Healthy Subjects
Conditions
Keywords
Quizartinib, Healthy Subjects, Pharmacokinetics, Oral Bioavailability, Microtracer
Brief summary
Quizartinib, a selective FLT3 inhibitor, is being developed as a treatment for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The absolute oral bioavailability of quizartinib has not yet been studied. This study is designed to estimate quizartinib bioavailability of quizartinib following oral and intravenous (IV) administration.
Detailed description
Quizartinib bioavailability based on the dose-adjusted exposure of quizartinib following oral and IV administration will be assessed in healthy male subjects. The primary objective of this study is to determine the absolute oral bioavailability of quizartinib. Secondary objectives will include characterizing the plasma PK of quizartinib, radiolabeled quizartinib, and the major circulating metabolite after a single oral dose and IV administration. Safety and tolerability of quizartinib will also be assessed.
Interventions
Single oral dose of 60 mg quizartinib (2 x 30 mg tablets)
DRUG14C-Quizartinib solution for infusion
50 μg solution for infusion containing NMT 22.84 kBq 14C in 5 mL; administered once as a 15-minute infusion
Sponsors
Quotient Sciences
Daiichi Sankyo
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy males aged 18 years to 55 years of age (inclusive) at the time of signing informed consent * Body mass index (BMI) of 18.0 kg/m\^2 to 32.0 kg/m\^2 (inclusive) at screening
Exclusion criteria
* History or presence of: * Clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal (GI), endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease, as judged by the Investigator. * Any other condition, including laboratory abnormality, that in the opinion of the Investigator, would jeopardize the safety of the subject, obtaining informed consent, compliance to the study procedures, or the validity of the study results. * History of a clinically significant illness, in the opinion of the Investigator, within 4 weeks prior to administration of quizartinib. * History, or presence in the average of triplicate ECGs at screening and admission (Day -1), of any of the following cardiac conduction abnormalities: * QT interval corrected with Fridericia's formula (QTcF) \> 450 milliseconds (ms). * Evidence of second- or third-degree atrioventricular block. * Evidence of complete left or right bundle branch block. * QRS or T wave morphology that could, in the Investigator's opinion, render QT interval assessment unreliable (confirmed with triplicate ECG). * Laboratory results (serum chemistry, hematology, coagulation, and urinalysis) outside the normal range, if considered clinically significant by the Investigator at screening or admission (Day -1). * Estimated creatinine clearance (CrCl) \<90 mL/min (calculated using Cockcroft-Gault Equation) at screening. * Use of drugs with a risk of QT interval prolongation or Torsades de Pointes (TdP) within 14 days of admission (Day -1) (or 5 drug half-lives, if 5 drug half-lives are expected to exceed 14 days).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Absolute Oral Bioavailability for Quizartinib As Assessed By Pharmacokinetic Parameters for Area Under the Plasma Concentration-Time Curve Following Intravenous and Oral Administrations of Quizartinib | Relative to oral dosing: Pre-dose and at 1, 2, 4, 4.25, 4.5, 4.75, 5, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480, and 504 hours | The absolute bioavailability assessment for quizartinib was based on the pharmacokinetic parameters area under the curve (AUC) from the time of dosing to time Tlast (AUClast) and AUC from the time of dosing extrapolated to infinity (AUCinf) for quizartinib following intravenous and oral administrations. Pharmacokinetic parameters were calculated using a non-compartmental approach. PK parameters were computed using Phoenix™ WinNonlin® (Version 8.0). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Parameter of Maximum (Peak) Observed Plasma Concentration (Cmax) Following Intravenous Administrations of Quizartinib | Relative to oral dosing: 4, 4.25, 4.5, 4.75, 5, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480, and 504 hours | Maximum (peak) plasma concentration (Cmax) was an observed value from the study. Cmax was assessed for 14C-Quizartinib and 14C-AC886. |
| Pharmacokinetic Parameter of Time to Maximum Plasma Concentration (Tmax) Following Intravenous and Oral Administrations of Quizartinib | Relative to oral dosing: Pre-dose, 1, 2, 4, 4.25, 4.5, 4.75, 5, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480, and 504 hours | Time to maximum plasma concentration (Tmax) was an observed value from the study. Tmax was assessed for Quizartinib and AC886. |
| Pharmacokinetic Parameter of Terminal Half-Life (t1/2) Following Intravenous and Oral Administrations of Quizartinib | Relative to oral dosing: Pre-dose, 1, 2, 4, 4.25, 4.5, 4.75, 5, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480, and 504 hours | Pharmacokinetic parameters were calculated using a non-compartmental approach. PK parameters were computed using Phoenix™ WinNonlin® (Version 8.0). Half-life (t1/2) was assessed for Quizartinib, 14C-Quizartinib, AC886, 14C-AC886. |
| Pharmacokinetic Parameter for Area Under the Plasma Concentration-Time Curve (AUC) Following Oral Administrations of Quizartinib | Relative to oral dosing: Pre-dose, 1, 2, 4, 4.25, 4.5, 4.75, 5, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480, and 504 hours | Pharmacokinetic parameters were calculated using a non-compartmental approach. PK parameters were computed using Phoenix™ WinNonlin® (Version 8.0). Area under the concentration-time curve from the time of dosing to time (AUClast) and area under the concentration-time curve from the time of dosing extrapolated to infinity (AUCinf) were assessed for Quizartinib and AC886. |
| Pharmacokinetic Parameter of Maximum (Peak) Observed Plasma Concentration (Cmax) Following Oral Administrations of Quizartinib | Relative to oral dosing: Pre-dose, 1, 2, 4, 4.25, 4.5, 4.75, 5, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480, and 504 hours | Maximum (peak) plasma concentration (Cmax) was an observed value from the study. Cmax was assessed for Quizartinib and active metabolite AC886. |
| Pharmacokinetic Parameter for Total Body Clearance (CL) Following Single-Dose Intravenous Administration of Quizartinib | Relative to oral dosing: 4, 4.25, 4.5, 4.75, 5, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480, and 504 hours | Pharmacokinetic parameters were calculated using a non-compartmental approach. PK parameters were computed using Phoenix™ WinNonlin® (Version 8.0). Total body clearance (CL) was assessed following single-dose IV administration for 14C-quizartinib. |
| Pharmacokinetic Parameter for Volume of Distribution (Vz) Following Following Single-Dose Intravenous Administration of Quizartinib | Relative to oral dosing: 4, 4.25, 4.5, 4.75, 5, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480, and 504 hours | Pharmacokinetic parameters were calculated using a non-compartmental approach. PK parameters were computed using Phoenix™ WinNonlin® (Version 8.0). Volume of distribution based on the terminal phase (Vz) was assessed following single-dose IV administration for 14C-quizartinib. |
| Pharmacokinetic Parameter of Metabolite to Parent Ratio (MPR) Based on Area Under the Curve Following Intravenous and Oral Administrations of Quizartinib | Relative to oral dosing: Pre-dose (AC886 only), 1 hour (AC886 only), 2 hours (AC886 only), 4, 4.25, 4.5, 4.75, 5, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480, and 504 hours | Pharmacokinetic parameters were calculated using a non-compartmental approach. PK parameters were computed using Phoenix™ WinNonlin® (Version 8.0). MPR was assessed for AC886 and 14C-AC886. |
| Number of Participants With Any Treatment-emergent Adverse Event Following Intravenous and Oral Administrations of Quizartinib | Baseline up to approximately 6 weeks post-dose | Treatment-emergent adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) version 24.0. |
| Pharmacokinetic Parameter for Area Under the Plasma Concentration-Time Curve (AUC) Following Intravenous Administrations of Quizartinib | Relative to oral dosing: 4, 4.25, 4.5, 4.75, 5, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480, and 504 hours | Pharmacokinetic parameters were calculated using a non-compartmental approach. PK parameters were computed using Phoenix™ WinNonlin® (Version 8.0). Area under the concentration-time curve from the time of dosing to time (AUClast) and area under the concentration-time curve from the time of dosing extrapolated to infinity (AUCinf) were assessed for 14C-Quizartinib and 14C-AC886. |
Countries
United Kingdom
Participant flow
Recruitment details
A total of 8 participants who met all inclusion criteria and no exclusion criteria were included in this study and were enrolled at 1 clinic center in the United Kingdom.
Pre-assignment details
Participants underwent preliminary screening procedures up to 21 days before investigational medicinal product (IMP) administration (Day -21 to Day-2). Participants were admitted in the morning on the day prior to IMP administration (i.e., Day -1), at which time admission procedures were undertaken to confirm eligibility. Participants were dosed in the morning of Day 1 following an overnight fast of a minimum of 8 hours for the oral dose (a minimum of 12 hours for the intravenous dose).
Participants by arm
| Arm | Count |
|---|---|
| All Participants Participants who received a single, oral dose of 60 mg quizartinib and a single, IV administration of 50 μg 14C-quizartinib solution for infusion at 4 hours post-oral dosing. | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age, Continuous | 35.1 years STANDARD_DEVIATION 9.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United Kingdom | 8 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 1 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Percentage of Absolute Oral Bioavailability for Quizartinib As Assessed By Pharmacokinetic Parameters for Area Under the Plasma Concentration-Time Curve Following Intravenous and Oral Administrations of Quizartinib
The absolute bioavailability assessment for quizartinib was based on the pharmacokinetic parameters area under the curve (AUC) from the time of dosing to time Tlast (AUClast) and AUC from the time of dosing extrapolated to infinity (AUCinf) for quizartinib following intravenous and oral administrations. Pharmacokinetic parameters were calculated using a non-compartmental approach. PK parameters were computed using Phoenix™ WinNonlin® (Version 8.0).
Time frame: Relative to oral dosing: Pre-dose and at 1, 2, 4, 4.25, 4.5, 4.75, 5, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480, and 504 hours
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Evaluable Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Percentage of Absolute Oral Bioavailability for Quizartinib As Assessed By Pharmacokinetic Parameters for Area Under the Plasma Concentration-Time Curve Following Intravenous and Oral Administrations of Quizartinib | Area under the concentration-time curve from the time of dosing to time Tlast (AUClast) | 72.12 percentage of oral bioavailability | Standard Deviation 7.18 |
| All Participants | Percentage of Absolute Oral Bioavailability for Quizartinib As Assessed By Pharmacokinetic Parameters for Area Under the Plasma Concentration-Time Curve Following Intravenous and Oral Administrations of Quizartinib | Area under the concentration-time curve from the time of dosing extrapolated to infinity (AUCinf) | 71.47 percentage of oral bioavailability | Standard Deviation 7.34 |
Secondary
Number of Participants With Any Treatment-emergent Adverse Event Following Intravenous and Oral Administrations of Quizartinib
Treatment-emergent adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) version 24.0.
Time frame: Baseline up to approximately 6 weeks post-dose
Population: Treatment-emergent adverse events were assessed in the Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Participants | Number of Participants With Any Treatment-emergent Adverse Event Following Intravenous and Oral Administrations of Quizartinib | 1 Participants |
Secondary
Pharmacokinetic Parameter for Area Under the Plasma Concentration-Time Curve (AUC) Following Intravenous Administrations of Quizartinib
Pharmacokinetic parameters were calculated using a non-compartmental approach. PK parameters were computed using Phoenix™ WinNonlin® (Version 8.0). Area under the concentration-time curve from the time of dosing to time (AUClast) and area under the concentration-time curve from the time of dosing extrapolated to infinity (AUCinf) were assessed for 14C-Quizartinib and 14C-AC886.
Time frame: Relative to oral dosing: 4, 4.25, 4.5, 4.75, 5, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480, and 504 hours
Population: Pharmacokinetic parameters were assessed in patients with available data in the Pharmacokinetic Evaluable Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Pharmacokinetic Parameter for Area Under the Plasma Concentration-Time Curve (AUC) Following Intravenous Administrations of Quizartinib | Intravenous: 14C-Quizartinib, AUClast | 18800 pg*h/mL | Standard Deviation 4950 |
| All Participants | Pharmacokinetic Parameter for Area Under the Plasma Concentration-Time Curve (AUC) Following Intravenous Administrations of Quizartinib | Intravenous: 14C-AC886, AUClast | 5170 pg*h/mL | Standard Deviation 1330 |
| All Participants | Pharmacokinetic Parameter for Area Under the Plasma Concentration-Time Curve (AUC) Following Intravenous Administrations of Quizartinib | Intravenous: 14C-Quizartinib, AUCinf | 19600 pg*h/mL | Standard Deviation 5390 |
| All Participants | Pharmacokinetic Parameter for Area Under the Plasma Concentration-Time Curve (AUC) Following Intravenous Administrations of Quizartinib | Intravenous: 14C-AC886, AUCinf | 5620 pg*h/mL | Standard Deviation 1270 |
Secondary
Pharmacokinetic Parameter for Area Under the Plasma Concentration-Time Curve (AUC) Following Oral Administrations of Quizartinib
Pharmacokinetic parameters were calculated using a non-compartmental approach. PK parameters were computed using Phoenix™ WinNonlin® (Version 8.0). Area under the concentration-time curve from the time of dosing to time (AUClast) and area under the concentration-time curve from the time of dosing extrapolated to infinity (AUCinf) were assessed for Quizartinib and AC886.
Time frame: Relative to oral dosing: Pre-dose, 1, 2, 4, 4.25, 4.5, 4.75, 5, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480, and 504 hours
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Evaluable Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Pharmacokinetic Parameter for Area Under the Plasma Concentration-Time Curve (AUC) Following Oral Administrations of Quizartinib | Oral (plasma): AC886, AUCinf | 5580 ng*h/mL | Standard Deviation 1200 |
| All Participants | Pharmacokinetic Parameter for Area Under the Plasma Concentration-Time Curve (AUC) Following Oral Administrations of Quizartinib | Oral (plasma): Quizartinib, AUClast | 17000 ng*h/mL | Standard Deviation 4990 |
| All Participants | Pharmacokinetic Parameter for Area Under the Plasma Concentration-Time Curve (AUC) Following Oral Administrations of Quizartinib | Oral (plasma): AC886, AUClast | 5300 ng*h/mL | Standard Deviation 1310 |
| All Participants | Pharmacokinetic Parameter for Area Under the Plasma Concentration-Time Curve (AUC) Following Oral Administrations of Quizartinib | Oral (plasma): Quizartinib, AUCinf | 17600 ng*h/mL | Standard Deviation 5500 |
Secondary
Pharmacokinetic Parameter for Total Body Clearance (CL) Following Single-Dose Intravenous Administration of Quizartinib
Pharmacokinetic parameters were calculated using a non-compartmental approach. PK parameters were computed using Phoenix™ WinNonlin® (Version 8.0). Total body clearance (CL) was assessed following single-dose IV administration for 14C-quizartinib.
Time frame: Relative to oral dosing: 4, 4.25, 4.5, 4.75, 5, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480, and 504 hours
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Evaluable Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Pharmacokinetic Parameter for Total Body Clearance (CL) Following Single-Dose Intravenous Administration of Quizartinib | 2.31 L/h | Standard Deviation 0.624 |
Secondary
Pharmacokinetic Parameter for Volume of Distribution (Vz) Following Following Single-Dose Intravenous Administration of Quizartinib
Pharmacokinetic parameters were calculated using a non-compartmental approach. PK parameters were computed using Phoenix™ WinNonlin® (Version 8.0). Volume of distribution based on the terminal phase (Vz) was assessed following single-dose IV administration for 14C-quizartinib.
Time frame: Relative to oral dosing: 4, 4.25, 4.5, 4.75, 5, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480, and 504 hours
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Evaluable Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Pharmacokinetic Parameter for Volume of Distribution (Vz) Following Following Single-Dose Intravenous Administration of Quizartinib | 318 Liters | Standard Deviation 142 |
Secondary
Pharmacokinetic Parameter of Maximum (Peak) Observed Plasma Concentration (Cmax) Following Intravenous Administrations of Quizartinib
Maximum (peak) plasma concentration (Cmax) was an observed value from the study. Cmax was assessed for 14C-Quizartinib and 14C-AC886.
Time frame: Relative to oral dosing: 4, 4.25, 4.5, 4.75, 5, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480, and 504 hours
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Evaluable Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Pharmacokinetic Parameter of Maximum (Peak) Observed Plasma Concentration (Cmax) Following Intravenous Administrations of Quizartinib | 14C-Quizartinib | 1030 pg/mL | Standard Deviation 317 |
| All Participants | Pharmacokinetic Parameter of Maximum (Peak) Observed Plasma Concentration (Cmax) Following Intravenous Administrations of Quizartinib | 14C-AC886 | 31.9 pg/mL | Standard Deviation 11.4 |
Secondary
Pharmacokinetic Parameter of Maximum (Peak) Observed Plasma Concentration (Cmax) Following Oral Administrations of Quizartinib
Maximum (peak) plasma concentration (Cmax) was an observed value from the study. Cmax was assessed for Quizartinib and active metabolite AC886.
Time frame: Relative to oral dosing: Pre-dose, 1, 2, 4, 4.25, 4.5, 4.75, 5, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480, and 504 hours
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Evaluable Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Pharmacokinetic Parameter of Maximum (Peak) Observed Plasma Concentration (Cmax) Following Oral Administrations of Quizartinib | Oral (plasma): Quizartinib | 209 ng/mL | Standard Deviation 33.4 |
| All Participants | Pharmacokinetic Parameter of Maximum (Peak) Observed Plasma Concentration (Cmax) Following Oral Administrations of Quizartinib | Oral (plasma): AC886 | 40.7 ng/mL | Standard Deviation 24 |
Secondary
Pharmacokinetic Parameter of Metabolite to Parent Ratio (MPR) Based on Area Under the Curve Following Intravenous and Oral Administrations of Quizartinib
Pharmacokinetic parameters were calculated using a non-compartmental approach. PK parameters were computed using Phoenix™ WinNonlin® (Version 8.0). MPR was assessed for AC886 and 14C-AC886.
Time frame: Relative to oral dosing: Pre-dose (AC886 only), 1 hour (AC886 only), 2 hours (AC886 only), 4, 4.25, 4.5, 4.75, 5, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480, and 504 hours
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Evaluable Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Pharmacokinetic Parameter of Metabolite to Parent Ratio (MPR) Based on Area Under the Curve Following Intravenous and Oral Administrations of Quizartinib | Oral (plasma): MPR(AUClast), AC886 | 0.35 metabolite-to-parent ratio | Standard Deviation 0.164 |
| All Participants | Pharmacokinetic Parameter of Metabolite to Parent Ratio (MPR) Based on Area Under the Curve Following Intravenous and Oral Administrations of Quizartinib | Oral (plasma): MPR(AUCinf), AC886 | 0.35 metabolite-to-parent ratio | Standard Deviation 0.158 |
| All Participants | Pharmacokinetic Parameter of Metabolite to Parent Ratio (MPR) Based on Area Under the Curve Following Intravenous and Oral Administrations of Quizartinib | Intravenous: MPR(AUClast), 14C-AC886 | 0.29 metabolite-to-parent ratio | Standard Deviation 0.098 |
| All Participants | Pharmacokinetic Parameter of Metabolite to Parent Ratio (MPR) Based on Area Under the Curve Following Intravenous and Oral Administrations of Quizartinib | Intravenous: MPR(AUCinf), 14C-AC886 | 0.30 metabolite-to-parent ratio | Standard Deviation 0.093 |
Secondary
Pharmacokinetic Parameter of Terminal Half-Life (t1/2) Following Intravenous and Oral Administrations of Quizartinib
Pharmacokinetic parameters were calculated using a non-compartmental approach. PK parameters were computed using Phoenix™ WinNonlin® (Version 8.0). Half-life (t1/2) was assessed for Quizartinib, 14C-Quizartinib, AC886, 14C-AC886.
Time frame: Relative to oral dosing: Pre-dose, 1, 2, 4, 4.25, 4.5, 4.75, 5, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480, and 504 hours
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Evaluable Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Pharmacokinetic Parameter of Terminal Half-Life (t1/2) Following Intravenous and Oral Administrations of Quizartinib | Oral (plasma): Quizartinib | 94.2 hours | Standard Deviation 23.7 |
| All Participants | Pharmacokinetic Parameter of Terminal Half-Life (t1/2) Following Intravenous and Oral Administrations of Quizartinib | Oral (plasma): AC886 | 111 hours | Standard Deviation 45.4 |
| All Participants | Pharmacokinetic Parameter of Terminal Half-Life (t1/2) Following Intravenous and Oral Administrations of Quizartinib | Intravenous: Quizartinib | 95.7 hours | Standard Deviation 29.7 |
| All Participants | Pharmacokinetic Parameter of Terminal Half-Life (t1/2) Following Intravenous and Oral Administrations of Quizartinib | Intravenous: AC886 | 90.4 hours | Standard Deviation 31.2 |
Secondary
Pharmacokinetic Parameter of Time to Maximum Plasma Concentration (Tmax) Following Intravenous and Oral Administrations of Quizartinib
Time to maximum plasma concentration (Tmax) was an observed value from the study. Tmax was assessed for Quizartinib and AC886.
Time frame: Relative to oral dosing: Pre-dose, 1, 2, 4, 4.25, 4.5, 4.75, 5, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480, and 504 hours
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Evaluable Population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| All Participants | Pharmacokinetic Parameter of Time to Maximum Plasma Concentration (Tmax) Following Intravenous and Oral Administrations of Quizartinib | Oral (plasma): Quizartinib | 4.75 hours |
| All Participants | Pharmacokinetic Parameter of Time to Maximum Plasma Concentration (Tmax) Following Intravenous and Oral Administrations of Quizartinib | Oral (plasma): AC886 | 5.51 hours |
| All Participants | Pharmacokinetic Parameter of Time to Maximum Plasma Concentration (Tmax) Following Intravenous and Oral Administrations of Quizartinib | Intravenous: Quizartinib | 0.25 hours |
| All Participants | Pharmacokinetic Parameter of Time to Maximum Plasma Concentration (Tmax) Following Intravenous and Oral Administrations of Quizartinib | Intravenous: AC886 | 44.02 hours |