Clinical trial NCT04796831: A Study to Determine the Absolute Oral Bioavailability of Quizartinib Using a Radiolabeled Microtracer in Healthy Subjects
Official title: An Open Label Study to Determine the Absolute Oral Bioavailability of Quizartinib Using a Radiolabeled Microtracer in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: Quizartinib
Healthy Subjects
Pharmacokinetics
Oral Bioavailability
Microtracer
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: Quotient Sciences
First posted: 2021-03-15
Enrollment: 8
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: 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
timeFrame: 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
Secondary outcomes:
measure: Pharmacokinetic Parameter of Maximum (Peak) Observed Plasma Concentration (Cmax) Following Oral Administrations of Quizartinib
timeFrame: 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
measure: Pharmacokinetic Parameter of Maximum (Peak) Observed Plasma Concentration (Cmax) Following Intravenous Administrations of Quizartinib
timeFrame: 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
measure: Pharmacokinetic Parameter of Time to Maximum Plasma Concentration (Tmax) Following Intravenous and Oral Administrations of Quizartinib
timeFrame: 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
measure: Pharmacokinetic Parameter of Terminal Half-Life (t1/2) Following Intravenous and Oral Administrations of Quizartinib
timeFrame: 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
measure: Pharmacokinetic Parameter for Area Under the Plasma Concentration-Time Curve (AUC) Following Oral Administrations of Quizartinib
timeFrame: 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
measure: Pharmacokinetic Parameter for Area Under the Plasma Concentration-Time Curve (AUC) Following Intravenous Administrations of Quizartinib
timeFrame: 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
measure: Pharmacokinetic Parameter for Total Body Clearance (CL) Following Single-Dose Intravenous Administration of Quizartinib
timeFrame: 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
measure: Pharmacokinetic Parameter for Volume of Distribution (Vz) Following Following Single-Dose Intravenous Administration of Quizartinib
timeFrame: 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
measure: Pharmacokinetic Parameter of Metabolite to Parent Ratio (MPR) Based on Area Under the Curve Following Intravenous and Oral Administrations of Quizartinib
timeFrame: 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
measure: Number of Participants With Any Treatment-emergent Adverse Event Following Intravenous and Oral Administrations of Quizartinib
timeFrame: Baseline up to approximately 6 weeks post-dose
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Quotient Sciences
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: