Effect of Low-Fat Food on Pexidartinib Pharmacokinetics in Healthy Volunteers

Study Overview
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Brief Summary
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All participants in this study are healthy volunteers. Throughout the study, healthy volunteers will have physical exams, electrocardiograms and clinical laboratory tests. The study staff will keep track of symptoms, diet, and what medications they are taking. Each participant will get all three treatments (A, B and C). Only the order in which they receive them will be different. There are six groups based on the order: ABC, ACB, BAC, BCA, CAB, or CBA. Participants have an equal chance of being assigned to any of these groups. For each treatment period, participants will: fast overnight receive the assigned treatment with or without food have a small tube of blood drawn prior to treatment after dosing, additional blood samples will be drawn at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 14, 22, 24, 28, 32, 36, 48, 54, 60, 72, 84, 96, 108, 120, 132, and 144 hours have a break from treatment for 6 days between each treatment period All participants must reside in the clinic for a total of 20 days.

Detailed Description
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The primary objectives of this study are: To assess the effect of low-fat food on the pharmacokinetics (PK) of pexidartinib following a single oral dose of 400 mg administered in healthy subjects To assess the PK of pexidartinib following a single oral dose of 200 mg administered with low-fat food in healthy subjects The secondary objective of this study is: To characterize the safety and tolerability of pexidartinib in healthy subjects following administration of a single oral dose of pexidartinib with low fat food and without food

Official Title
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A Phase 1, Open-Label, Randomized, 3-Period Crossover Study to Assess the Effect of Low-Fat Food on Pexidartinib Pharmacokinetics in Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Treatment A - 400 mg Fasting
* Drug: Treatment B - 400 mg Fed
* Drug: Treatment C - 200 mg Fed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is healthy at screening visit Is not pregnant or lactating Is surgically or naturally unable to reproduce, or agrees to remain sexually abstinent or to use double barrier methods of contraception from check-in until 90 days after the final dose of pexidartinib Has a Body Mass Index (BMI) of 18-30 kg/m^2, inclusive Has negative test results for protocol-defined drugs and diseases at screening and/or check-in Is willing to avoid food or beverages before check-in until the end of the study: containing caffeine/xanthine or alcohol from 48 hours before check-in containing grapefruit or Seville oranges 6 days before check-in Exclusion Criteria: Per protocol or in the opinion of the investigator at screening and/or check-in, has something that would preclude participation: has a clinically significant disorder, disease or lab value consumes a prohibited drug, drink or food is unable to consume the standard meal Is an employee of the clinic or their family member

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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence ABC<br>Healthy volunteers will receive Treatments A, then B, and then C, with a 6-day washout between treatments, during a stay at the clinic of 20 days | Drug: Treatment A - 400 mg Fasting<br>* Single oral 400 mg (2 × 200 mg capsules) dose of pexidartinib in the morning under fasting conditions<br>* Other names: Pexidartinib;Drug: Treatment B - 400 mg Fed<br>* Single oral 400 mg (2 × 200 mg capsules) dose of pexidartinib in the morning within 30 minutes (min) after a low-fat standard breakfast meal<br>* Other names: Pexidartinib;Drug: Treatment C - 200 mg Fed<br>* Single oral 200 mg (1 × 200 mg capsule) dose of pexidartinib in the morning within 30 min after a low-fat standard breakfast meal<br>* Other names: Pexidartinib;|
| Experimental: Sequence ACB<br>Healthy volunteers will receive Treatments A, then C, and then B, with a 6-day washout between treatments, during a stay at the clinic of 20 days | Drug: Treatment A - 400 mg Fasting<br>* Single oral 400 mg (2 × 200 mg capsules) dose of pexidartinib in the morning under fasting conditions<br>* Other names: Pexidartinib;Drug: Treatment B - 400 mg Fed<br>* Single oral 400 mg (2 × 200 mg capsules) dose of pexidartinib in the morning within 30 minutes (min) after a low-fat standard breakfast meal<br>* Other names: Pexidartinib;Drug: Treatment C - 200 mg Fed<br>* Single oral 200 mg (1 × 200 mg capsule) dose of pexidartinib in the morning within 30 min after a low-fat standard breakfast meal<br>* Other names: Pexidartinib;|
| Experimental: Sequence BAC<br>Healthy volunteers will receive Treatments B, then A, and then C, with a 6-day washout between treatments, during a stay at the clinic of 20 days | Drug: Treatment A - 400 mg Fasting<br>* Single oral 400 mg (2 × 200 mg capsules) dose of pexidartinib in the morning under fasting conditions<br>* Other names: Pexidartinib;Drug: Treatment B - 400 mg Fed<br>* Single oral 400 mg (2 × 200 mg capsules) dose of pexidartinib in the morning within 30 minutes (min) after a low-fat standard breakfast meal<br>* Other names: Pexidartinib;Drug: Treatment C - 200 mg Fed<br>* Single oral 200 mg (1 × 200 mg capsule) dose of pexidartinib in the morning within 30 min after a low-fat standard breakfast meal<br>* Other names: Pexidartinib;|
| Experimental: Sequence BCA<br>Healthy volunteers will receive Treatments B, then C, and then A, with a 6-day washout between treatments, during a stay at the clinic of 20 days | Drug: Treatment A - 400 mg Fasting<br>* Single oral 400 mg (2 × 200 mg capsules) dose of pexidartinib in the morning under fasting conditions<br>* Other names: Pexidartinib;Drug: Treatment B - 400 mg Fed<br>* Single oral 400 mg (2 × 200 mg capsules) dose of pexidartinib in the morning within 30 minutes (min) after a low-fat standard breakfast meal<br>* Other names: Pexidartinib;Drug: Treatment C - 200 mg Fed<br>* Single oral 200 mg (1 × 200 mg capsule) dose of pexidartinib in the morning within 30 min after a low-fat standard breakfast meal<br>* Other names: Pexidartinib;|
| Experimental: Sequence CAB<br>Healthy volunteers will receive Treatments C, then A, and then B, with a 6-day washout between treatments, during a stay at the clinic of 20 days | Drug: Treatment A - 400 mg Fasting<br>* Single oral 400 mg (2 × 200 mg capsules) dose of pexidartinib in the morning under fasting conditions<br>* Other names: Pexidartinib;Drug: Treatment B - 400 mg Fed<br>* Single oral 400 mg (2 × 200 mg capsules) dose of pexidartinib in the morning within 30 minutes (min) after a low-fat standard breakfast meal<br>* Other names: Pexidartinib;Drug: Treatment C - 200 mg Fed<br>* Single oral 200 mg (1 × 200 mg capsule) dose of pexidartinib in the morning within 30 min after a low-fat standard breakfast meal<br>* Other names: Pexidartinib;|
| Experimental: Sequence CBA<br>Healthy volunteers will receive Treatments C, then B, and then A, with a 6-day washout between treatments, during a stay at the clinic of 20 days | Drug: Treatment A - 400 mg Fasting<br>* Single oral 400 mg (2 × 200 mg capsules) dose of pexidartinib in the morning under fasting conditions<br>* Other names: Pexidartinib;Drug: Treatment B - 400 mg Fed<br>* Single oral 400 mg (2 × 200 mg capsules) dose of pexidartinib in the morning within 30 minutes (min) after a low-fat standard breakfast meal<br>* Other names: Pexidartinib;Drug: Treatment C - 200 mg Fed<br>* Single oral 200 mg (1 × 200 mg capsule) dose of pexidartinib in the morning within 30 min after a low-fat standard breakfast meal<br>* Other names: Pexidartinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Concentration in Plasma (Cmax) of Pexidartinib | Mean Cmax of pexidartinib is calculated for each treatment period | Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 14, 22, 24, 28, 32, 36, 48, 54, 60, 72, 84, 96, 108, 120, 132, and 144 hours postdose | 
| Time to Cmax (Tmax) | Median Tmax of pexidartinib is calculated for each treatment period | Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 14, 22, 24, 28, 32, 36, 48, 54, 60, 72, 84, 96, 108, 120, 132, and 144 hours postdose | 
| Area Under the Concentration-time Curve From Time of Dosing to Last Measurable Concentration (AUClast) and to Infinity (AUCinf) | Mean AUClast and AUCinf for pexidartinib are calculated for each treatment period | Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 14, 22, 24, 28, 32, 36, 48, 54, 60, 72, 84, 96, 108, 120, 132, and 144 hours postdose | 
| Terminal Half-life (t1/2) | Mean t1/2 for pexidartinib is calculated for each treatment period | Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 14, 22, 24, 28, 32, 36, 48, 54, 60, 72, 84, 96, 108, 120, 132, and 144 hours postdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics