EDG-7500 for Healthy Subjects

Overseen By Edgewise Therapeutics, Inc.

Age: 18 - 65

Sex: Male

Trial Phase: Phase 1

Sponsor: Edgewise Therapeutics, Inc.

Disqualifiers: Alcohol or drug abuse, Radiation exposure, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called [14C]-EDG-7500, an experimental drug, to determine how the body processes and eliminates it. Researchers aim to understand how this drug moves through the blood and is expelled in urine and feces after a single dose. The trial is open to healthy men who do not smoke and have no recent history of serious health issues or substance abuse. Participants should maintain a stable daily routine for bathroom habits and have no recent exposure to significant radiation or participation in similar studies. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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

The protocol does not specify whether you need to stop taking your current medications. However, since the trial is for healthy subjects, it's likely that participants should not be on any medications that could affect the study results. Please consult with the trial coordinators for specific guidance.

Is there any evidence suggesting that EDG-7500 is likely to be safe for humans?

Research shows that EDG-7500, a new treatment, has been tested in both healthy individuals and patients with obstructive hypertrophic cardiomyopathy (HCM). In these studies, EDG-7500 appeared safe. Healthy participants generally tolerated the treatment well, with no major safety issues reported. This suggests potential safety for EDG-7500, but it is important to note that this early research focuses on understanding how the drug moves through and exits the body. Further studies are necessary to confirm these findings and ensure the treatment's long-term safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about EDG-7500 because it represents a novel approach in its class. Unlike standard treatments that often target symptoms, EDG-7500 is being studied for its unique interaction with metabolic pathways, thanks to its [14C] labeling. This feature allows for precise tracking and understanding of the drug's absorption, distribution, metabolism, and excretion in the human body. Such insights could lead to more tailored and effective treatments in the future.

What evidence suggests that EDG-7500 could be effective?

Research has shown that EDG-7500 could be a promising treatment for heart conditions. One study found it reduced a key heart failure marker, NT-proBNP, by 62%. This suggests it might help manage heart issues like hypertrophic cardiomyopathy, where the heart muscle thickens. EDG-7500 specifically targets heart muscle function. Early trials in healthy individuals found it was well-tolerated and did not affect the heart's ability to pump. These results highlight its potential benefits for heart-related conditions. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for healthy adult men who can participate in a study to understand how a new drug, [14C]-EDG-7500, behaves in the body after being taken orally. Specific eligibility criteria are not provided.

Inclusion Criteria

BMI ≥ 18.0 kg/m2 and ≤ 32.0 kg/m2 at Screening; body weight ≥ 55.0 kg and ≤ 100.0 kg at Screening

Non-smoker

I am a man aged between 18 and 55 years old.

Exclusion Criteria

I haven't had any radiation exposure, except for dental or basic X-rays, in the last year.

Glomerular filtration rate (GFR) < 80 mL/min/1.73 m2

Any history of serious allergic/hypersensitivity reactions

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single oral dose of [14C]-EDG-7500 to assess absorption, metabolism, and excretion

1 day

Follow-up

Participants are monitored for safety and pharmacokinetics of EDG-7500 in plasma and 14C-related material in whole blood, plasma, urine, and feces

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• [14C]-EDG-7500

Trial Overview [14C]-EDG-7500 is being tested to see how it's absorbed, metabolized, and excreted after a single dose. The study involves tracking the drug with a radioactive tracer and measuring its presence in blood, urine, and feces.

How Is the Trial Designed?

Group I: Human AME Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Edgewise Therapeutics, Inc.

Lead Sponsor

Trials

13

Recruited

1,000+

Published Research Related to This Trial

PD 0348292 was found to be well tolerated in healthy subjects during phase 1 studies, with only minor bleeding-related adverse events noted after multiple doses, indicating a favorable safety profile.

The drug demonstrated robust inhibition of thrombin generation in a concentration-dependent manner, suggesting its potential efficacy in managing coagulation, with pharmacokinetic properties supporting further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and pharmacodynamics of PD 0348292, an oral, direct factor Xa inhibitor, after single and multiple dosings in healthy subjects. Xuan, D., McBride, S., Wastall, P., et al.[2018]

The study involving 9 healthy volunteers showed that the radioligand 11C-PD153035 is primarily excreted through the renal and hepatobiliary systems, with the urinary bladder receiving the highest radiation-absorbed dose, indicating careful consideration for safety in repeated use.

11C-PD153035 has a favorable radiation dose profile, making it suitable for multiple PET examinations within a year, and it shows promise for investigating EGFR in conditions like non-small cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET-based biodistribution and radiation dosimetry of epidermal growth factor receptor-selective tracer 11C-PD153035 in humans. Liu, N., Li, M., Li, X., et al.[2018]

The study analyzed the distribution kinetics of [(14)C]-edrophonium in normal Wistar and homozygous Gunn rats, revealing that the drug's plasma concentration followed a three-compartment model after intravenous injection.

The route of administration significantly affected the plasma concentration of [(14)C]-edrophonium, with differences noted between systemic venous and hepatic portal routes, while the metabolism rate remained consistent across both rat species despite genetic differences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacokinetics of (14C)-edrophonium in normal wistar rats and homozygous Gunn rats with ligated renal pedicles. Back, DJ., Calvey, TN.[2019]

The PET tracer [68Ga]NODAGA-duramycin specifically binds to areas of cell death, allowing for the non-invasive detection of organ toxicity caused by chemotherapy in mice.

This method demonstrated high sensitivity in identifying organ toxicities earlier than traditional blood tests and immunohistology, suggesting it could be a valuable tool for monitoring chemotherapy effects in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Chemotherapy-Induced Organ Damage with Ga-68 Labeled Duramycin. Rix, A., Drude, NI., Mrugalla, A., et al.[2021]

The study demonstrated that 99mTc-ethylenedicysteine-glucosamine (EC-DG) can effectively assess tumor growth and cell nuclei activity in cancer cells, indicating its potential as a diagnostic tool.

In animal models, 99mTc-EC-DG allowed for clear visualization of tumors and helped evaluate the efficacy of chemotherapy treatments (paclitaxel and cisplatin), showing changes in tumor response correlated with biological markers of treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of therapeutic tumor response using 99mtc-ethylenedicysteine-glucosamine. Yang, D., Yukihiro, M., Yu, DF., et al.[2015]

Vericiguat was well tolerated in a study involving 265 healthy male participants, with no deaths or serious adverse events reported, and common side effects being mild, such as headache and dizziness.

The drug was rapidly absorbed and had a favorable pharmacokinetic profile, with food increasing its bioavailability by 19%, suggesting that it can be effectively administered with meals, supporting its further evaluation for treating heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacodynamic, and pharmacokinetic characterization of vericiguat: results from six phase I studies in healthy subjects. Boettcher, M., Thomas, D., Mueck, W., et al.[2023]

In a study involving 32 healthy volunteers, S-3304 was generally well tolerated at doses up to 2400 mg taken twice daily for 28 days, indicating its safety at these levels.

However, at the highest dose of 3200 mg twice daily, there were significant elevations in alanine aminotransferase (ALT) levels, leading to the withdrawal of five participants, highlighting ALT elevation as a key safety concern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and safety assessments of high-dose and 4-week treatment with S-3304, a novel matrix metalloproteinase inhibitor, in healthy volunteers. Mant, TG., Bradford, D., Amin, DM., et al.[2018]

A systematic review of 34 double-blind randomized controlled trials found that oral intake of L-Arginine (L-Arg) in healthy subjects did not significantly increase the risk of gastrointestinal symptoms, suggesting it is generally safe at various dosages.

The estimated no-observed adverse effect level (NOAEL) for L-Arg was determined to be 7531 mg per one-time dose, indicating a high tolerance for this amino acid in healthy individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety assessment of L-Arg oral intake in healthy subjects: a systematic review of randomized control trials. Kuramochi, Y., Murata, M., Sumino, A., et al.[2023]

Ethylene glycol (EG) is rapidly and almost completely absorbed when administered orally, with a bioavailability of 92-100%, while its absorption through the skin is much slower and less effective, with a bioavailability of about 22%.

The primary elimination route for low doses of EG is through metabolism to carbon dioxide and exhalation, but at higher doses, urinary excretion becomes the main pathway, indicating a dose-dependent shift in how the body processes EG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of ethylene glycol. III. Plasma disposition and metabolic fate after single increasing intravenous, peroral, or percutaneous doses in the male Sprague-Dawley rat. Frantz, SW., Beskitt, JL., Tallant, MJ., et al.[2019]

In a 2-year chronic toxicity study involving Fischer 344 rats, age significantly affected the pharmacokinetics of ethylenediamine (EDA), with older rats showing a two- to threefold increase in the area under the curve (AUC) compared to younger rats, indicating altered drug absorption and distribution with age.

The volume of distribution (Vd) was also notably lower in older rats, being approximately one-fourth to one-half of that in younger rats, suggesting that age impacts how the body processes EDA, while no significant differences were found based on sex or chronic dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Age-dependent pharmacokinetic changes of ethylenediamine in Fischer 344 rats parallel to a two-year chronic toxicity study. Yang, RS., Tallant, MJ., McKelvey, JA.[2019]

Ethylenediamine dihydrochloride (EDA X 2HCl) showed slight to moderate toxicity in laboratory animals, with significant effects observed in body weight gain and organ weights at high doses during short-term studies.

In a 3-month study with Fischer 344 rats, the highest dose of EDA X 2HCl led to marked decreases in body weight and changes in clinical chemistry and organ weights, but no deaths or severe lesions were reported, indicating a need for careful dosing to avoid adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute and subchronic toxicity of ethylenediamine in laboratory animals. Yang, RS., Garman, RH., Maronpot, RR., et al.[2019]

The maximum tolerated doses of 17DMAG were established at 16 mg/m² for a 5-day regimen and 25 mg/m² for a 3-day regimen, with the treatment being generally well tolerated despite some grade 3/4 toxicities like liver function test elevation and pneumonitis.

No objective responses were observed in the study, but four patients experienced stable disease, indicating that while 17DMAG is safe at the recommended doses, its efficacy in producing significant tumor responses needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I pharmacokinetic and pharmacodynamic study of 17-dimethylaminoethylamino-17-demethoxygeldanamycin, an inhibitor of heat-shock protein 90, in patients with advanced solid tumors. Ramanathan, RK., Egorin, MJ., Erlichman, C., et al.[2021]

The study found that 14C-Diethylene glycol (DEG) has a variable elimination half-life in rats, ranging from 6 to 10 hours depending on the dose, with a shift from zero-order to first-order elimination kinetics after certain time intervals, indicating complex metabolism.

Ethylene glycol (EG) also showed a similar elimination pattern with half-lives around 4 hours, and both DEG and EG were found to cause metabolic acidosis, as indicated by changes in urinary pH, highlighting their potential toxicity and the need for careful monitoring in cases of exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and biotransformation of diethylene glycol and ethylene glycol in the rat. Lenk, W., Löhr, D., Sonnenbichler, J.[2019]

In a phase I study involving 30 patients with advanced cancers, 17-AAG was found to have a tolerable toxicity profile, with dose-limiting toxicities including grade 3 diarrhea and hepatotoxicity at the highest dose of 450 mg/m²/week.

The study demonstrated that 17-AAG effectively inhibited target proteins in tumor biopsies and showed some clinical activity, with two patients with metastatic melanoma achieving stable disease for 15 and 41 months, leading to a recommendation of 450 mg/m²/week for phase II trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I pharmacokinetic and pharmacodynamic study of 17-allylamino, 17-demethoxygeldanamycin in patients with advanced malignancies. Banerji, U., O'Donnell, A., Scurr, M., et al.[2022]

In a phase I study involving 24 patients with advanced cancers, CP-751,871 was found to have a favorable safety profile, with mild treatment-related toxicities and no serious adverse events reported.

At the maximum feasible dose of 20 mg/kg, 10 out of 15 patients experienced stability of their disease, indicating potential efficacy, although no objective responses were observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose escalation study of the anti insulin-like growth factor-I receptor monoclonal antibody CP-751,871 in patients with refractory solid tumors. Haluska, P., Shaw, HM., Batzel, GN., et al.[2021]

Citations

1. prnewswire.com prnewswire.com/news-releases/edgewise-therapeutics-announces-positive-top-line-results-from-phase-2-cirrus-hcm-four-week-trial-of-edg-7500-in-hypertrophic-cardiomyopathy-hcm-302417857.html

Edgewise Therapeutics Announces Positive Top-Line ... Treatment with 100 mg of EDG-7500 also demonstrated a 62% mean reduction from baseline in NT-proBNP, a key biomarker of heart failure. In ...

2. edgewisetx.com edgewisetx.com/science-pipeline/edg-7500/

Cardiac Diastolic Dysfunction - EDG-7500 EDG-7500 is a novel oral, selective cardiac sarcomere modulator for the treatment of HCM and other serious diseases of cardiac diastolic dysfunction.

3. nasdaq.com nasdaq.com/press-release/edgewise-therapeutics-announces-positive-top-line-data-phase-1-trial-healthy-subjects

Edgewise Therapeutics Announces Positive Top-Line Data ... In a Phase 1 in healthy subjects, EDG-7500 was well-tolerated without meaningful changes in left ventricle ejection fraction (LVEF) –.

4. emjreviews.com emjreviews.com/cardiology/article/novel-cardiac-sarcomere-modulator-edg-7500-in-hypertrophic-cardiomyopathy-evaluating-new-phase-ii-data-from-cirrus-hcm/

Novel Cardiac Sarcomere Modulator, EDG-7500, in ... Michelle Michels and Perry Elliott discuss the CIRRUS-HCM study of EDG-7500 in hypertrophic cardiomyopathy, highlighting clinical benefits.

5. clinicaltrialsarena.com clinicaltrialsarena.com/news/edgewise-obstructive-hcm-trials/

Edgewise's EDG-7500 shows benefit in two obstructive ... The data comprise results from a Phase I trial in healthy subjects and the single-dose arm of the Phase II CIRRUS-HCM trial. Go deeper with ...

6. synapse.patsnap.com synapse.patsnap.com/article/edgewises-stock-soars-50-after-heart-disease-drug-safety-data

Edgewise's stock soars 50% after heart disease drug safety ... EDG-7500 was tested both in healthy individuals and patients with obstructive HCM, yielding promising results. In healthy subjects, phase 1 ...

7. withpower.com withpower.com/trial/edg-7500-for-healthy-subjects-b91b3

EDG-7500 for Healthy Subjects · Info for Participants What safety data is available for EDG-7500? The provided research does not contain any safety data specifically for EDG-7500 or its variants like [14C]-EDG-7500 ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06347159

NCT06347159 | A Study of EDG-7500 in Adults With ... This study is being conducted in order to understand the safety and effects of different doses of EDG-7500 as a single dose in adults with obstructive ...

9. edgewisetx.com edgewisetx.com/wp-content/uploads/2024/08/HFSA_Clinical_Trial_Row_Poster_Final_Draft_4.1.pdf

A Phase 1, Randomized, Double-blind, Placebo-controlled, ... The purpose of this first-in-human study is to evaluate the initial safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), food effect (FE), and ...