Voriconazole and Quinidine with Repotrectinib for Healthy Subjects

No longer recruiting at 1 trial location

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

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Bristol-Myers Squibb

Disqualifiers: Endocrine, Cardiovascular, Hepatic, Renal, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how two drugs, voriconazole (an antifungal medication) and quinidine (an antiarrhythmic drug), affect the body's processing of another drug, repotrectinib. The goal is to understand how combining these treatments might alter repotrectinib's function in the body. Healthy individuals who cannot have children (due to medical reasons or age) and who do not have significant medical issues might be suitable for this trial. Meeting these criteria and participating could help improve future treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering a chance to contribute to groundbreaking medical research.

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

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team to get a clear answer.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that voriconazole is generally safe and well-tolerated. In studies, some participants experienced mild side effects such as changes in vision, headaches, and dizziness, which typically disappeared within an hour of taking the medication.

Quinidine, however, presents some safety concerns. It can cause heart rhythm problems and stomach issues. Due to these concerns, doctors exercise caution when prescribing it. Always consult your healthcare provider for personal advice. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Voriconazole and Quinidine with Repotrectinib because it represents a novel approach to enhancing drug metabolism and interactions. Unlike standard treatments that focus on a single pathway, this combination aims to optimize the effectiveness of Repotrectinib by leveraging Quinidine’s ability to inhibit specific enzymes, potentially leading to improved drug performance. Voriconazole, an antifungal, plays a unique role by interacting with these pathways, which could provide insights into managing complex drug interactions. This approach could pave the way for more precise and effective treatments, generating significant interest in the medical community.

What evidence suggests that this trial's treatments could be effective?

This trial will examine the effects of Voriconazole and Quinidine combined with Repotrectinib in healthy subjects. Research has shown that Voriconazole effectively treats infections caused by yeasts and molds, with success rates of 77% and 60%, respectively. It is generally well-tolerated, even by individuals with asthma, at certain doses. Quinidine effectively treats irregular heartbeats and malaria, with a strong history of managing atrial fibrillation, a common irregular heartbeat. Both treatments have proven effective in their areas, supporting their use in further studies. ^{1 4 6 7 8}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for healthy adult men and women who cannot become pregnant. Participants must not have any significant health issues that could interfere with the study or be taking medications that might interact with the drugs being tested.

Inclusion Criteria

Healthy male and female individual(s) not of childbearing potential (INOCBP) participants of any race or ethnicity, as determined by no clinically significant findings in medical history, physical examination, 12-lead ECG, or vital signs as determined by the investigator or designee

Potassium, magnesium, and calcium at or above the lower limit of normal. For other clinical laboratory parameters, no clinically significant findings as determined by the investigator or designee

Must have a body mass index between 18 and 30 kg/m2 (inclusive) and body weight ≥ 50 kg at the time of signing the ICF

Exclusion Criteria

I have had GI surgery that may affect how drugs work in my body, except for simple appendix or hernia operations.

I have Gilbert's syndrome.

Other protocol-defined Inclusion/Exclusion criteria apply

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive a single dose of repotrectinib with voriconazole to assess pharmacokinetics

1 week

Treatment Part 2

Participants receive a single dose of repotrectinib with quinidine to assess pharmacokinetics

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Quinidine
• Voriconazole

Trial Overview The study is testing how repotrectinib, a medication, behaves in the body when taken with either voriconazole or quinidine. It's to see if these other drugs change how much repotrectinib gets into the bloodstream and how long it stays there.

How Is the Trial Designed?

Group I: Part 2 Experimental Treatment 2 Interventions

Group II: Part 1 Experimental Treatment 2 Interventions

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

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK542193/

Quinidine - StatPearls - NCBI Bookshelf Quinidine is a medication primarily utilized to manage and treat specific arrhythmias and malaria in patients.

2. sciencedirect.com sciencedirect.com/science/article/pii/S1050173824000616

Quinidine for ventricular arrhythmias: A comprehensive ... Upon confirmation through ECG, it was evident that the drug was effective for treatment of atrial fibrillation (AF) [2,3]. In 1918, Frey [4] demonstrated that ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/3512148/

Effects of quinidine on pharmacokinetics and ... Quinidine has been reported to increase digoxin plasma concentrations, which increases the risk of digoxin overdose. The effect of quinidine on digitoxin ...

4. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D3820C00011

Study in healthy volunteers to investigate the effects of ... Study in healthy volunteers to investigate the effects of Quinidine on the Pharmacokinetics of NKTR-118.

5. ascpt.onlinelibrary.wiley.com ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.3156

Assessment of Quinidine‐Induced Torsades de Pointes Risks ... The results showed that most of the observed plasma quinidine concentrations fell between the simulated 5th and 95th percentiles (Figure 2), ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2010/089338s036lbl.pdf

QUINIDINE_GLUCONATE_8_09.ps - accessdata.fda.gov Safety and efficacy of quinidine in elderly patients have not been systematically studied. Pediatric use. In antimalarial trials, quinidine ...

7. carlroth.com carlroth.com/medias/SDB-3348-GB-EN.pdf?context=bWFzdGVyfHNlY3VyaXR5RGF0YXNoZWV0c3wyNDA0MzZ8YXBwbGljYXRpb24vcGRmfGFETXdMMmcyWmk4NU1UZ3pNREE1TWpjMU9UTTBMMU5FUWw4ek16UTRYMGRDWDBWT0xuQmtaZ3xmZTk0ZTFlM2ZkYmE0ZDAzZjU3NTc4MzFhMDIyNTU3MzJlZDFiNWJjYmYyODk5ZWIxMTFhNjdmZGRlOWNlOGFl

Safety Data Sheet: Quinidine sulphate dihydrate Uses advised against: Do not use for private purposes (household). Food, drink and animal feedingstuffs. 1.3. Details of the supplier of the safety data sheet.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02171624

Safety and Pharmacokinetics of Quinidine Alone and in ... Healthy male and female subjects; Age ≥18 and Age ≤55 years; Body Mass Index (BMI) ≥18.5 and BMI <30 kg/m2; Signed and dated written ...