Trial Outcomes & Findings for A Study of Quizartinib Pharmacokinetics in Participants With Moderate Hepatic Impairment (NCT NCT04473664)

NCT ID: NCT04473664

Last Updated: 2023-08-01

Results Overview

Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was an observed value for the study.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 12 participants
• Primary outcome timeframe: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose
• Results posted on: 2023-08-01

Participant Flow

A total of 12 participants who met all inclusion criteria and no exclusion criteria were enrolled from 22 Sep 2020 to 22 Jul 2021 at 3 clinics in the United States.

This study included a screening period up to 22 days prior to the enrolment and a 22 day in-clinic period, including screening.

Participant milestones

Measure	Participants With Moderate Hepatic Impairment Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.	Control Participants With Normal Hepatic Function Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1
Overall Study STARTED	6	6
Overall Study COMPLETED	6	6
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of Quizartinib Pharmacokinetics in Participants With Moderate Hepatic Impairment

Baseline characteristics by cohort

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.	Control Participants With Normal Hepatic Function n=6 Participants Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1	Total n=12 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	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Age, Continuous	57.0 years STANDARD_DEVIATION 6.78 • n=5 Participants	55.3 years STANDARD_DEVIATION 3.88 • n=7 Participants	56.2 years STANDARD_DEVIATION 5.34 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	6 Participants n=7 Participants	12 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	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	5 Participants n=7 Participants	11 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
Region of Enrollment United States	6 participants n=5 Participants	6 participants n=7 Participants	12 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib 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 an observed value for the study.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.	Control Participants With Normal Hepatic Function n=6 Participants Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1
Maximum Plasma Concentration (Cmax) of Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function	86.2 ng/mL Standard Deviation 15.8	90.7 ng/mL Standard Deviation 17.7

PRIMARY outcome

Timeframe: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose

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

Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was an observed value from the study.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.	Control Participants With Normal Hepatic Function n=6 Participants Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1
Time to Maximum Plasma Concentration (Tmax) for Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function	4.0 hours Interval 2.0 to 4.0	4.0 hours Interval 2.0 to 4.0

PRIMARY outcome

Timeframe: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib 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. 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. AUClast and AUCinf was assessed.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.	Control Participants With Normal Hepatic Function n=6 Participants Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1
Area Under the Plasma Concentration-Time Curve (AUC) for Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function AUClast	7480 ng*h/mL Standard Deviation 2930	7720 ng*h/mL Standard Deviation 4750
Area Under the Plasma Concentration-Time Curve (AUC) for Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function AUCinf	7880 ng*h/mL Standard Deviation 3540	8110 ng*h/mL Standard Deviation 5120

PRIMARY outcome

Timeframe: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose

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

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

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.	Control Participants With Normal Hepatic Function n=6 Participants Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1
Total Apparent Clearance (CL/F) for Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function	4.0 L/h Standard Deviation 1.9	5.0 L/h Standard Deviation 3.3

PRIMARY outcome

Timeframe: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose

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

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	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.	Control Participants With Normal Hepatic Function n=6 Participants Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1
Volume of Distribution in the Terminal Phase (Vz/F) for Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function	479 Liters Standard Deviation 121	577 Liters Standard Deviation 269

PRIMARY outcome

Timeframe: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib 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 noncompartmental analysis.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.	Control Participants With Normal Hepatic Function n=6 Participants Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1
Terminal Half-Life (t1/2) for Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function	93.7 hours Standard Deviation 36.0	96.3 hours Standard Deviation 34.7

SECONDARY outcome

Timeframe: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib 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 an observed value for the study.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.	Control Participants With Normal Hepatic Function n=6 Participants Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1
Maximum Plasma Concentration (Cmax) of Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function	17.3 ng/mL Standard Deviation 12.1	24.7 ng/mL Standard Deviation 18.2

SECONDARY outcome

Timeframe: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose

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

Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was an observed value from the study.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.	Control Participants With Normal Hepatic Function n=6 Participants Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1
Time to Maximum Plasma Concentration (Tmax) for Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function	7.00 hours Interval 4.0 to 48.0	7.00 hours Interval 4.0 to 72.0

SECONDARY outcome

Timeframe: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose

Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set. For AUCinf, 1 participant was excluded from the Moderate Hepatic Impairment group where AUCinf based on extrapolation was greater than 20% and 1 participant was excluded from the Normal Hepatic Function group where Adjusted r-squared value was greater than 0.9.

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. 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. AUClast and AUCinf was assessed.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.	Control Participants With Normal Hepatic Function n=6 Participants Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1
Area Under the Plasma Concentration-Time Curve (AUC) for Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function AUClast	2180 ng*h/mL Standard Deviation 1110	3240 ng*h/mL Standard Deviation 1280
Area Under the Plasma Concentration-Time Curve (AUC) for Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function AUCinf	2610 ng*h/mL Standard Deviation 878	3700 ng*h/mL Standard Deviation 1130

SECONDARY outcome

Timeframe: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib 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 noncompartmental analysis.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.	Control Participants With Normal Hepatic Function n=6 Participants Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1
Terminal Half-Life (t1/2) for Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function	111.1 hours Standard Deviation 48.7	81.4 hours Standard Deviation 20.7

SECONDARY outcome

Timeframe: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose

Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set. For AUCinf, 1 participant was excluded from the Moderate Hepatic Impairment group where AUCinf based on extrapolation was greater than 20% and 1 participant was excluded from the Normal Hepatic Function group where Adjusted r-squared value was greater than 0.9.

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 AC886 of AUCinf and AUClast are reported and were calculated using non-compartmental analysis. AUClast and AUCinf was assessed.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.	Control Participants With Normal Hepatic Function n=6 Participants Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1
Metabolite to Parent Ratio (MPR) Based on Area Under the Curve for Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function MPR AUClast	0.363 ratio Standard Deviation 0.269	0.653 ratio Standard Deviation 0.496
Metabolite to Parent Ratio (MPR) Based on Area Under the Curve for Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function MPR AUCinf	0.428 ratio Standard Deviation 0.261	0.762 ratio Standard Deviation 0.467

SECONDARY outcome

Timeframe: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib 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 an observed value for the study.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.	Control Participants With Normal Hepatic Function n=6 Participants Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1
Maximum Plasma Concentration (Cmax) of Unbound Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function	0.412 ng/mL Standard Deviation 0.320	0.881 ng/mL Standard Deviation 0.692

SECONDARY outcome

Timeframe: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib 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. 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. AUClast and AUCinf was assessed.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.	Control Participants With Normal Hepatic Function n=6 Participants Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1
Area Under the Plasma Concentration-Time Curve (AUC) of Unbound Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function Unbound Quizartinib AUClast	35.8 ng*h/mL Standard Deviation 30.4	84.5 ng*h/mL Standard Deviation 86.5
Area Under the Plasma Concentration-Time Curve (AUC) of Unbound Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function Unbound Quizartinib AUCinf	37.4 ng*h/mL Standard Deviation 31.3	88.4 ng*h/mL Standard Deviation 90.0

SECONDARY outcome

Timeframe: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose

Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set. Unbound AC886 concentration were below the level of quantification for 5 participants in the moderate hepatic impairment group and 2 participants in the normal hepatic function group.

Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was an observed value for the study.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=1 Participants Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.	Control Participants With Normal Hepatic Function n=4 Participants Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1
Maximum Plasma Concentration (Cmax) of Unbound Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function	0.0553 ng/mL Standard Deviation NA Not enough quantifiable data for estimation of standard deviation.	0.0658 ng/mL Standard Deviation 0.0490

SECONDARY outcome

Timeframe: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib 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. 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. AUClast and AUCinf was assessed.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.	Control Participants With Normal Hepatic Function n=6 Participants Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1
Area Under the Plasma Concentration-Time Curve (AUC) of Unbound Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function Unbound AC886 AUClast	4.06 ng*h/mL Standard Deviation NA 5 participants had concentration below level of detection so there was not enough quantifiable data for estimation of standard deviation.	7.17 ng*h/mL Standard Deviation 3.53
Area Under the Plasma Concentration-Time Curve (AUC) of Unbound Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function Unbound AC886 AUCinf	4.18 ng*h/mL Standard Deviation NA Not enough quantifiable data for estimation of standard deviation.	7.35 ng*h/mL Standard Deviation 3.56

SECONDARY outcome

Timeframe: Baseline up to 30 days after last dose, up to 2 months

Population: TEAEs were assessed using the Safety Analysis Set.

A Treatment-Emergent Adverse Events (TEAE) is defined as any event not present prior to the initiation of the drug treatment of the drug treatment or any event already present that worsens in either intensity or frequency following exposure to the drug treatment. Number of any TEAE that is related and unrelated to study medication is presented.

Outcome measures

Measure	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.	Control Participants With Normal Hepatic Function n=6 Participants Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1
Number of Participants With Treatment-emergent Adverse Events Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function	1 Participants	2 Participants

Adverse Events

Participants With Moderate Hepatic Impairment

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Control Participants With Normal Hepatic Function

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	Participants With Moderate Hepatic Impairment n=6 participants at risk Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.	Control Participants With Normal Hepatic Function n=6 participants at risk Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1
Gastrointestinal disorders Constipation	0.00% 0/6 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 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.	16.7% 1/6 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 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 Toothache	0.00% 0/6 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 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.	16.7% 1/6 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 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.
Infections and infestations Folliculitis	16.7% 1/6 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 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% 0/6 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 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.
Investigations Lipase increased	0.00% 0/6 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 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.	16.7% 1/6 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 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	0.00% 0/6 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 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.	16.7% 1/6 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 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 Sankyo, Inc.

Phone: 908-992-6400

Email: CTRinfo@dsi.com

Results disclosure agreements

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