Trial Outcomes & Findings for Effect of Pexidartinib on the Way the Body Processes CYP3A4 and CYP2C9 Substrates (Pharmacokinetics) (NCT NCT03291288)

NCT ID: NCT03291288

Last Updated: 2021-05-14

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

32 participants

Primary outcome timeframe

Baseline to 15 days post treatment

Results posted on

2021-05-14

Participant Flow

A total of 32 participants who met all inclusion and no exclusion criteria were enrolled in the study; 2 participants did not receive pexidartinib treatment.

This open-label, single sequence crossover study comprised of 2 parts. Part 1 was the initial single sequence crossover part to evaluate the effect of pexidartinib on the pharmacokinetics of midazolam and tolbutamide, the drug-drug interaction (DDI) phase. Part 2 was an evaluation of efficacy and safety of pexidartinib treatment in various tumors.

Participant milestones

Participant milestones
Measure	Part 1: Drug-drug Interaction Phase On Day 1, participants received the single oral dose of midazolam (2 mg) and tolbutamide (500 mg). On Day 3, pexidartinib (800 mg/day) administered as 400 mg twice daily (BID) was initiated and continued throughout the remainder of Part 1 and into Part 2. On the first day of pexidartinib treatment (Day 3), a single dose of midazolam (2 mg) and tolbutamide (500 mg) was co-administered with the morning pexidartinib dose (400 mg). On Day 13, a single dose of midazolam (2 mg) and tolbutamide (500 mg) was co-administered with the morning dose of pexidartinib (400 mg).	Part 2: Pexidartinib Only All participants received pexidartinib twice daily (BID) dosing in 28-day cycles at the 400 mg/day dose for up to one year.
Drug-drug Interaction Phase STARTED	32	0
Drug-drug Interaction Phase COMPLETED	26	0
Drug-drug Interaction Phase NOT COMPLETED	6	0
Pexidartinib Only STARTED	0	26
Pexidartinib Only COMPLETED	0	24
Pexidartinib Only NOT COMPLETED	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1: Drug-drug Interaction Phase On Day 1, participants received the single oral dose of midazolam (2 mg) and tolbutamide (500 mg). On Day 3, pexidartinib (800 mg/day) administered as 400 mg twice daily (BID) was initiated and continued throughout the remainder of Part 1 and into Part 2. On the first day of pexidartinib treatment (Day 3), a single dose of midazolam (2 mg) and tolbutamide (500 mg) was co-administered with the morning pexidartinib dose (400 mg). On Day 13, a single dose of midazolam (2 mg) and tolbutamide (500 mg) was co-administered with the morning dose of pexidartinib (400 mg).	Part 2: Pexidartinib Only All participants received pexidartinib twice daily (BID) dosing in 28-day cycles at the 400 mg/day dose for up to one year.
Drug-drug Interaction Phase Adverse Event	2	0
Drug-drug Interaction Phase Disease progression	1	0
Drug-drug Interaction Phase Other	3	0
Pexidartinib Only Ongoing	0	2

Baseline Characteristics

Effect of Pexidartinib on the Way the Body Processes CYP3A4 and CYP2C9 Substrates (Pharmacokinetics)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=30 Participants All participants who received pexidartinib in Part 1 and Part 2 of the study.
Age, Categorical <=18 years	2 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	19 Participants n=5 Participants
Age, Categorical >=65 years	9 Participants n=5 Participants
Age, Continuous	50.8 years STANDARD_DEVIATION 19.3 • n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	23 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 15 days post treatment

Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Evaluable population.

Outcome measures

Outcome measures
Measure	Part 1: Midazolam Only n=32 Participants All participants received a single oral dose of midazolam (2 mg) on Day 1.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1) n=30 Participants All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11) n=25 Participants All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.
Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Midazolam	13.6 ng/mL Standard Deviation 6.8	12.0 ng/mL Standard Deviation 4.9	9.7 ng/mL Standard Deviation 4.1

PRIMARY outcome

Timeframe: Baseline to 15 days post treatment

Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Evaluable population.

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).

Outcome measures

Outcome measures
Measure	Part 1: Midazolam Only n=32 Participants All participants received a single oral dose of midazolam (2 mg) on Day 1.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1) n=30 Participants All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11) n=25 Participants All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.
Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Tolbutamide	44400 ng/mL Standard Deviation 13100	46700 ng/mL Standard Deviation 16300	44400 ng/mL Standard Deviation 12200

PRIMARY outcome

Timeframe: Baseline to 15 days post treatment

Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Evaluable population.

Outcome measures

Outcome measures
Measure	Part 1: Midazolam Only n=32 Participants All participants received a single oral dose of midazolam (2 mg) on Day 1.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1) n=30 Participants All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11) n=25 Participants All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.
Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Midazolam	0.525 hours Interval 0.333 to 1.37	0.5 hours Interval 0.417 to 1.42	0.5 hours Interval 0.333 to 0.917

PRIMARY outcome

Timeframe: Baseline to 15 days post treatment

Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Evaluable population.

Outcome measures

Outcome measures
Measure	Part 1: Midazolam Only n=32 Participants All participants received a single oral dose of midazolam (2 mg) on Day 1.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1) n=30 Participants All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11) n=25 Participants All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.
Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Tolbutamide	2.90 hours Interval 1.0 to 8.2	2.94 hours Interval 1.52 to 8.08	3.17 hours Interval 2.45 to 6.02

PRIMARY outcome

Timeframe: Baseline to 15 days post treatment

Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Evaluable population.

Outcome measures

Outcome measures
Measure	Part 1: Midazolam Only n=32 Participants All participants received a single oral dose of midazolam (2 mg) on Day 1.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1) n=30 Participants All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11) n=25 Participants All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.
Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Midazolam	43.7 ng*hour/mL Standard Deviation 34.1	31.6 ng*hour/mL Standard Deviation 19.6	18.5 ng*hour/mL Standard Deviation 8.2

PRIMARY outcome

Timeframe: Baseline to 15 days post treatment

Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Evaluable population.

Outcome measures

Outcome measures
Measure	Part 1: Midazolam Only n=32 Participants All participants received a single oral dose of midazolam (2 mg) on Day 1.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1) n=30 Participants All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11) n=25 Participants All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.
Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Tolbutamide	500000 ng*hour/mL Standard Deviation 196000	585000 ng*hour/mL Standard Deviation 234000	700000 ng*hour/mL Standard Deviation 207000

PRIMARY outcome

Timeframe: Baseline to 1 year post treatment

Population: Treatment-emergent adverse events (TEAEs) were assessed in the Safety Analysis population.

Adverse events that emerge during treatment, having been absent pre-treatment, or worsens relative to the pre-treatment state.

Outcome measures

Outcome measures
Measure	Part 1: Midazolam Only n=30 Participants All participants received a single oral dose of midazolam (2 mg) on Day 1.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1) n=25 Participants All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11) All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.
Overall Summary of Treatment-emergent Adverse Events TEAEs	24 Participants	23 Participants	—
Overall Summary of Treatment-emergent Adverse Events Pexidartinib-related TEAEs	16 Participants	20 Participants	—
Overall Summary of Treatment-emergent Adverse Events Treatment-emergent serious adverse events (SAEs)	5 Participants	5 Participants	—
Overall Summary of Treatment-emergent Adverse Events Pexidartinib-related SAEs	1 Participants	1 Participants	—

SECONDARY outcome

Timeframe: Baseline to 13 days post treatment

Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Evaluable population.

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.

Outcome measures

Outcome measures
Measure	Part 1: Midazolam Only n=30 Participants All participants received a single oral dose of midazolam (2 mg) on Day 1.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1) n=25 Participants All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11) All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.
Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Pexidartinib and ZAAD-1006a Metabolite Pexidartinib	3140 ng/mL Standard Deviation 1250	8320 ng/mL Standard Deviation 2530	—
Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Pexidartinib and ZAAD-1006a Metabolite ZAAD-1006a	3330 ng/mL Standard Deviation 1520	13500 ng/mL Standard Deviation 5980	—

SECONDARY outcome

Timeframe: Baseline to 13 days post treatment

Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Evaluable population.

Outcome measures

Outcome measures
Measure	Part 1: Midazolam Only n=30 Participants All participants received a single oral dose of midazolam (2 mg) on Day 1.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1) n=25 Participants All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11) All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.
Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Pexidartinib and ZAAD-1006a Metabolite Pexidartinib	2.03 hours Interval 1.08 to 7.83	1.93 hours Interval 0.92 to 8.03	—
Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Pexidartinib and ZAAD-1006a Metabolite ZAAD-1006a	6.04 hours Interval 2.37 to 9.07	2.53 hours Interval 0.0 to 8.25	—

SECONDARY outcome

Timeframe: Baseline to 13 days post treatment

Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Evaluable population.

Outcome measures

Outcome measures
Measure	Part 1: Midazolam Only n=30 Participants All participants received a single oral dose of midazolam (2 mg) on Day 1.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1) n=25 Participants All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11) All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.
Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Pexidartinib and ZAAD-1006a Metabolite ZAAD-1006a	18300 ng*hour/mL Standard Deviation 7240	102000 ng*hour/mL Standard Deviation 44100	—
Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Pexidartinib and ZAAD-1006a Metabolite Pexidartinib	14400 ng*hour/mL Standard Deviation 5870	53200 ng*hour/mL Standard Deviation 17800	—

SECONDARY outcome

Timeframe: Baseline to 13 days post treatment

Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Evaluable population.

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.

Outcome measures

Outcome measures
Measure	Part 1: Midazolam Only n=32 Participants All participants received a single oral dose of midazolam (2 mg) on Day 1.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1) n=30 Participants All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11) n=25 Participants All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.
Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Midazolam Metabolite, 1-Hydroxy Midazolam	49.7 ng/mL Standard Deviation 17.9	52.1 ng/mL Standard Deviation 17.4	55.7 ng/mL Standard Deviation 17.4

SECONDARY outcome

Timeframe: Baseline to 13 days post treatment

Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Evaluable population.

Outcome measures

Outcome measures
Measure	Part 1: Midazolam Only n=32 Participants All participants received a single oral dose of midazolam (2 mg) on Day 1.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1) n=30 Participants All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11) n=25 Participants All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.
Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Midazolam Metabolite, 1-Hydroxy Midazolam	1.0 hours Interval 0.333 to 1.45	0.933 hours Interval 0.417 to 1.37	0.833 hours Interval 0.383 to 1.55

SECONDARY outcome

Timeframe: Baseline to 13 days post treatment

Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Evaluable population.

Outcome measures

Outcome measures
Measure	Part 1: Midazolam Only n=32 Participants All participants received a single oral dose of midazolam (2 mg) on Day 1.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1) n=30 Participants All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11) n=25 Participants All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.
Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Midazolam Metabolite, 1-Hydroxy Midazolam	200 ng*hour/mL Standard Deviation 93	206 ng*hour/mL Standard Deviation 95.5	212 ng*hour/mL Standard Deviation 99.6

SECONDARY outcome

Timeframe: Baseline to 13 days post treatment

Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Evaluable population.

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.

Outcome measures

Outcome measures
Measure	Part 1: Midazolam Only n=32 Participants All participants received a single oral dose of midazolam (2 mg) on Day 1.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1) n=30 Participants All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.	Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11) n=25 Participants All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.
Pharmacokinetic Analysis: Metabolite to Parent Ratio (MPR) for Midazolam	587 Ratio Standard Deviation 359	750 Ratio Standard Deviation 391	1220 Ratio Standard Deviation 657

Adverse Events

Part 1: Drug-drug Interaction Phase

Serious events: 5 serious events

Other events: 24 other events

Deaths: 1 deaths

Part 2: Pexidartinib Only

Serious events: 5 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part 1: Drug-drug Interaction Phase n=30 participants at risk On Day 1, participants received the single oral dose of midazolam (2 mg) and tolbutamide (500 mg). On Day 3, pexidartinib (800 mg/day) administered as 400 mg twice daily (BID) was initiated and continued throughout the remainder of Part 1 and into Part 2. On the first day of pexidartinib treatment (Day 3), a single dose of midazolam (2 mg) and tolbutamide (500 mg) was co-administered with the morning pexidartinib dose (400 mg). On Day 13, a single dose of midazolam (2 mg) and tolbutamide (500 mg) was co-administered with the morning dose of pexidartinib (400 mg).	Part 2: Pexidartinib Only n=25 participants at risk All participants received pexidartinib twice daily (BID) dosing in 28-day cycles at the 400 mg/day dose for up to one year.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	0.00% 0/30 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.	4.0% 1/25 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.
Cardiac disorders Pericardial effusion	0.00% 0/30 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.	4.0% 1/25 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.
Cardiac disorders Cardiac tamponade	0.00% 0/30 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.	4.0% 1/25 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.
Gastrointestinal disorders Malignant bowel obstruction	3.3% 1/30 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.	0.00% 0/25 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.
Gastrointestinal disorders Dysphagia	3.3% 1/30 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.	0.00% 0/25 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.
Gastrointestinal disorders Oesophagitis	0.00% 0/30 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.	4.0% 1/25 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.
Gastrointestinal disorders Large intestinal obstruction	3.3% 1/30 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.	0.00% 0/25 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/30 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.	4.0% 1/25 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.
Hepatobiliary disorders Cholestasis	0.00% 0/30 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.	4.0% 1/25 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.
Immune system disorders Hypersensitivity	3.3% 1/30 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.	0.00% 0/25 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.
Immune system disorders Pneumonia	0.00% 0/30 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.	4.0% 1/25 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/30 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.	4.0% 1/25 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.
Musculoskeletal and connective tissue disorders Chest wall haematoma	0.00% 0/30 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.	4.0% 1/25 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	3.3% 1/30 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.	0.00% 0/25 • Adverse events were collected after first dose up to 28 days after the last dose of study drug, up to 1 year. A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.

Other adverse events

Additional Information

Contact for Clinical Trial Information

Daiichi Sankyo, Inc.

Phone: 908-992-6400

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place