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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Treatment A - 400 mg Fasting; Drug: Treatment B - 400 mg Fed; Drug: Treatment C - 200 mg Fed

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

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78217
      • Worldwide Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence ABC; 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; Single oral 400 mg (2 × 200 mg capsules) dose of pexidartinib in the morning under fasting conditions; Other Names: Pexidartinib; Drug: Treatment B - 400 mg Fed; 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; Other Names: Pexidartinib; Drug: Treatment C - 200 mg Fed; Single oral 200 mg (1 × 200 mg capsule) dose of pexidartinib in the morning within 30 min after a low-fat standard breakfast meal; Other Names: Pexidartinib
Experimental: Sequence ACB; 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; Single oral 400 mg (2 × 200 mg capsules) dose of pexidartinib in the morning under fasting conditions; Other Names: Pexidartinib; Drug: Treatment B - 400 mg Fed; 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; Other Names: Pexidartinib; Drug: Treatment C - 200 mg Fed; Single oral 200 mg (1 × 200 mg capsule) dose of pexidartinib in the morning within 30 min after a low-fat standard breakfast meal; Other Names: Pexidartinib
Experimental: Sequence BAC; 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; Single oral 400 mg (2 × 200 mg capsules) dose of pexidartinib in the morning under fasting conditions; Other Names: Pexidartinib; Drug: Treatment B - 400 mg Fed; 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; Other Names: Pexidartinib; Drug: Treatment C - 200 mg Fed; Single oral 200 mg (1 × 200 mg capsule) dose of pexidartinib in the morning within 30 min after a low-fat standard breakfast meal; Other Names: Pexidartinib
Experimental: Sequence BCA; 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; Single oral 400 mg (2 × 200 mg capsules) dose of pexidartinib in the morning under fasting conditions; Other Names: Pexidartinib; Drug: Treatment B - 400 mg Fed; 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; Other Names: Pexidartinib; Drug: Treatment C - 200 mg Fed; Single oral 200 mg (1 × 200 mg capsule) dose of pexidartinib in the morning within 30 min after a low-fat standard breakfast meal; Other Names: Pexidartinib
Experimental: Sequence CAB; 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; Single oral 400 mg (2 × 200 mg capsules) dose of pexidartinib in the morning under fasting conditions; Other Names: Pexidartinib; Drug: Treatment B - 400 mg Fed; 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; Other Names: Pexidartinib; Drug: Treatment C - 200 mg Fed; Single oral 200 mg (1 × 200 mg capsule) dose of pexidartinib in the morning within 30 min after a low-fat standard breakfast meal; Other Names: Pexidartinib
Experimental: Sequence CBA; 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; Single oral 400 mg (2 × 200 mg capsules) dose of pexidartinib in the morning under fasting conditions; Other Names: Pexidartinib; Drug: Treatment B - 400 mg Fed; 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; Other Names: Pexidartinib; Drug: Treatment C - 200 mg Fed; Single oral 200 mg (1 × 200 mg capsule) dose of pexidartinib in the morning within 30 min after a low-fat standard breakfast meal; Other Names: Pexidartinib

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Actual): May 8, 2019
• Study Completion (Actual): May 22, 2019

Study Registration Dates

• First Submitted: April 1, 2019
• First Submitted That Met QC Criteria: April 1, 2019
• First Posted (Actual): April 3, 2019

Study Record Updates

• Last Update Posted (Actual): May 11, 2020
• Last Update Submitted That Met QC Criteria: April 22, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Pharmacokinetics
• Other Study ID Numbers: PL3397-A-U128

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (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