This study has two parts. Part 1 will evaluate how pexidartinib affects the way the body processes CYP3A4 and CYP2C9 substrates using midazolam and tolbutamide, respectively, as probe agents. Part 2 will test the efficacy and safety of pexidartinib treatment in various tumor types. In Part 2, the same participants will continue to receive pexidartinib twice daily. Participants will be allowed to continue using pexidartinib as long as the participant derives benefit.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
32
Commercially available tolbutamide
Commercially available midazolam
Pexidartinib is formulated as opaque, white, 200-mg capsules
HonorHealth
Scottsdale, Arizona, United States
University of Arizona
Tucson, Arizona, United States
Stanford University
Palo Alto, California, United States
Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Midazolam
Plasma samples for midazolam were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 hours (h) (±10 minutes up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15).
Time frame: Baseline to 15 days post treatment
Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Tolbutamide
Plasma samples for tolbutamide were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 h (±10 min up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15).
Time frame: Baseline to 15 days post treatment
Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Midazolam
Plasma samples for midazolam were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 hours (h) (±10 minutes up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15).
Time frame: Baseline to 15 days post treatment
Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Tolbutamide
Plasma samples for tolbutamide were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 h (±10 min up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15).
Time frame: Baseline to 15 days post treatment
Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Midazolam
Plasma samples for midazolam were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 hours (h) (±10 minutes up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15).
Time frame: Baseline to 15 days post treatment
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University of Kansas Cancer Center
Westwood, Kansas, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Karmanos Cancer Center
Detroit, Michigan, United States
Northwell Health
Lake Success, New York, United States
Mary Crowley Cancer Research
Dallas, Texas, United States
Leids Universitair Medisch Centrum
Leiden, Netherlands
Christchurch Hospital NZ
Christchurch, New Zealand
...and 1 more locations
Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Tolbutamide
Plasma samples for tolbutamide were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 h (±10 min up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15).
Time frame: Baseline to 15 days post treatment
Overall Summary of Treatment-emergent Adverse Events
Adverse events that emerge during treatment, having been absent pre-treatment, or worsens relative to the pre-treatment state.
Time frame: Baseline to 1 year post treatment
Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Pexidartinib and ZAAD-1006a Metabolite
Plasma samples for pexidartinib and its metabolite were collected at predose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, and 10 (±1) h after the first dose on Day 3, and at steady state when co-administered with midazolam and tolbutamide on Day 13.
Time frame: Baseline to 13 days post treatment
Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Pexidartinib and ZAAD-1006a Metabolite
Plasma samples for pexidartinib and its metabolite were collected at predose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, and 10 (±1) h after the first dose on Day 3, and at steady state when co-administered with midazolam and tolbutamide on Day 13.
Time frame: Baseline to 13 days post treatment
Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Pexidartinib and ZAAD-1006a Metabolite
Plasma samples for pexidartinib and its metabolite were collected at predose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, and 10 (±1) h after the first dose on Day 3, and at steady state when co-administered with midazolam and tolbutamide on Day 13.
Time frame: Baseline to 13 days post treatment
Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Midazolam Metabolite, 1-Hydroxy Midazolam
Plasma samples for midazolam and 1-hydroxy midazolam were to be collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 (±10 min up to 8 h), 10 (±2), 24 (±2), and 48 (±2) hours on Days 1 to 3 and also when co-administered with pexidartinib on Days 3 to 5 and Days 13 to 15.
Time frame: Baseline to 13 days post treatment
Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Midazolam Metabolite, 1-Hydroxy Midazolam
Plasma samples for midazolam and 1-hydroxy midazolam were to be collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 (±10 min up to 8 h), 10 (±2), 24 (±2), and 48 (±2) hours on Days 1 to 3 and also when co-administered with pexidartinib on Days 3 to 5 and Days 13 to 15.
Time frame: Baseline to 13 days post treatment
Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Midazolam Metabolite, 1-Hydroxy Midazolam
Plasma samples for midazolam and 1-hydroxy midazolam were to be collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 (±10 min up to 8 h), 10 (±2), 24 (±2), and 48 (±2) hours on Days 1 to 3 and also when co-administered with pexidartinib on Days 3 to 5 and Days 13 to 15.
Time frame: Baseline to 13 days post treatment
Pharmacokinetic Analysis: Metabolite to Parent Ratio (MPR) for Midazolam
Plasma samples for midazolam were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 hours (h) (±10 minutes up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15). Plasma pharmacokinetic parameters calculated for Midazolam metabolite. 1-hydroxy midazolam and midazolam for the MPR value.
Time frame: Baseline to 13 days post treatment