Trial Outcomes & Findings for Study of Pexidartinib in Participants With Moderate Hepatic Impairment Compared With Healthy Participants (NCT NCT04223635)

NCT ID: NCT04223635

Last Updated: 2021-06-22

Results Overview

Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf ) is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity and was calculated using non-compartmental analysis.

• Recruitment status: COMPLETED
• Study phase: EARLY_PHASE1
• Target enrollment: 16 participants
• Primary outcome timeframe: Pre-dose (within 60 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose
• Results posted on: 2021-06-22

Participant Flow

A total of 16 participants who met all inclusion criteria and no exclusion criteria were enrolled from 07 Jan 2020 to 02 Oct 2020 at 2 clinics in the United States.

Participant milestones

Measure	Normal HF Healthy matched participants with normal hepatic function (HF) who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10 hours(h) before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration.	Moderate HI Participants with moderate HI who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10 hours(h) before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration. Moderate hepatic impairment (HI) was assessed by National Cancer Institute - Organ Dysfunction Working Group (NCI-ODWG).
Overall Study STARTED	8	8
Overall Study COMPLETED	8	8
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Pexidartinib in Participants With Moderate Hepatic Impairment Compared With Healthy Participants

Baseline characteristics by cohort

Measure	Normal HF n=8 Participants Healthy matched participants with normal HF who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration.	Moderate HI n=8 Participants Participants with moderate HI who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration. Moderate hepatic impairment (HI) was assessed by National Cancer Institute - Organ Dysfunction Working Group (NCI-ODWG).	Total n=16 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Age, Continuous	58.1 years STANDARD_DEVIATION 6.69 • n=5 Participants	59.4 years STANDARD_DEVIATION 4.34 • n=7 Participants	58.8 years STANDARD_DEVIATION 5.48 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Weight	86.30 kilogram STANDARD_DEVIATION 13.49 • n=5 Participants	78.13 kilogram STANDARD_DEVIATION 14.83 • n=7 Participants	82.21 kilogram STANDARD_DEVIATION 14.33 • n=5 Participants

PRIMARY outcome

Timeframe: Pre-dose (within 60 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose

Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.

Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was calculated using non-compartmental analysis.

Outcome measures

Measure	Normal HF n=8 Participants Healthy matched participants with normal HF who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration.	Moderate HI n=8 Participants Participants with moderate HI who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration. Moderate hepatic impairment (HI) was assessed by National Cancer Institute - Organ Dysfunction Working Group (NCI-ODWG).
Maximum Plasma Concentration (Cmax) of Pexidartinib Following a Single Dose in Participants With Moderate Hepatic Impairment Compared to Healthy Participants	1420 ng/mL Standard Deviation 738	1250 ng/mL Standard Deviation 556

PRIMARY outcome

Timeframe: Pre-dose (within 60 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose

Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.

Time of Maximum Plasma Concentration (Tmax) is defined as the time of maximum observed plasma concentration and was calculated using non-compartmental analysis.

Outcome measures

Measure	Normal HF n=8 Participants Healthy matched participants with normal HF who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration.	Moderate HI n=8 Participants Participants with moderate HI who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration. Moderate hepatic impairment (HI) was assessed by National Cancer Institute - Organ Dysfunction Working Group (NCI-ODWG).
Time of Maximum Plasma Concentration (Tmax) of Pexidartinib Following a Single Dose in Participants With Moderate Hepatic Impairment Compared to Healthy Participants	1.9 hours Interval 1.5 to 4.5	2.5 hours Interval 2.0 to 3.0

PRIMARY outcome

Timeframe: Pre-dose (within 60 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose

Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.

Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method and was calculated using non-compartmental analysis.

Outcome measures

Measure	Normal HF n=8 Participants Healthy matched participants with normal HF who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration.	Moderate HI n=8 Participants Participants with moderate HI who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration. Moderate hepatic impairment (HI) was assessed by National Cancer Institute - Organ Dysfunction Working Group (NCI-ODWG).
Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) of Pexidartinib Following a Single Dose in Participants With Moderate Hepatic Impairment Compared to Healthy Participants	26500 ng•h/mL Standard Deviation 12200	38600 ng•h/mL Standard Deviation 16200

PRIMARY outcome

Timeframe: Pre-dose (within 60 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose

Population: The pharmacokinetic parameter of Area Under the Plasma Concentration-Time Curve up to Infinity was assessed using the Pharmacokinetic Analysis Set except for 1 participant that did not meet the protocol inclusion criteria for this analysis.

Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf ) is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity and was calculated using non-compartmental analysis.

Outcome measures

Measure	Normal HF n=8 Participants Healthy matched participants with normal HF who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration.	Moderate HI n=7 Participants Participants with moderate HI who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration. Moderate hepatic impairment (HI) was assessed by National Cancer Institute - Organ Dysfunction Working Group (NCI-ODWG).
Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf ) of Pexidartinib Following a Single Dose in Participants With Moderate Hepatic Impairment Compared to Healthy Participants	27300 ng•h/mL Standard Deviation 12400	38900 ng•h/mL Standard Deviation 17600

PRIMARY outcome

Timeframe: Pre-dose (within 60 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose

Population: The pharmacokinetic parameter of Elimination Rate Constant was assessed using the Pharmacokinetic Analysis Set except for 1 participant that did not meet the protocol inclusion criteria for this analysis..

Elimination Rate Constant (Kel) is defined as elimination rate constant and was calculated using non-compartmental analysis.

Outcome measures

Measure	Normal HF n=8 Participants Healthy matched participants with normal HF who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration.	Moderate HI n=7 Participants Participants with moderate HI who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration. Moderate hepatic impairment (HI) was assessed by National Cancer Institute - Organ Dysfunction Working Group (NCI-ODWG).
Elimination Rate Constant (Kel) of Pexidartinib Following a Single Dose in Participants With Moderate Hepatic Impairment Compared to Healthy Participants	0.02294 fraction per hour Standard Deviation 0.002072	0.019784 fraction per hour Standard Deviation 0.0042775

PRIMARY outcome

Timeframe: Pre-dose (within 60 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose

Population: The pharmacokinetic parameter of Terminal Elimination Half-Life was assessed using the Pharmacokinetic Analysis Set except for 1 participant that did not meet the protocol inclusion criteria for this analysis.

Terminal Elimination Half-Life (t1/2) is defined as terminal elimination half-life and was calculated using non-compartmental analysis.

Outcome measures

Measure	Normal HF n=8 Participants Healthy matched participants with normal HF who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration.	Moderate HI n=7 Participants Participants with moderate HI who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration. Moderate hepatic impairment (HI) was assessed by National Cancer Institute - Organ Dysfunction Working Group (NCI-ODWG).
Terminal Elimination Half-Life (t1/2) of Pexidartinib Following a Single Dose in Participants With Moderate Hepatic Impairment Compared to Healthy Participants	30.4 hours Standard Deviation 2.58	36.5 hours Standard Deviation 8.05

PRIMARY outcome

Timeframe: Pre-dose (within 60 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose

Population: The pharmacokinetic parameter of Total Apparent Clearance was assessed using the Pharmacokinetic Analysis Set except for 1 participant that did not meet the protocol inclusion criteria for this analysis.

Total Apparent Clearance (CL/F) is defined as total apparent clearance and was calculated using non-compartmental analysis.

Outcome measures

Measure	Normal HF n=8 Participants Healthy matched participants with normal HF who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration.	Moderate HI n=7 Participants Participants with moderate HI who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration. Moderate hepatic impairment (HI) was assessed by National Cancer Institute - Organ Dysfunction Working Group (NCI-ODWG).
Total Apparent Clearance (CL/F) of Pexidartinib Following a Single Dose in Participants With Moderate Hepatic Impairment Compared to Healthy Participants	9.046 liters per hour Standard Deviation 5.1294	6.270 liters per hour Standard Deviation 3.2935

PRIMARY outcome

Timeframe: Pre-dose (within 60 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose

Population: The pharmacokinetic parameter of Volume of Distribution in the Terminal Phase was assessed using the Pharmacokinetic Analysis Set except for 1 participant that did not meet the protocol inclusion criteria for this analysis.

Volume of Distribution in the Terminal Phase (Vz/F) is defined as volume of distribution in the terminal phase and was calculated using non-compartmental analysis.

Outcome measures

Measure	Normal HF n=8 Participants Healthy matched participants with normal HF who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration.	Moderate HI n=7 Participants Participants with moderate HI who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration. Moderate hepatic impairment (HI) was assessed by National Cancer Institute - Organ Dysfunction Working Group (NCI-ODWG).
Volume of Distribution in the Terminal Phase (Vz/F) Following a Single Dose in Participants With Moderate Hepatic Impairment Compared to Healthy Participants	391.6 liters Standard Deviation 205.29	343.0 liters Standard Deviation 238.12

SECONDARY outcome

Timeframe: Pre-dose (within 60 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose

Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.

Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was calculated using non-compartmental analysis.

Outcome measures

Measure	Normal HF n=8 Participants Healthy matched participants with normal HF who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration.	Moderate HI n=8 Participants Participants with moderate HI who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration. Moderate hepatic impairment (HI) was assessed by National Cancer Institute - Organ Dysfunction Working Group (NCI-ODWG).
Maximum Plasma Concentration (Cmax) of ZAAD-1006a Metabolite Following a Single Dose of Pexidartinib in Participants With Moderate Hepatic Impairment Compared to Healthy Participants	1720 ng/mL Standard Deviation 950	1250 ng/mL Standard Deviation 766

SECONDARY outcome

Timeframe: Pre-dose (within 60 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose

Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.

Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was calculated using non-compartmental analysis.

Outcome measures

Measure	Normal HF n=8 Participants Healthy matched participants with normal HF who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration.	Moderate HI n=8 Participants Participants with moderate HI who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration. Moderate hepatic impairment (HI) was assessed by National Cancer Institute - Organ Dysfunction Working Group (NCI-ODWG).
Maximum Plasma Concentration (Tmax) of ZAAD-1006a Metabolite Following a Single Dose of Pexidartinib in Participants With Moderate Hepatic Impairment Compared to Healthy Participants	3.0 hours Interval 2.5 to 4.5	10.0 hours Interval 4.5 to 48.0

SECONDARY outcome

Timeframe: Pre-dose (within 60 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose

Population: Pharmacokinetic parameters were assessed using the Pharmacokinetic Analysis Set.

Area Under the Concentration-Time Curve (AUCinf) is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity and AUClast is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method. AUCinf and AUClast are reported and were calculated using non-compartmental analysis.

Outcome measures

Measure	Normal HF n=8 Participants Healthy matched participants with normal HF who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration.	Moderate HI n=8 Participants Participants with moderate HI who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration. Moderate hepatic impairment (HI) was assessed by National Cancer Institute - Organ Dysfunction Working Group (NCI-ODWG).
Area Under the Concentration-Time Curve (AUCinf) of of ZAAD-1006a Metabolite Following a Single Dose of Pexidartinib in Participants With Moderate Hepatic Impairment Compared to Healthy Participants AUCinf	43700 ng•h/mL Standard Deviation 29300	78100 ng•h/mL Standard Deviation 38300
Area Under the Concentration-Time Curve (AUCinf) of of ZAAD-1006a Metabolite Following a Single Dose of Pexidartinib in Participants With Moderate Hepatic Impairment Compared to Healthy Participants AUClast	42700 ng•h/mL Standard Deviation 28800	72700 ng•h/mL Standard Deviation 36900

SECONDARY outcome

Timeframe: Pre-dose (within 60 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose

Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.

Terminal Elimination Half-Life (t1/2) is defined as terminal elimination half-life and was calculated using non-compartmental analysis.

Outcome measures

Measure	Normal HF n=8 Participants Healthy matched participants with normal HF who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration.	Moderate HI n=8 Participants Participants with moderate HI who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration. Moderate hepatic impairment (HI) was assessed by National Cancer Institute - Organ Dysfunction Working Group (NCI-ODWG).
Terminal Elimination Half-Life (t1/2) of ZAAD-1006a Metabolite Following a Single Dose of Pexidartinib in Subjects Participants With Moderate Hepatic Impairment Compared to Healthy Participants	28.9 hours Standard Deviation 4.03	37.9 hours Standard Deviation 14.5

SECONDARY outcome

Timeframe: Pre-dose (within 60 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose

Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.

AUCinf is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity and AUClast is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method. MPR is defined as a metabolite to parent ratio with metabolite as the numerator and the parent as the denominator. MPR corrected for molecular weight of ZAAD-1006a of AUCinf and AUClast are reported and were calculated using non-compartmental analysis.

Outcome measures

Measure	Normal HF n=8 Participants Healthy matched participants with normal HF who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration.	Moderate HI n=8 Participants Participants with moderate HI who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration. Moderate hepatic impairment (HI) was assessed by National Cancer Institute - Organ Dysfunction Working Group (NCI-ODWG).
Metabolite-to-Parent Ratio (MPR) Corrected for Molecular Weight of ZAAD-1006a Metabolite Following a Single Dose of Pexidartinib in Participants With Moderate Hepatic Impairment Compared to Healthy Participants MPR AUCinf	1.08 ratio Standard Deviation 0.273	1.27 ratio Standard Deviation 0.405
Metabolite-to-Parent Ratio (MPR) Corrected for Molecular Weight of ZAAD-1006a Metabolite Following a Single Dose of Pexidartinib in Participants With Moderate Hepatic Impairment Compared to Healthy Participants MPR AUClast	1.09 ratio Standard Deviation 0.275	1.30 ratio Standard Deviation 0.373

SECONDARY outcome

Timeframe: 2.5 and 24 hours post-dose

Population: The pharmacokinetic parameter of Percentage of Plasma Protein Binding was assessed using the Pharmacokinetic Analysis Set. Only those participants with data available at the specified timepoints were analyzed.

Protein binding (percentage bound) was determined in all participants at 2.5h and 24h post-dose. Plasma was harvested and analyzed for the quantification of pexidartinib using a validated liquid chromatography-tandem mass spectrometry method and the ZAAD-1006a metabolite was analyzed using a qualified liquid chromatography-tandem mass spectrometry assay.

Outcome measures

Measure	Normal HF n=8 Participants Healthy matched participants with normal HF who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration.	Moderate HI n=8 Participants Participants with moderate HI who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration. Moderate hepatic impairment (HI) was assessed by National Cancer Institute - Organ Dysfunction Working Group (NCI-ODWG).
Percentage of Plasma Protein Binding of Pexidartinib and ZAAD-1006a Following a Single Dose in Participants With Moderate Hepatic Impairment Compared to Healthy Participants Pexidartinib at 2.5hrs post-dose	99.9727 percentage of protein binding Standard Deviation 0.00365	99.9695 percentage of protein binding Standard Deviation 0.00454
Percentage of Plasma Protein Binding of Pexidartinib and ZAAD-1006a Following a Single Dose in Participants With Moderate Hepatic Impairment Compared to Healthy Participants Pexidartinib at 24hrs post-dose	99.9703 percentage of protein binding Standard Deviation 0.00765	99.9664 percentage of protein binding Standard Deviation 0.00815
Percentage of Plasma Protein Binding of Pexidartinib and ZAAD-1006a Following a Single Dose in Participants With Moderate Hepatic Impairment Compared to Healthy Participants ZAAD-1006a at 2.5hrs post-dose	99.8605 percentage of protein binding Standard Deviation 0.01056	99.8570 percentage of protein binding Standard Deviation 0.03238
Percentage of Plasma Protein Binding of Pexidartinib and ZAAD-1006a Following a Single Dose in Participants With Moderate Hepatic Impairment Compared to Healthy Participants ZAAD-1006a at 24hrs post-dose	99.8631 percentage of protein binding Standard Deviation 0.02055	99.8534 percentage of protein binding Standard Deviation 0.03868

SECONDARY outcome

Timeframe: Post-dose and up to 30 days

Population: TEAEs were assessed using the Safety Analysis Set.

A Treatment-Emergent Adverse Event (TEAE) is defined as any event not present prior to the initiation of the drug treatment or any event already present that worsens in either intensity or frequency following exposure to the drug treatment.

Outcome measures

Measure	Normal HF n=8 Participants Healthy matched participants with normal HF who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration.	Moderate HI n=8 Participants Participants with moderate HI who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration. Moderate hepatic impairment (HI) was assessed by National Cancer Institute - Organ Dysfunction Working Group (NCI-ODWG).
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAE) by System Organ Class and Preferred Term Following a Single Dose of Pexidartinib in Participants With Moderate Hepatic Impairment Compared to Healthy Participants Eye Disorders (Conjunctival haemorrhage)	0 Participants	1 Participants
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAE) by System Organ Class and Preferred Term Following a Single Dose of Pexidartinib in Participants With Moderate Hepatic Impairment Compared to Healthy Participants Gastrointestinal Disorders (Dyspepsia)	0 Participants	1 Participants
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAE) by System Organ Class and Preferred Term Following a Single Dose of Pexidartinib in Participants With Moderate Hepatic Impairment Compared to Healthy Participants Nervous System Disorders (Headache)	1 Participants	0 Participants
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAE) by System Organ Class and Preferred Term Following a Single Dose of Pexidartinib in Participants With Moderate Hepatic Impairment Compared to Healthy Participants Any TEAEs	1 Participants	2 Participants

Adverse Events

Normal HF

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Moderate HI

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Normal HF n=8 participants at risk Healthy matched participants with normal HF who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration.	Moderate HI n=8 participants at risk Participants with moderate HI who received 200mg pexidartinib on Day 1 with 240 mL water. Participants fasted for at least 10h before pexidartinib dosing and continued to fast for at least 4h after pexidartinib administration. Moderate hepatic impairment (HI) was assessed by National Cancer Institute - Organ Dysfunction Working Group (NCI-ODWG).
Eye disorders Conjunctival haemorrhage	0.00% 0/8 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 10 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	12.5% 1/8 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 10 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Gastrointestinal disorders Gastrointestinal disorders	0.00% 0/8 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 10 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	12.5% 1/8 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 10 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Nervous system disorders Headache	12.5% 1/8 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 10 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	0.00% 0/8 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 10 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.

Additional Information

Contact for Clinical Trial Information

Daiichi Sanyko, Inc.

Phone: 908-992-6400

Email: CTRinfo@dsi.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place