NCT04473664

A Study of Quizartinib Pharmacokinetics in Participants With Moderate Hepatic Impairment

Completed Phase 1 Results posted Last updated 1 August 2023

What this trial tests

Phase 1 trial testing Quizartinib in Hepatic Impairment in 12 participants. Completed in 22 July 2021.

Timeline

22 September 2020

Primary endpoint
22 July 2021

22 July 2021

Quick facts

Lead sponsor	Daiichi Sankyo
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	12
Start date	22 September 2020
Primary completion	22 July 2021
Estimated completion	22 July 2021
Sites	3 locations across United States

Drugs / interventions tested

• Quizartinib (QUIZARTINIB) — full drug profile →

Conditions studied

• Hepatic Impairment — all drugs for Hepatic Impairment →
• Moderate Impaired Hepatic Function — all drugs for Moderate Impaired Hepatic Function →

Sponsor

Daiichi Sankyo — full company profile →

Who can join

Adults 18 to 75, any sex, with Hepatic Impairment or Moderate Impaired Hepatic Function. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Maximum Plasma Concentration (Cmax) of Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function Primary · 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

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

Group	Value	95% CI
Participants With Moderate Hepatic Impairment	86.2	± 15.8
Control Participants With Normal Hepatic Function	90.7	± 17.7

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 Primary · 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

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

Group	Value	95% CI
Participants With Moderate Hepatic Impairment	4.0	2.0 – 4.0
Control Participants With Normal Hepatic Function	4.0	2.0 – 4.0

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 Primary · 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

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.

AUClast

Group	Value	95% CI
Participants With Moderate Hepatic Impairment	7480	± 2930
Control Participants With Normal Hepatic Function	7720	± 4750

AUCinf

Group	Value	95% CI
Participants With Moderate Hepatic Impairment	7880	± 3540
Control Participants With Normal Hepatic Function	8110	± 5120

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 Primary · 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

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

Group	Value	95% CI
Participants With Moderate Hepatic Impairment	4.0	± 1.9
Control Participants With Normal Hepatic Function	5.0	± 3.3

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 Primary · 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

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.

Group	Value	95% CI
Participants With Moderate Hepatic Impairment	479	± 121
Control Participants With Normal Hepatic Function	577	± 269

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 Primary · 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

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

Group	Value	95% CI
Participants With Moderate Hepatic Impairment	93.7	± 36.0
Control Participants With Normal Hepatic Function	96.3	± 34.7

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 Secondary · 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

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

Group	Value	95% CI
Participants With Moderate Hepatic Impairment	17.3	± 12.1
Control Participants With Normal Hepatic Function	24.7	± 18.2

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 Secondary · 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

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

Group	Value	95% CI
Participants With Moderate Hepatic Impairment	7.00	4.00 – 48.0
Control Participants With Normal Hepatic Function	7.00	4.00 – 72.0

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 Secondary · 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

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.

AUClast

Group	Value	95% CI
Participants With Moderate Hepatic Impairment	2180	± 1110
Control Participants With Normal Hepatic Function	3240	± 1280

AUCinf

Group	Value	95% CI
Participants With Moderate Hepatic Impairment	2610	± 878
Control Participants With Normal Hepatic Function	3700	± 1130

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 Secondary · 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

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

Group	Value	95% CI
Participants With Moderate Hepatic Impairment	111.1	± 48.7
Control Participants With Normal Hepatic Function	81.4	± 20.7

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 Secondary · 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

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.

MPR AUClast

Group	Value	95% CI
Participants With Moderate Hepatic Impairment	0.363	± 0.269
Control Participants With Normal Hepatic Function	0.653	± 0.496

MPR AUCinf

Group	Value	95% CI
Participants With Moderate Hepatic Impairment	0.428	± 0.261
Control Participants With Normal Hepatic Function	0.762	± 0.467

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 Secondary · 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

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

Group	Value	95% CI
Participants With Moderate Hepatic Impairment	0.412	± 0.320
Control Participants With Normal Hepatic Function	0.881	± 0.692

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Participants With Moderate Hepatic Impairment

Serious: 0/6 (0%)

Deaths: 0/6

Control Participants With Normal Hepatic Function

Serious: 0/6 (0%)

Deaths: 0/6

Other adverse events (5 terms — click to expand)

Reaction	System	Participants With Moderate…	Control Participants With …
Constipation	Gastrointestinal disorders	—	—
Toothache	Gastrointestinal disorders	—	—
Folliculitis	Infections and infestations	—	—
Lipase increased	Investigations	—	—
Headache	Nervous system disorders	—	—

Data from ClinicalTrials.gov NCT04473664 adverse events section.

Sponsor's own description

Quizartinib is a novel oral Class III receptor tyrosine kinase (RTK) inhibitor exhibiting highly potent and selective but reversible inhibition of Feline McDonough sarcoma (FMS)-like tyrosine kinase 3 (FLT3). Quizartinib is currently being studied alone or in combination with other agents as a treatment for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in adult and pediatric populations.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.