Drug Interaction Study with Healthy Subjects

Overseen By Toll Free Number

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Cannabis, Herbal remedies

Disqualifiers: Seizures, Cancer, Depression, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how the body processes a new medicine, bomedemstat (an LSD1 inhibitor), which might help treat rare blood diseases. Researchers aim to observe bomedemstat's behavior when taken alone and its interaction with another medicine, carbamazepine. Participants will initially take bomedemstat, then later combine it with carbamazepine to observe any changes. The trial seeks healthy, non-smoking individuals with no recent use of nicotine or cannabis products. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

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.

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

Studies have shown that bomedemstat is generally well-tolerated by patients. One study found that many participants safely continued using the treatment and experienced benefits. Other research has found that bomedemstat led to positive blood responses in most patients with certain conditions. Early findings suggest that when bomedemstat is combined with another medicine, it remains well-tolerated and helps improve some symptoms.

In this trial, researchers are studying how bomedemstat interacts with carbamazepine, another medicine. Although specific safety data for this combination is not yet available, previous studies of bomedemstat alone show promising results. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Bomedemstat is unique because it targets the LSD1 enzyme, which plays a role in regulating blood cell production. Unlike traditional treatments that may not focus on this specific mechanism, Bomedemstat offers a novel approach by potentially modifying the underlying disease process rather than just alleviating symptoms. Researchers are excited about Bomedemstat because it could offer improved efficacy and safety for patients by addressing the root cause of certain blood disorders, providing a new pathway for treatment that current options don't address.

What evidence suggests that bomedemstat might be an effective treatment for rare blood diseases?

Studies have shown that bomedemstat can help treat certain blood diseases. Research indicates that it normalizes platelet counts, crucial for blood clotting, in all patients studied. It also reduces high white blood cell counts, which can be problematic in these conditions. Early findings suggest that bomedemstat improves symptoms like an enlarged spleen when combined with other treatments. While most studies focus on its safety and effects, early evidence is promising for its use in blood diseases. In this trial, participants will receive a single dose of bomedemstat, followed by a combination with carbamazepine to study potential drug interactions. ^{6 7 8 9 10}

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 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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment Period 1

A single dose of bomedemstat is administered on Day 1

1 day

1 visit (in-person)

Washout

A 7-day washout period between bomedemstat dosing in Period 1 and the first carbamazepine dose in Period 2

1 week

Treatment Period 2

Carbamazepine is administered twice daily for 17 days, with a single dose of bomedemstat on Day 14

17 days

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bomedemstat

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

LSD1 is overexpressed in many human tumors, making it a target for cancer treatment, and a new docking protocol was developed to identify potential inhibitors quickly.

The compound L05 was found to be a potent and selective inhibitor of LSD1, effectively reducing colorectal cell migration without causing significant harm to healthy cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of selective and reversible LSD1 inhibitors with anti-metastasis activity by high-throughput docking. Li, L., Li, R., Wang, Y.[2020]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06351631

NCT06351631 | A Study to Evaluate Safety and Efficacy of ... The study will include participants who are safely tolerating bomedemstat, receiving clinical benefit from its use in estimation of the investigator, and have ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-01821

A Study of Bomedemstat (IMG-7289/MK-3543) Compared ... This is a study evaluating the safety and efficacy of bomedemstat (MK-3543) compared with the best available therapy (BAT) in participants with essential ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9431221/

P1051: A PHASE 2 STUDY OF IMG-7289 (BOMEDEMSTAT ... The most common non-hematologic AEs reported by patients was dysgeusia in 36% (32/90) and diarrhoea in 34% (31/90). All dysgeusia events were ...

4. veri.larvol.com veri.larvol.com/news/bomedemstat-img-7289/drug

News - bomedemstat (MK-3543) Conclusions These early results suggest that the addition of bomedemstat to a ruxolitinib regimen is well tolerated, improves splenomegaly and symptom scores, ...

5. researchgate.net researchgate.net/publication/365826739_A_Phase_2_Study_of_the_LSD1_Inhibitor_Bomedemstat_IMG-7289_for_the_Treatment_of_Essential_Thrombocythemia_ET

A Phase 2 Study of the LSD1 Inhibitor Bomedemstat (IMG- ... In terms of efficacy, bomedemstat normalized platelet counts in 100% of the patients evaluated, decreased leucocytosis without inducing ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06351631

NCT06351631 | A Study to Evaluate Safety and Efficacy of ... The study will include participants who are safely tolerating bomedemstat, receiving clinical benefit from its use in estimation of the investigator, and have ...

7. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/747/502285/Bomedemstat-IMG-7289-an-LSD1-Inhibitor-Manages-the

Bomedemstat (IMG-7289), an LSD1 Inhibitor, Manages the ... This study demonstrates that treatment with bomedemstat results in a consistent hematologic response in the majority of patients with ET.

8. msdclinicaltrials.com msdclinicaltrials.com/trial/nct06079879/

A Study of Bomedemstat Compared to Best Available Therapy ... The primary study hypothesis is that bomedemstat is superior to the best available therapy with respect to durable clinicohematologic response (DCHR).

9. merck.com merck.com/news/merck-announces-phase-3-trial-initiation-for-bomedemstat-an-investigational-candidate-for-the-treatment-of-certain-patients-with-essential-thrombocythemia/

Merck Announces Phase 3 Trial Initiation for Bomedemstat, ... Bomedemstat (MK-3543) is an investigational small molecule, irreversible LSD1 inhibitor being developed by Merck. LSD1 regulates the ...

10. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123052254

Phase 2 Study to Assess the Safety and Efficacy of ... These early results suggest that the addition of bomedemstat to a ruxolitinib regimen is well tolerated, improves splenomegaly and symptom scores, and ...