BMS-986365 for Healthy Subjects

Recruiting at 1 trial location

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

Age: 18 - 65

Sex: Male

Trial Phase: Phase 1

Sponsor: Celgene

Disqualifiers: Heart failure, Ischemic heart diseases, Arrhythmias, others

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

Compensation: Varies

Number of Visits: Unknown

24 Participants Needed

Trial Summary

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

The trial protocol does not specify if 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 significant medications. Please consult with the trial coordinators for more details.

What data supports the idea that BMS-986365 for Healthy Subjects is an effective treatment?

The available research does not provide any specific data on the effectiveness of BMS-986365 for Healthy Subjects. Instead, it discusses other treatments for glioblastoma, a type of brain tumor. For example, cilengitide is mentioned as a treatment that may help when combined with another drug, temozolomide, but there is no mention of BMS-986365 in the context of treating glioblastoma or any other condition. ^{1 2 3 4 5}

What safety data is available for BMS-986365, also known as CC-94676 or Gridegalutamide?

The provided research does not contain any safety data for BMS-986365, CC-94676, or Gridegalutamide. The studies mentioned focus on different compounds, such as BMS-986001, SAR425899, MK-5046, BMS-275183, and semaglutide, none of which are related to BMS-986365 or its other names. ^{6 7 8 9 10}

Is the drug BMS-986365 a promising treatment for healthy subjects?

The information provided does not include any details about BMS-986365, so we cannot determine if it is a promising treatment for healthy subjects based on the given research articles. ^{6 7 11 12 13}

What is the purpose of this trial?

The objective of this study is to assess the pharmacokinetics (PK) and absolute bioavailability of BMS-986365 and to investigate the PK, metabolite profile, routes and extent of elimination, and mass balance of BMS-986365.

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for healthy male participants. Specific eligibility criteria are not provided, but typically such studies require individuals without significant health issues who can comply with the study requirements.

Inclusion Criteria

Participants will require a left ventricular ejection fraction of > 50% at screening

Healthy male participants as determined by no clinically significant deviations from normal in medical history, physical examination, 12-lead ECGs, or clinical laboratory determinations, as determined by the investigator

My BMI is between 18.0 and 32.0.

Exclusion Criteria

I do not have any serious illnesses right now.

History of allergy to BMS-986365 or related compounds

I have a history of serious heart conditions or a long QT interval.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part A

Assessment of pharmacokinetics and absolute bioavailability of BMS-986365

Up to 15 days

Multiple visits (in-person)

Part B

Investigation of PK, metabolite profile, routes and extent of elimination, and mass balance of BMS-986365

Up to 60 days

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• BMS-986365

Trial Overview The study is testing BMS-986365 and related compounds to understand how they're processed in the body (pharmacokinetics), their availability when taken orally (bioavailability), and how they're eliminated from the body.

Participant Groups

Group I: Part B - Arm 2 Experimental Treatment 1 Intervention

Group II: Part B - Arm 1 Experimental Treatment 1 Intervention

Group III: Part A Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Celgene

Lead Sponsor

Trials

649

Recruited

130,000+

Top Products

>- **Revlimid (lenalidomide)**: Multiple myeloma, myelodysplastic syndromes, and mantle cell lymphoma treatment. - **Pomalyst (pomalidomide)**: Relapsed/refractory multiple myeloma treatment. - **Otezla (apremilast)**: Psoriatic arthritis treatment. - **Thalomid (thalidomide)**: Erythema nodosum leprosum and multiple myeloma treatment.

Jay Backstrom

Celgene

Chief Medical Officer since 2016

MD

Mark Alles

Celgene

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Findings from Research

DTCM-g, a new anti-inflammatory compound, effectively impairs the growth and invasion of glioblastoma (GBM) cells in both pediatric and adult models, showing potential as an adjuvant treatment.

The compound also enhances the effectiveness of radiation therapy, indicating that it could improve treatment outcomes for GBM patients when used in combination with existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DTCM-glutarimide Delays Growth and Radiosensitizes Glioblastoma. Roberto, GM., Paiva, HH., Botelho de Souza, LE., et al.[2019]

In a phase II trial involving 31 patients with recurrent glioblastoma multiforme, glufosfamide demonstrated modest toxicity but did not show significant clinical antitumor activity, with no objective responses observed.

Only one patient (3%) remained progression-free at 6 months, indicating that glufosfamide may not be an effective treatment option for this type of brain cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European Organization for Research and Treatment of Cancer (EORTC) open label phase II study on glufosfamide administered as a 60-minute infusion every 3 weeks in recurrent glioblastoma multiforme. van den Bent, MJ., Grisold, W., Frappaz, D., et al.[2022]

The bombesin/GRP antagonists RC-3940-II and RC-3940-Et significantly reduced the growth of U-118MG human malignant glioma tumors in nude mice by 52.5% and 72.6%, respectively, over 6 weeks of treatment.

Both antagonists effectively induced apoptosis in tumor cells, as evidenced by a 70% reduction in the Bcl-2:Bax ratio and a significant decrease in VEGF and PKC-alpha levels, suggesting their potential as effective treatments for glioblastomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antagonists of bombesin/gastrin-releasing peptide decrease the expression of angiogenic and anti-apoptotic factors in human glioblastoma. Kanashiro, CA., Schally, AV., Cai, RZ., et al.[2019]

Cilengitide, a cyclic peptide targeting integrins, shows potential as a treatment for glioblastoma, primarily through antiangiogenic effects, but its impact on glioma cell detachment and viability varies across different cell lines.

Preliminary clinical results suggest that cilengitide may enhance the effectiveness of temozolomide-based therapy in patients with specific genetic markers (MGMT promoter methylation), possibly by improving drug delivery to tumor cells rather than directly affecting cell death or migration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cilengitide modulates attachment and viability of human glioma cells, but not sensitivity to irradiation or temozolomide in vitro. Maurer, GD., Tritschler, I., Adams, B., et al.[2021]

Cilengitide (CGT) showed greater sensitivity in treating glioblastoma multiforme (GBM) compared to temozolomide (TMZ) in patient-derived cell lines, indicating its potential as a more effective treatment option.

The combination of CGT with TMZ enhanced tumor growth inhibition specifically in GBM cell lines with a methylated MGMT promoter, suggesting that this combination could be particularly beneficial for certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cilengitide response in ultra-low passage glioblastoma cell lines: relation to molecular markers. Mullins, CS., Schubert, J., Schneider, B., et al.[2021]

BMS-986001 was found to be safe and well tolerated in a study involving 64 healthy male subjects, with no serious adverse events reported and only 14.6% experiencing mild adverse effects that were not dose-related.

The pharmacokinetics of BMS-986001 showed a linear dose-exposure relationship, indicating consistent absorption and effectiveness across various doses, regardless of whether it was taken with or without food.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, placebo-controlled single-ascending-dose study to evaluate the safety, tolerability and pharmacokinetics of the HIV nucleoside reverse transcriptase inhibitor, BMS-986001, in healthy subjects. Urata, Y., Paintsil, E., Cheng, YC., et al.[2014]

MK-5046, a selective agonist for the BRS-3 receptor, was found to be safe and tolerable in a study involving healthy and obese male volunteers, with doses ranging from 10 to 160 mg.

The drug caused transient increases in blood pressure and some mild side effects, such as feelings of warmth and erections, but did not significantly affect hunger or glucose levels, indicating its potential for further exploration in obesity treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of MK-5046, a bombesin receptor subtype-3 (BRS-3) agonist, in healthy patients. Reitman, ML., Dishy, V., Moreau, A., et al.[2021]

In a study involving 2117 participants treated with semaglutide 2.4 mg for 68 weeks, gastrointestinal adverse events (AEs) like nausea and diarrhea were more common than in the placebo group, but these AEs were mostly mild and transient, with only 4.3% of participants discontinuing treatment due to them.

Weight loss with semaglutide was significant and similar in participants with and without GI AEs, indicating that the weight loss effects of semaglutide are largely independent of these gastrointestinal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss. Wharton, S., Calanna, S., Davies, M., et al.[2022]

SAR425899, a dual agonist for GLP-1R and GCR, was well tolerated in clinical trials, with gastrointestinal side effects being less severe in patients with type 2 diabetes compared to healthy volunteers.

The treatment significantly lowered fasting plasma glucose and glycated hemoglobin levels in patients with type 2 diabetes, and also resulted in notable weight loss in both healthy volunteers (up to 5.32 kg) and patients with type 2 diabetes (up to 5.46 kg) compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel dual glucagon-like peptide and glucagon receptor agonist SAR425899: Results of randomized, placebo-controlled first-in-human and first-in-patient trials. Tillner, J., Posch, MG., Wagner, F., et al.[2019]

BMS-275183, a new oral cancer treatment, was found to be generally well tolerated, with a maximum tolerated dose (MTD) established at 200 mg/m2, primarily due to side effects like peripheral neuropathy, fatigue, and neutropenia.

The drug showed promising antitumor activity, with tumor responses observed in 9 out of 38 patients with various cancers, leading to the initiation of a phase II trial specifically for non-small cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial with BMS-275183, a novel oral taxane with promising antitumor activity. Bröker, LE., de Vos, FY., van Groeningen, CJ., et al.[2016]

BMS-275183, an oral paclitaxel analogue, showed a significant decrease in peak drug concentration when taken with food, specifically a 39% reduction with a low-fat meal and a 63% reduction with a high-fat meal, but overall drug exposure remained unchanged.

The study suggests that BMS-275183 can be administered using a flat fixed dose rather than adjusting for body surface area, simplifying dosing while maintaining safety, as it was well tolerated with only a few cases of severe toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of food on the pharmacokinetic behavior of the potent oral taxane BMS-275183. Bröker, LE., Valdivieso, M., Pilat, MJ., et al.[2016]

BMS-181101, a new antidepressant, was well tolerated in a study involving 12 healthy male volunteers, showing that it can be safely administered with or without food.

When taken with food, BMS-181101 had a 25% reduction in peak concentration (Cmax) and a 1-hour delay in the time to reach peak concentration (tmax), but overall pharmacokinetic profiles, including steady state achievement, were not significantly affected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of effect of food on the steady state pharmacokinetics of BMS-181101, an antidepressant, in healthy subjects. Srinivas, NR., Shyu, WC., Lee, J., et al.[2019]

BMS-955176 is a second-generation HIV-1 maturation inhibitor that shows potent activity against a wide range of HIV-1 variants, with an effective concentration (EC50) of 3.9 nM against engineered viruses and 21 nM against clinical isolates, indicating its strong potential as a treatment option.

This compound works by inhibiting HIV-1 protease cleavage at a critical site in the virus's replication cycle and has shown no antagonistic interactions with other antiretroviral drugs, suggesting it could be effectively combined with existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification and Characterization of BMS-955176, a Second-Generation HIV-1 Maturation Inhibitor with Improved Potency, Antiviral Spectrum, and Gag Polymorphic Coverage. Nowicka-Sans, B., Protack, T., Lin, Z., et al.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

DTCM-glutarimide Delays Growth and Radiosensitizes Glioblastoma. [2019]

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

European Organization for Research and Treatment of Cancer (EORTC) open label phase II study on glufosfamide administered as a 60-minute infusion every 3 weeks in recurrent glioblastoma multiforme. [2022]

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

Antagonists of bombesin/gastrin-releasing peptide decrease the expression of angiogenic and anti-apoptotic factors in human glioblastoma. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Cilengitide modulates attachment and viability of human glioma cells, but not sensitivity to irradiation or temozolomide in vitro. [2021]

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

Cilengitide response in ultra-low passage glioblastoma cell lines: relation to molecular markers. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Randomized, placebo-controlled single-ascending-dose study to evaluate the safety, tolerability and pharmacokinetics of the HIV nucleoside reverse transcriptase inhibitor, BMS-986001, in healthy subjects. [2014]

7. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of MK-5046, a bombesin receptor subtype-3 (BRS-3) agonist, in healthy patients. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss. [2022]

9. England pubmed.ncbi.nlm.nih.gov

A novel dual glucagon-like peptide and glucagon receptor agonist SAR425899: Results of randomized, placebo-controlled first-in-human and first-in-patient trials. [2019]

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

Phase I trial with BMS-275183, a novel oral taxane with promising antitumor activity. [2016]

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

Effect of food on the pharmacokinetic behavior of the potent oral taxane BMS-275183. [2016]

12. England pubmed.ncbi.nlm.nih.gov

Lack of effect of food on the steady state pharmacokinetics of BMS-181101, an antidepressant, in healthy subjects. [2019]

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

Identification and Characterization of BMS-955176, a Second-Generation HIV-1 Maturation Inhibitor with Improved Potency, Antiviral Spectrum, and Gag Polymorphic Coverage. [2022]