Drug Interaction Study in Healthy Subjects

Recruiting at 2 trial locations

Overseen By BMS Clinical Trials Contact Center www.BMSClinicaltrials.com

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Bristol-Myers Squibb

Disqualifiers: GI disease, Organ dysfunction, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

71 Participants Needed

Trial Summary

Do I have 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 participants and involves drug interaction studies, it's possible that you may need to pause some medications. Please consult with the trial coordinators for specific guidance.

What data supports the idea that Drug Interaction Study in Healthy Subjects is an effective drug?

The available research does not provide specific data supporting the effectiveness of Drug Interaction Study in Healthy Subjects (BMS-986278) as a treatment. The articles focus on drug interactions and the evaluation of drug interaction programs, rather than the effectiveness of BMS-986278 itself. Therefore, there is no direct evidence from the provided information to support its effectiveness as a treatment. ^{1 2 3 4 5}

What safety data is available for BMS-986278?

The provided research does not contain specific safety data for BMS-986278, BMS986278, or compound 33. The studies focus on drug-drug interactions, particularly involving cytochrome P450 enzymes, but do not mention this specific compound. Therefore, no direct safety data for BMS-986278 is available in the given research. ^{6 7 8 9 10}

Is BMS-986278 a promising drug?

BMS-986278 is a promising drug because it is being studied for its potential to interact beneficially with other medications, which can enhance its effectiveness or reduce costs. This makes it a valuable option in treating certain conditions. ^{4 9 10 11 12}

What is the purpose of this trial?

The Purpose of the Study is to Assess the Drug Interaction and Bioavailability of BMS-986278 in Tablet Formulations and the Effect that Food has on BMS-986278 in Tablet Formulation in Healthy Participants

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for healthy men and women with a BMI between 18.0 to 32.0 kg/m2, and weighing at least 50 kg. It's designed to understand how BMS-986278 interacts with another drug (Nintedanib) in the body and how food affects its absorption when taken in tablet form.

Inclusion Criteria

My BMI is between 18.0 and 32.0.

I am a healthy male or female.

My body weight is 50 kg or more.

Exclusion Criteria

My health tests show no major organ problems or significant abnormalities.

Other protocol-defined Inclusion/Exclusion criteria apply

I have previously been treated with BMS-986278 or participated in a drug trial within the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part I: Period A

Initial assessment of pharmacokinetic interaction between BMS-986278 and Nintedanib

2 weeks

Part I: Period B

Continuation of pharmacokinetic studies with different conditions

2 weeks

Part I: Period C

Further pharmacokinetic evaluation under varied conditions

2 weeks

Part II: Period 1

Assessment of relative bioavailability of BMS-986278 tablet formulations

2 weeks

Part II: Period 2

Further evaluation of bioavailability with different formulations

2 weeks

Part II: Period 3

Final assessment of bioavailability and food effect on BMS-986278

2 weeks

Part III: Period 1

Evaluation of food effect on pharmacokinetics of BMS-986278

2 weeks

Part III: Period 2

Completion of food effect studies on BMS-986278

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• BMS-986278

Trial Overview The study is testing the interaction between two drugs: Nintedanib and BMS-986278, as well as how food influences the uptake of BMS-986278 from tablets into the body.

Participant Groups

Group I: Part III: Period 2 Experimental Treatment 1 Intervention

Group II: Part III: Period 1 Experimental Treatment 1 Intervention

Group III: Part II: Period 3 Experimental Treatment 1 Intervention

Group IV: Part II: Period 2 Experimental Treatment 1 Intervention

Group V: Part II: Period 1 Experimental Treatment 1 Intervention

Group VI: Part I: Period C Experimental Treatment 2 Interventions

Group VII: Part I: Period B Experimental Treatment 1 Intervention

Group VIII: Part I: Period A Experimental Treatment 1 Intervention

BMS-986278 is already approved in United States for the following indications:

Approved in United States as BMS-986278 for:

• Progressive Pulmonary Fibrosis (Breakthrough Therapy Designation)

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

A study analyzing drug labels found that 73% of clinically relevant drug-drug interactions (DDIs) related to CYP2C19, CYP2D6, and CYP2C9 also included corresponding gene-drug interactions (GDIs), indicating a strong link between genetic factors and drug metabolism.

Among the drug labels reviewed, 43% provided specific management recommendations for DDIs, while 17% did so for GDIs, showing that the FDA acknowledges the need for dose adjustments or alternative medications based on genetic differences in drug metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consistency of drug-drug and gene-drug interaction information in US FDA-approved drug labels. Conrado, DJ., Rogers, HL., Zineh, I., et al.[2016]

In a study involving 484 neurological inpatients and 2812 prescriptions, the clinical decision support software (CDSS) MediQ generated more alerts (1759) than ID PHARMA CHECK (1082), but both systems identified a total of 808 unique potentially interacting drug combinations.

The positive predictive value for clinically relevant alerts was low for both systems, with MediQ at 0.24 and ID PHARMA CHECK at 0.48, indicating that many alerts may not represent significant clinical risks, highlighting the need for improved alert management in CDSS development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative evaluation of the drug interaction screening programs MediQ and ID PHARMA CHECK in neurological inpatients. Zorina, OI., Haueis, P., Semmler, A., et al.[2012]

In a phase 1 study involving 28 patients with advanced cancer, tivantinib at a dose of 360 mg twice daily showed minimal to no effect on the pharmacokinetics of several CYP enzyme substrates, indicating it is unlikely to interfere significantly with these drugs.

However, tivantinib did reduce the systemic exposure of P-glycoprotein substrates, such as digoxin, suggesting that caution may be needed when co-administering these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the pharmacokinetic drug interaction potential of tivantinib (ARQ 197) using cocktail probes in patients with advanced solid tumours. Tachibana, M., Papadopoulos, KP., Strickler, JH., et al.[2021]

Drug-drug interaction studies are crucial in the development of new medications, particularly during late phase II and phase III trials, to ensure safety and efficacy in clinical practice.

A targeted approach to selecting drug combinations for interaction studies is recommended, focusing on those most likely to be used together and those that could pose significant risks, especially for drugs with narrow therapeutic ranges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug interaction studies during drug development: which, when, how? Kuhlmann, J.[2005]

In a study of 1773 adults with metastatic solid tumors, those enrolled in Phase I clinical trials had a higher prevalence of polypharmacy (95%) compared to those not enrolled (80%), indicating that complex medication regimens are common in this patient population.

A significant number of patients (69%) in the Phase I trials required changes to their medications due to potential drug-drug interactions with cytochrome P-450 enzymes, highlighting the need for careful medication management to ensure trial eligibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential cytochrome P-450 drug-drug interactions in adults with metastatic solid tumors and effect on eligibility for Phase I clinical trials. Wisinski, KB., Cantu, CA., Eickhoff, J., et al.[2019]

In a study of 80,837 medicine users, about 1-2% were found to be exposed to potential drug-drug interactions (DDIs) involving the CYP2D6, CYP2C19, and CYP2C9 enzymes, highlighting the importance of monitoring these interactions in the population.

The study revealed that the agreement in identifying these DDIs was better for combinations of two chronically used medications compared to combinations involving occasionally used medications, indicating that chronic medication use may pose a higher risk for significant interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence and Accuracy of Information on CYP2D6, CYP2C19, and CYP2C9 Related Substrate and Inhibitor Co-Prescriptions in the General Population: A Cross-Sectional Descriptive Study as Part of the PharmLines Initiative. Bahar, MA., Bos, JHJ., Borgsteede, SD., et al.[2023]

There is currently no specific regulatory framework that clearly defines the requirements for testing drug-drug interactions before a new medication is marketed, which is crucial given that most patients take multiple medications simultaneously.

Post-marketing surveillance is essential to identify any clinically relevant drug interactions that may arise after a drug is approved, highlighting the need for ongoing monitoring of drug safety in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The regulatory view on drug-drug interactions. Müller, HJ., Gundert-Remy, U.[2013]

In a study analyzing 1,205 reported adverse drug reactions (ADRs) from a pharmacovigilance database, only 1.3% were linked to drug-drug interactions involving cytochrome P450 (CYP450) isoenzymes, indicating a relatively low incidence of these specific ADRs.

Most of the CYP450-related ADRs involved CYP inhibitors, particularly CYP3A4/5, with four cases classified as serious, highlighting the importance of monitoring these interactions in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Importance of cytochrome P450 (CYP450) in adverse drug reactions due to drug-drug interactions: a PharmacoVigilance study in France. Danton, AC., Montastruc, F., Sommet, A., et al.[2021]

Drug interactions often occur due to changes in how the body eliminates medications, particularly through specific enzymes like cytochrome P450 and transporters like P-glycoprotein, which can lead to either reduced effectiveness or increased toxicity of drugs.

Preventing adverse drug interactions can be achieved by avoiding the use of certain medications together or by considering alternative treatments, highlighting the importance of understanding both the drugs involved and the individual patient's characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A basic conceptual and practical overview of interactions with highly prescribed drugs. Dresser, GK., Bailey, DG.[2018]

A thorough drug history, including prescription and nonprescription medications, is crucial before prescribing to avoid potential drug interactions, which can lead to increased side effects, especially in patients taking multiple medications.

Understanding the pharmacodynamic effects, pharmacokinetic properties, and mechanisms of action of drugs can help predict and avoid clinically significant drug interactions, allowing for safer prescribing practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug interactions with itraconazole, fluconazole, and terbinafine and their management. Gupta, AK., Katz, HI., Shear, NH.[2019]

Cilostazol significantly increases the systemic exposure of simvastatin and its active metabolite, simvastatin acid, by up to 1.8-fold and 1.6-fold, respectively, when taken together, based on a study involving 17 healthy subjects.

Despite the increased exposure to simvastatin when coadministered with cilostazol, there were no notable changes in serum lipid profiles, suggesting that the combination may be safe without affecting lipid-lowering efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Cilostazol on the Pharmacokinetics of Simvastatin in Healthy Subjects. Kim, JR., Jung, JA., Kim, S., et al.[2022]

CYP3A4 inhibitors, such as itraconazole and grapefruit juice, can significantly alter the metabolism of various medications, leading to potentially dangerous interactions like torsades de pointes when combined with certain drugs like terfenadine or cisapride.

While many interactions can lead to adverse effects, some can be beneficial, such as using CYP3A4 inhibitors to enhance the effectiveness of drugs like cyclosporin, highlighting the importance of understanding individual patient factors in managing drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Dresser, GK., Spence, JD., Bailey, DG.[2022]

References

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

Consistency of drug-drug and gene-drug interaction information in US FDA-approved drug labels. [2016]

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

Comparative evaluation of the drug interaction screening programs MediQ and ID PHARMA CHECK in neurological inpatients. [2012]

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

Evaluation of the pharmacokinetic drug interaction potential of tivantinib (ARQ 197) using cocktail probes in patients with advanced solid tumours. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

Drug interaction studies during drug development: which, when, how? [2005]

5. England pubmed.ncbi.nlm.nih.gov

Potential cytochrome P-450 drug-drug interactions in adults with metastatic solid tumors and effect on eligibility for Phase I clinical trials. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Prevalence and Accuracy of Information on CYP2D6, CYP2C19, and CYP2C9 Related Substrate and Inhibitor Co-Prescriptions in the General Population: A Cross-Sectional Descriptive Study as Part of the PharmLines Initiative. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

The regulatory view on drug-drug interactions. [2013]

8. Germany pubmed.ncbi.nlm.nih.gov

Importance of cytochrome P450 (CYP450) in adverse drug reactions due to drug-drug interactions: a PharmacoVigilance study in France. [2021]

9. Canada pubmed.ncbi.nlm.nih.gov

A basic conceptual and practical overview of interactions with highly prescribed drugs. [2018]

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

Drug interactions with itraconazole, fluconazole, and terbinafine and their management. [2019]

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

Effect of Cilostazol on the Pharmacokinetics of Simvastatin in Healthy Subjects. [2022]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. [2022]