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

Phase 1
Completed
Conditions
Healthy Volunteers
Interventions
Drug: Treatment A - 400 mg Fasting
Drug: Treatment B - 400 mg Fed
Drug: Treatment C - 200 mg Fed
Registration Number
NCT03901313
Lead Sponsor
Daiichi Sankyo
Brief Summary

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

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

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
24
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:

    1. containing caffeine/xanthine or alcohol from 48 hours before check-in
    2. 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:

    1. has a clinically significant disorder, disease or lab value
    2. consumes a prohibited drug, drink or food
    3. is unable to consume the standard meal
  • Is an employee of the clinic or their family member

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Sequence ABCTreatment B - 400 mg FedHealthy 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
Sequence ABCTreatment C - 200 mg FedHealthy 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
Sequence ACBTreatment A - 400 mg FastingHealthy 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
Sequence BACTreatment C - 200 mg FedHealthy 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
Sequence BCATreatment A - 400 mg FastingHealthy 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
Sequence BACTreatment B - 400 mg FedHealthy 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
Sequence BCATreatment B - 400 mg FedHealthy 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
Sequence CBATreatment B - 400 mg FedHealthy 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
Sequence BCATreatment C - 200 mg FedHealthy 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
Sequence CABTreatment C - 200 mg FedHealthy 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
Sequence BACTreatment A - 400 mg FastingHealthy 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
Sequence ABCTreatment A - 400 mg FastingHealthy 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
Sequence ACBTreatment B - 400 mg FedHealthy 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
Sequence ACBTreatment C - 200 mg FedHealthy 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
Sequence CBATreatment A - 400 mg FastingHealthy 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
Sequence CABTreatment A - 400 mg FastingHealthy 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
Sequence CBATreatment C - 200 mg FedHealthy 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
Sequence CABTreatment B - 400 mg FedHealthy 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
Primary Outcome Measures
NameTimeMethod
Terminal Half-life (t1/2)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

Mean t1/2 for pexidartinib is calculated for each treatment period

Maximum Observed Concentration in Plasma (Cmax) of PexidartinibBaseline, 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

Mean Cmax of pexidartinib is calculated for each treatment period

Time to Cmax (Tmax)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

Median Tmax of pexidartinib is calculated for each treatment period

Area Under the Concentration-time Curve From Time of Dosing to Last Measurable Concentration (AUClast) and to Infinity (AUCinf)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

Mean AUClast and AUCinf for pexidartinib are calculated for each treatment period

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Worldwide Clinical Trials

🇺🇸

San Antonio, Texas, United States

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