Healthy Volunteers
Conditions
Keywords
Pharmacokinetics
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
Interventions
DRUGTreatment A - 400 mg Fasting
Single oral 400 mg (2 × 200 mg capsules) dose of pexidartinib in the morning under fasting conditions
DRUGTreatment 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
DRUGTreatment 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
Sponsors
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Concentration in Plasma (Cmax) of Pexidartinib | 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 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 |
| 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 |
Countries
United States
Participant flow
Recruitment details
A total of 24 participants who met all inclusion criteria and no exclusion criteria were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Healthy volunteers randomized to receive 1 of 6 sequences of Treatment A, B, and C, with a 6-day washout between treatments, during a stay at the clinic of 20 days
Treatment A - 400 mg Fasting: Single oral 400 mg (2 × 200 mg capsules) dose of pexidartinib in the morning under fasting conditions
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
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 | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants |
| Age, Continuous | 36.6 years STANDARD_DEVIATION 8.06 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 24 | 0 / 24 |
| other Total, other adverse events | 1 / 24 | 0 / 24 | 2 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 24 |
Outcome results
Primary
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
Time frame: 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
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A | Area Under the Concentration-time Curve From Time of Dosing to Last Measurable Concentration (AUClast) and to Infinity (AUCinf) | AUClast | 64800 ng*hour/mL | Standard Deviation 19300 |
| Treatment A | Area Under the Concentration-time Curve From Time of Dosing to Last Measurable Concentration (AUClast) and to Infinity (AUCinf) | AUCinf | 66100 ng*hour/mL | Standard Deviation 19900 |
| Treatment B | Area Under the Concentration-time Curve From Time of Dosing to Last Measurable Concentration (AUClast) and to Infinity (AUCinf) | AUCinf | 104000 ng*hour/mL | Standard Deviation 27400 |
| Treatment B | Area Under the Concentration-time Curve From Time of Dosing to Last Measurable Concentration (AUClast) and to Infinity (AUCinf) | AUClast | 102000 ng*hour/mL | Standard Deviation 26300 |
| Treatment C | Area Under the Concentration-time Curve From Time of Dosing to Last Measurable Concentration (AUClast) and to Infinity (AUCinf) | AUClast | 53600 ng*hour/mL | Standard Deviation 14200 |
| Treatment C | Area Under the Concentration-time Curve From Time of Dosing to Last Measurable Concentration (AUClast) and to Infinity (AUCinf) | AUCinf | 54600 ng*hour/mL | Standard Deviation 15000 |
Primary
Maximum Observed Concentration in Plasma (Cmax) of Pexidartinib
Mean Cmax of pexidartinib is calculated for each treatment period
Time frame: 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
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Maximum Observed Concentration in Plasma (Cmax) of Pexidartinib | 4580 ng/mL | Standard Deviation 1240 |
| Treatment B | Maximum Observed Concentration in Plasma (Cmax) of Pexidartinib | 7090 ng/mL | Standard Deviation 1590 |
| Treatment C | Maximum Observed Concentration in Plasma (Cmax) of Pexidartinib | 3870 ng/mL | Standard Deviation 729 |
Primary
Terminal Half-life (t1/2)
Mean t1/2 for pexidartinib is calculated for each treatment period
Time frame: 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
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Terminal Half-life (t1/2) | 24.2 hours | Standard Deviation 5.28 |
| Treatment B | Terminal Half-life (t1/2) | 23.1 hours | Standard Deviation 4.68 |
| Treatment C | Terminal Half-life (t1/2) | 23.6 hours | Standard Deviation 5.04 |
Primary
Time to Cmax (Tmax)
Median Tmax of pexidartinib is calculated for each treatment period
Time frame: 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
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A | Time to Cmax (Tmax) | 2.00 hours |
| Treatment B | Time to Cmax (Tmax) | 3.50 hours |
| Treatment C | Time to Cmax (Tmax) | 3.30 hours |