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

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ClinicalTrials.gov Identifier: NCT04223635
Recruitment Status : Completed
First Posted : January 10, 2020
Results First Posted : June 7, 2021
Last Update Posted : June 22, 2021
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Outcomes Assessor);   Primary Purpose: Treatment
Condition Moderate Hepatic Impairment
Intervention Drug: Pexidartinib
Enrollment 16
Recruitment Details 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.
Pre-assignment Details  
Arm/Group Title Normal HF Moderate HI
Hide Arm/Group Description 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. 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).
Period Title: Overall Study
Started 8 8
Completed 8 8
Not Completed 0 0
Arm/Group Title Normal HF Moderate HI Total
Hide Arm/Group Description 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. 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 of all reporting groups
Overall Number of Baseline Participants 8 8 16
Hide Baseline Analysis Population Description
Baseline characteristics were assessed using the Safety Analysis Set.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 8 participants 16 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
6
  75.0%
7
  87.5%
13
  81.3%
>=65 years
2
  25.0%
1
  12.5%
3
  18.8%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 8 participants 8 participants 16 participants
58.1  (6.69) 59.4  (4.34) 58.8  (5.48)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 8 participants 16 participants
Female
3
  37.5%
3
  37.5%
6
  37.5%
Male
5
  62.5%
5
  62.5%
10
  62.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 8 participants 16 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
  25.0%
1
  12.5%
3
  18.8%
White
6
  75.0%
7
  87.5%
13
  81.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilogram
Number Analyzed 8 participants 8 participants 16 participants
86.30  (13.49) 78.13  (14.83) 82.21  (14.33)
1.Primary Outcome
Title Maximum Plasma Concentration (Cmax) of Pexidartinib Following a Single Dose in Participants With Moderate Hepatic Impairment Compared to Healthy Participants
Hide Description Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was calculated using non-compartmental analysis.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.
Arm/Group Title Normal HF Moderate HI
Hide Arm/Group Description:
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.
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).
Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: ng/mL
1420  (738) 1250  (556)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Normal HF, Moderate HI
Comments [Not Specified]
Type of Statistical Test Other
Comments Least squares (LS) means were calculated from an analysis of variance (ANOVA) model on log-transformed scale. The LS means for each treatment were back transformed from the log scale to provide estimates of the geometric means (GMS). The ratio (%) of GMS was calculated and 90% Confidence Interval (CIs) for the ratio (%) of GMS were presented.
Method of Estimation Estimation Parameter Ratio (%) of Geometric LS Mean
Estimated Value 92.60
Confidence Interval (2-Sided) 90%
54.38 to 157.69
Estimation Comments For the comparison, moderate HI represents the numerator and normal HF represents the denominator.
2.Primary Outcome
Title Time of Maximum Plasma Concentration (Tmax) of Pexidartinib Following a Single Dose in Participants With Moderate Hepatic Impairment Compared to Healthy Participants
Hide Description Time of Maximum Plasma Concentration (Tmax) is defined as the time of maximum observed plasma concentration and was calculated using non-compartmental analysis.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.
Arm/Group Title Normal HF Moderate HI
Hide Arm/Group Description:
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.
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).
Overall Number of Participants Analyzed 8 8
Median (Full Range)
Unit of Measure: hours
1.9
(1.5 to 4.5)
2.5
(2.0 to 3.0)
3.Primary Outcome
Title 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
Hide Description 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.
Arm/Group Title Normal HF Moderate HI
Hide Arm/Group Description:
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.
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).
Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: ng•h/mL
26500  (12200) 38600  (16200)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Normal HF, Moderate HI
Comments [Not Specified]
Type of Statistical Test Other
Comments Least squares means were calculated from an analysis of variance (ANOVA) model on log-transformed scale. The LS means for each treatment were back transformed from the log scale to provide estimates of the geometric means (GMS). The ratio (%) of GMS was calculated and 90% CIs for the ratio (%) of GMS were presented.
Method of Estimation Estimation Parameter Ratio (%) of Geometric Least Square Mean
Estimated Value 147.17
Confidence Interval (2-Sided) 90%
95.39 to 227.07
Estimation Comments For the comparison, moderate HI represents the numerator and normal HF represents the denominator.
4.Primary Outcome
Title 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
Hide Description 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Normal HF Moderate HI
Hide Arm/Group Description:
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.
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).
Overall Number of Participants Analyzed 8 7
Mean (Standard Deviation)
Unit of Measure: ng•h/mL
27300  (12400) 38900  (17600)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Normal HF, Moderate HI
Comments [Not Specified]
Type of Statistical Test Other
Comments Least squares means were calculated from an analysis of variance (ANOVA) model on log-transformed scale. The LS means for each treatment were back transformed from the log scale to provide estimates of the geometric means (GMS). The ratio (%) of GMS was calculated and 90% CIs for the ratio (%) of GMS were presented.
Method of Estimation Estimation Parameter Ratio (%) of Geometric Least Square Mean
Estimated Value 142.87
Confidence Interval (2-Sided) 90%
91.21 to 223.79
Estimation Comments For the comparison, moderate HI represents the numerator and normal HF represents the denominator.
5.Primary Outcome
Title Elimination Rate Constant (Kel) of Pexidartinib Following a Single Dose in Participants With Moderate Hepatic Impairment Compared to Healthy Participants
Hide Description Elimination Rate Constant (Kel) is defined as elimination rate constant and was calculated using non-compartmental analysis.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
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..
Arm/Group Title Normal HF Moderate HI
Hide Arm/Group Description:
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.
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).
Overall Number of Participants Analyzed 8 7
Mean (Standard Deviation)
Unit of Measure: fraction per hour
0.02294  (0.002072) 0.019784  (0.0042775)
6.Primary Outcome
Title Terminal Elimination Half-Life (t1/2) of Pexidartinib Following a Single Dose in Participants With Moderate Hepatic Impairment Compared to Healthy Participants
Hide Description Terminal Elimination Half-Life (t1/2) is defined as terminal elimination half-life and was calculated using non-compartmental analysis.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Normal HF Moderate HI
Hide Arm/Group Description:
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.
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).
Overall Number of Participants Analyzed 8 7
Mean (Standard Deviation)
Unit of Measure: hours
30.4  (2.58) 36.5  (8.05)
7.Primary Outcome
Title Total Apparent Clearance (CL/F) of Pexidartinib Following a Single Dose in Participants With Moderate Hepatic Impairment Compared to Healthy Participants
Hide Description Total Apparent Clearance (CL/F) is defined as total apparent clearance and was calculated using non-compartmental analysis.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Normal HF Moderate HI
Hide Arm/Group Description:
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.
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).
Overall Number of Participants Analyzed 8 7
Mean (Standard Deviation)
Unit of Measure: liters per hour
9.046  (5.1294) 6.270  (3.2935)
8.Primary Outcome
Title Volume of Distribution in the Terminal Phase (Vz/F) Following a Single Dose in Participants With Moderate Hepatic Impairment Compared to Healthy Participants
Hide Description 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Normal HF Moderate HI
Hide Arm/Group Description:
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.
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).
Overall Number of Participants Analyzed 8 7
Mean (Standard Deviation)
Unit of Measure: liters
391.6  (205.29) 343.0  (238.12)
9.Secondary Outcome
Title Maximum Plasma Concentration (Cmax) of ZAAD-1006a Metabolite Following a Single Dose of Pexidartinib in Participants With Moderate Hepatic Impairment Compared to Healthy Participants
Hide Description Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was calculated using non-compartmental analysis.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.
Arm/Group Title Normal HF Moderate HI
Hide Arm/Group Description:
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.
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).
Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: ng/mL
1720  (950) 1250  (766)
10.Secondary Outcome
Title Maximum Plasma Concentration (Tmax) of ZAAD-1006a Metabolite Following a Single Dose of Pexidartinib in Participants With Moderate Hepatic Impairment Compared to Healthy Participants
Hide Description Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was calculated using non-compartmental analysis.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.
Arm/Group Title Normal HF Moderate HI
Hide Arm/Group Description:
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.
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).
Overall Number of Participants Analyzed 8 8
Mean (Full Range)
Unit of Measure: hours
3.0
(2.5 to 4.5)
10.0
(4.5 to 48.0)
11.Secondary Outcome
Title 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
Hide Description 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic parameters were assessed using the Pharmacokinetic Analysis Set.
Arm/Group Title Normal HF Moderate HI
Hide Arm/Group Description:
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.
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).
Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: ng•h/mL
AUCinf 43700  (29300) 78100  (38300)
AUClast 42700  (28800) 72700  (36900)
12.Secondary Outcome
Title 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
Hide Description Terminal Elimination Half-Life (t1/2) is defined as terminal elimination half-life and was calculated using non-compartmental analysis.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.
Arm/Group Title Normal HF Moderate HI
Hide Arm/Group Description:
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.
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).
Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: hours
28.9  (4.03) 37.9  (14.5)
13.Secondary Outcome
Title 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
Hide Description 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.
Arm/Group Title Normal HF Moderate HI
Hide Arm/Group Description:
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.
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).
Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: ratio
MPR AUCinf 1.08  (0.273) 1.27  (0.405)
MPR AUClast 1.09  (0.275) 1.30  (0.373)
14.Secondary Outcome
Title Percentage of Plasma Protein Binding of Pexidartinib and ZAAD-1006a Following a Single Dose in Participants With Moderate Hepatic Impairment Compared to Healthy Participants
Hide Description 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.
Time Frame 2.5 and 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Normal HF Moderate HI
Hide Arm/Group Description:
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.
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).
Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: percentage of protein binding
Pexidartinib at 2.5hrs post-dose Number Analyzed 7 participants 8 participants
99.9727  (0.00365) 99.9695  (0.00454)
Pexidartinib at 24hrs post-dose Number Analyzed 6 participants 8 participants
99.9703  (0.00765) 99.9664  (0.00815)
ZAAD-1006a at 2.5hrs post-dose Number Analyzed 8 participants 8 participants
99.8605  (0.01056) 99.8570  (0.03238)
ZAAD-1006a at 24hrs post-dose Number Analyzed 8 participants 8 participants
99.8631  (0.02055) 99.8534  (0.03868)
15.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Post-dose and up to 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
TEAEs were assessed using the Safety Analysis Set.
Arm/Group Title Normal HF Moderate HI
Hide Arm/Group Description:
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.
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).
Overall Number of Participants Analyzed 8 8
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAEs
1
  12.5%
2
  25.0%
Eye Disorders (Conjunctival haemorrhage)
0
   0.0%
1
  12.5%
Gastrointestinal Disorders (Dyspepsia)
0
   0.0%
1
  12.5%
Nervous System Disorders (Headache)
1
  12.5%
0
   0.0%
Time Frame 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 Event Reporting Description 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.
 
Arm/Group Title Normal HF Moderate HI
Hide Arm/Group Description 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. 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).
All-Cause Mortality
Normal HF Moderate HI
Affected / at Risk (%) Affected / at Risk (%)
Total   0/8 (0.00%)   0/8 (0.00%) 
Hide Serious Adverse Events
Normal HF Moderate HI
Affected / at Risk (%) Affected / at Risk (%)
Total   0/8 (0.00%)   0/8 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Normal HF Moderate HI
Affected / at Risk (%) Affected / at Risk (%)
Total   1/8 (12.50%)   2/8 (25.00%) 
Eye disorders     
Conjunctival haemorrhage  1  0/8 (0.00%)  1/8 (12.50%) 
Gastrointestinal disorders     
Gastrointestinal disorders  1  0/8 (0.00%)  1/8 (12.50%) 
Nervous system disorders     
Headache  1  1/8 (12.50%)  0/8 (0.00%) 
1
Term from vocabulary, MedDRA 23.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Contact for Clinical Trial Information
Organization: Daiichi Sanyko, Inc.
Phone: 908-992-6400
EMail: CTRinfo@dsi.com
Layout table for additonal information
Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT04223635    
Other Study ID Numbers: PL3397-A-U129
First Submitted: January 6, 2020
First Posted: January 10, 2020
Results First Submitted: May 11, 2021
Results First Posted: June 7, 2021
Last Update Posted: June 22, 2021