, P., Lufino, MMP., et al.[2022]

In castrate resistant prostate cancer (CRPC) models driven by the AR-V7 variant, inhibiting the enzyme LSD1 significantly reduced activation of both the wild type and AR-V7 forms of the androgen receptor.

This study suggests that targeting LSD1 could be a promising therapeutic strategy for treating CRPC, as it plays a role in the activation of androgen receptors that contribute to cancer progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LSD1 inhibition attenuates androgen receptor V7 splice variant activation in castration resistant prostate cancer models. Regufe da Mota, S., Bailey, S., Strivens, RA., et al.[2022]

Iadademstat, a selective LSD1 inhibitor, was found to be safe and well-tolerated in a phase I trial involving 27 patients with relapsed/refractory acute myeloid leukemia (R/R AML), with a recommended dose of 140 µg/m2/d established for further treatment.

The treatment showed promising signs of efficacy, including reductions in blood and bone marrow blast percentages and one complete remission, particularly in patients with MLL/KMT2A-rearranged AML, indicating its potential as a therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Phase I Study of Iadademstat (ORY-1001): A First-in-Class Lysine-Specific Histone Demethylase 1A Inhibitor, in Relapsed or Refractory Acute Myeloid Leukemia. Salamero, O., Montesinos, P., Willekens, C., et al.[2021]

Nine LSD1 inhibitors have progressed to clinical trials for treating hematologic malignancies, showing promise as either standalone or combination therapies.

Innovative design strategies, such as the unique binding mode of quinazoline derivatives, are paving the way for the development of reversible LSD1 inhibitors, which may help minimize side effects in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances of LSD1/KDM1A inhibitors for disease therapy. Zhang, C., Wang, Z., Shi, Y., et al.[2023]

A new series of derivatives of the LSD1 inhibitor S2157 were developed to improve safety and efficacy, particularly by reducing hERG channel inhibition and enhancing microsomal stability.

The most promising derivative, S1427, demonstrated strong LSD1 inhibitory activity while maintaining favorable safety profiles, making it a potential candidate for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design and Synthesis of Tranylcypromine-Derived LSD1 Inhibitors with Improved hERG and Microsomal Stability Profiles. Koda, Y., Sato, S., Yamamoto, H., et al.[2023]

A new rapid cell-based assay using CD86 as a biomarker can effectively indicate the inhibition of the LSD1 enzyme in human acute myeloid leukemia THP1 cells, providing a sensitive method for screening potential LSD1 inhibitors.

The study demonstrated that within 24 hours of treatment with a low nanomolar LSD1 inhibitor, CD86 expression significantly increased in a dose-dependent manner, confirming its potential as a reliable indicator of LSD1 activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD86 expression as a surrogate cellular biomarker for pharmacological inhibition of the histone demethylase lysine-specific demethylase 1. Lynch, JT., Cockerill, MJ., Hitchin, JR., et al.[2017]

Tranylcypromine (TCP) derivatives have been identified as potent inhibitors of the cancer-related enzyme LSD1, with compounds 18b and 19b showing over 10,000-fold selectivity against monoamine oxidases MAO-A and MAO-B, indicating their potential as targeted cancer therapies.

These LSD1 inhibitors were effective in activating CD86 expression in human AML cells after 10 days, suggesting they not only inhibit LSD1 but also exhibit cytotoxic effects on cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tying up tranylcypromine: Novel selective histone lysine specific demethylase 1 (LSD1) inhibitors. Ji, YY., Lin, SD., Wang, YJ., et al.[2017]

References

1. England pubmed.ncbi.nlm.nih.gov

Identification of selective and reversible LSD1 inhibitors with anti-metastasis activity by high-throughput docking. [2020]

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

Comprehensive in Vitro Characterization of the LSD1 Small Molecule Inhibitor Class in Oncology. [2022]

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

LSD1 inhibition attenuates androgen receptor V7 splice variant activation in castration resistant prostate cancer models. [2022]

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

First-in-Human Phase I Study of Iadademstat (ORY-1001): A First-in-Class Lysine-Specific Histone Demethylase 1A Inhibitor, in Relapsed or Refractory Acute Myeloid Leukemia. [2021]

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

Recent advances of LSD1/KDM1A inhibitors for disease therapy. [2023]

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

Design and Synthesis of Tranylcypromine-Derived LSD1 Inhibitors with Improved hERG and Microsomal Stability Profiles. [2023]

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

CD86 expression as a surrogate cellular biomarker for pharmacological inhibition of the histone demethylase lysine-specific demethylase 1. [2017]

8. France pubmed.ncbi.nlm.nih.gov

Tying up tranylcypromine: Novel selective histone lysine specific demethylase 1 (LSD1) inhibitors. [2017]