Study to Evaluate the Effect of Repotrectinib on the Drug Levels of Transporter and CYP P450 Probe Substrates in Healthy Adult Participants

Phase 1, 2-Cohort, Open-label, Fixed-sequence, Drug-drug Interaction Study to Evaluate the Effect of Repotrectinib on the Pharmacokinetics of Transporter and CYP P450 Probe Substrates in Healthy Adult Participants

The purpose of the study if to evaluate the effect of Repotrectinib on the drug levels of transporter and CYP P450 probe substrates in healthy adult participants.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Rosuvastatin; Drug: Metformin; Drug: Digoxin; Drug: Flurbiprofen; Drug: Omeprazole; Drug: Bupropion; Drug: Repotrectinib

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117-5116
      • Local Institution - 0001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria

• Participants must have a body mass index (BMI) of 18.0 to 32.0 kg/m2 and should be between the ages of 18-60 years inclusive.
• Healthy female (as assigned at birth) participants who are individuals not of childbearing potential (INOCBP) and healthy males with no clinically significant deviation from normal for the following: medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory assessment results as determined by the investigator.

Exclusion Criteria

• Participants must not have a significant history of clinical manifestation of any metabolic, allergic, dermatological, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, psychiatric, neoplastic, or genitourinary abnormalities/diseases as determined by the investigator or designee.
• Other protocol-defined Inclusion/Exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1	Drug: Rosuvastatin; Specified dose on specified days; Drug: Metformin; Specified dose on specified days; Drug: Digoxin; Specified dose on specified days; Drug: Repotrectinib; Specified dose on specified days
Experimental: Cohort 2	Drug: Flurbiprofen; Specified dose on specified days; Drug: Omeprazole; Specified dose on specified days; Drug: Bupropion; Specified dose on specified days; Drug: Repotrectinib; Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort 1: Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration of AUC (0-T) of Probe Substrate With Repotrectinib	Probe substrate contains metformin, digoxin, and rosuvastatin.	Up to approximately Day 17 post dose
Cohort 1: AUC (0-T) of Probe Substrate Without Repotrectinib	Probe substrate contains metformin, digoxin, and rosuvastatin.	Up to approximately Day 17 post dose
Cohort 1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) of Probe Substrate With Repotrectinib	Probe substrate contains metformin, digoxin, and rosuvastatin.	Up to approximately Day 17 post dose
Cohort 1: AUC(INF) of Probe Substrate Without Repotrectinib	Probe substrate contains metformin, digoxin, and rosuvastatin.	Up to approximately Day 17 post dose
Cohort 1: Maximum Observed Plasma Concentration (Cmax) of Probe Substrate With Repotrectinib	Probe substrate contains metformin, digoxin, and rosuvastatin	Up to approximately Day 17 post dose
Cohort 1: Cmax of Probe Substrate Without Repotrectinib	Probe substrate contains metformin, digoxin, and rosuvastatin	Up to approximately Day 17 post dose
Cohort 1: Area Under the Plasma Concentration-time Curve From Time Zero to 48 Hours Post Dose (AUC (0-48)) of Metformin With Repotrectinib		Up to approximately Day 17 post dose
Cohort 1: AUC (0-48) of Metformin Without Repotrectinib		Up to approximately Day 17 post dose
Cohort 1: Renal Clearance (CLR) of Metformin in Urine		Up to approximately Day 16 post dose
Cohort 2: AUC (0-T) of Probe Substrate With Repotrectinib	Probe substrate contains bupropion, hydroxybupropion, flurbiprofen, 4'-hydroxyflurbiprofen, omeprazole, 5'- hydroxyomeprazole)	Up to approximately Day 17 post dose
Cohort 2: AUC (0-T) of Probe Substrate Without Repotrectinib	Probe substrate contains bupropion, hydroxybupropion, flurbiprofen, 4'-hydroxyflurbiprofen, omeprazole, 5'- hydroxyomeprazole)	Up to approximately Day 17 post dose
Cohort 2: AUC (INF) of Probe Substrate With Repotrectinib	Probe substrate contains bupropion, hydroxybupropion, flurbiprofen, 4'-hydroxyflurbiprofen, omeprazole, 5'- hydroxyomeprazole)	Up to approximately Day 17 post dose
Cohort 2: AUC (INF) of Probe Substrate Without Repotrectinib	Probe substrate contains bupropion, hydroxybupropion, flurbiprofen, 4'-hydroxyflurbiprofen, omeprazole, 5'- hydroxyomeprazole)	Up to approximately Day 17 post dose
Cohort 2: Cmax of Probe Substrate With Repotrectinib	Probe substrate contains bupropion, hydroxybupropion, flurbiprofen, 4'-hydroxyflurbiprofen, omeprazole, 5'- hydroxyomeprazole)	Up to approximately Day 17 post dose
Cohort 2: Cmax of Probe Substrate Without Repotrectinib	Probe substrate contains bupropion, hydroxybupropion, flurbiprofen, 4'-hydroxyflurbiprofen, omeprazole, 5'- hydroxyomeprazole)	Up to approximately Day 17 post dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Adverse Events (AEs)	Up to approximately Day 45 post dose
Number of Participants with Serious Adverse Events (SAEs)	Up to approximately Day 45 post dose
Number of Participants With Clinically Significant Physical Examination Findings	Up to approximately Day 17 post dose
Number of Participants With Clinically Significant Vital Sign Measurements	Up to approximately Day 17 post dose
Number of Participants With Clinically Significant 12-lead Electrocardiogram (12-lead ECG) Findings	Up to approximately Day 17 post dose
Number of Participants With Clinically Significant Safety Laboratory Test Results	Up to approximately Day 17 post dose

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): December 31, 2025
• Primary Completion (Actual): February 19, 2026
• Study Completion (Actual): March 19, 2026

Study Registration Dates

• First Submitted: October 30, 2025
• First Submitted That Met QC Criteria: October 30, 2025
• First Posted (Actual): November 3, 2025

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Drug-Drug Interactions; Transporter Probe Substrates; CYP P450 Probe Substrates
• Additional Relevant MeSH Terms: 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Acids, Acyclic; Carboxylic Acids; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Amides; Pyrimidines; Steroids; Fused-Ring Compounds; Benzene Derivatives; Hydrocarbons, Halogenated; Biguanides; Guanidines; Amidines; Sulfonamides; Sulfones; Ketones; Fluorobenzenes; Hydrocarbons, Fluorinated; Propionates; Biphenyl Compounds; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Propiophenones; Rosuvastatin Calcium; Digoxin; Metformin; Omeprazole; Bupropion; Flurbiprofen; repotrectinib
• Other Study ID Numbers: CA127-1088

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myer Squibb's data sharing policy and process can be found at https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
• IPD Sharing Time Frame: See Plan Description
• IPD Sharing Access Criteria: See Plan Description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No