Effect of Probenecid on Pexidartinib Pharmacokinetics

Study Overview
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Brief Summary
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The primary objective of this trial is to assess the effect of probenecid on the pharmacokinetics (PK) of single-dose pexidartinib in healthy subjects. Secondary objectives are to assess the safety and tolerability of pexidartinib alone and in combination with probenecid. Participants will be confined to the clinic for approximately 32 days. Blood samples will be collected for PK analysis of pexidartinib and metabolites at predose and up to 312 hours (h) post dose.

Official Title
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An Open-label, Randomized, 2-treatment, 2-period, Crossover Study to Evaluate the Effect of Probenecid on the Pharmacokinetics of Pexidartinib in Healthy Subjects

Conditions
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Pharmacokinetics in Healthy Volunteers

Intervention / Treatment
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* Drug: Pexidartinib
* Drug: Probenecid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is a healthy, nonsmoking person with a body mass index of 18 kg/m2 to 30 kg/m2 (inclusive) at Screening Is willing to be confined at the clinic for approximately 32 days Is surgically sterile or a naturally postmenopausal female and not lactating, or a male who agrees to use double barrier methods of contraception and avoid donating sperm from Check-in until 90 d after the final dose of pexidartinib Exclusion Criteria: Has any history or condition, per protocol or in the opinion of the investigator, that might compromise the participant's safety, their ability to complete the trial, and or analysis of results

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This is an open-label, 2-treatment sequence, 2-period, crossover study with a washout between doses and treatment periods
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pexidartinib then Probenecid<br>Participants receive Sequence AB: Treatment A (pexidartinib) first, then Treatment B (probenecid), with a washout period between them | Drug: Pexidartinib<br>* Orally, on Day 2<br>* Other names: Treatment A;Drug: Probenecid<br>* Orally, on Day 2<br>* Other names: Treatment B;|
| Experimental: Probenecid then Pexidartinib<br>Participants receive Sequence BA: Treatment B (probenecid) first, then Treatment A (pexidartinib), with a washout period between them | Drug: Pexidartinib<br>* Orally, on Day 2<br>* Other names: Treatment A;Drug: Probenecid<br>* Orally, on Day 2<br>* Other names: Treatment B;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) | Maximum concentration of the drug and its metabolite in plasma | predose to 312 hours post dose | 
| Time to Maximum Concentration (Tmax) | Time at which the maximum concentration is reached | within 312 hours post dose | 
| Area under the curve to the last quantifiable measurement (AUClast) | Area under the drug concentration time curve from the first measurement to the last | within 312 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants experiencing an adverse event | Total number of participants experiencing any adverse event | within 312 hours post dose |