A Study to Determine the Absolute Oral Bioavailability of Quizartinib Using a Radiolabeled Microtracer in Healthy Subjects

• Sponsor: Daiichi Sankyo, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04796831
• Collaborator: (none)
• Enrollment: 8
• Location: 1
• Arm: 1
• Actual Duration (Months): 1.5
• Patients Per Site Per Month: 5.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Subjects	Drug: Quizartinib dihydrochloride; Drug: 14C-Quizartinib solution for infusion	Phase 1

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 and radiolabeled quizartinib, major circulating metabolites, and total radioactivity after a single oral dose and IV administration. Safety and tolerability of quizartinib will also be assessed.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Study to Determine the Absolute Oral Bioavailability of Quizartinib Using a Radiolabeled Microtracer in Healthy Subjects
• Actual Study Start Date: Apr 15, 2021
• Actual Primary Completion Date: May 31, 2021
• Actual Study Completion Date: May 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: All Participants Participants who will receive 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.	Drug: Quizartinib dihydrochloride; Single oral dose of 60 mg quizartinib (2 x 30 mg tablets); Other Names: Quizartinib ; Drug: 14C-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

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetic Parameters for Area Under the Serum Concentration-Time Curve for Quizartinib Following Intravenous and Oral Administrations of Quizartinib [Relative to oral dosing: Pre-dose, 1 hour, 2 hours, 4 hours, 4.25 hours, 4.5 hours, 4.75 hours, 5 hours, 6 hours, 8 hours, 12 hours, 24 hours, 48 hours, 72 hours, and 96 hours]

   Area under the serum concentration-time curve from the time of dosing to time Tlast (AUClast) and extrapolated to infinity (AUCinf) will be assessed.

Secondary Outcome Measures

1. Pharmacokinetic Parameters of Maximum (Peak) Observed Serum Concentration (Cmax) Following Intravenous and Oral Administrations of Quizartinib [Relative to oral dosing: Pre-dose (quizartinib+AC886 only), 1 hour (quizartinib+AC886 only), 2 hours (quizartinib+AC886 only), 4 hours, 4.25 hours, 4.5 hours, 4.75 hours, 5 hours, 6 hours, 8 hours, 12 hours, 24 hours, 48 hours, 72 hours, and 96 hours]

   Cmax will be assessed for Quizartinib, 14C-Quizartinib, AC886, and 14C-AC886.

2. Pharmacokinetic Parameters of Time to Maximum Serum Concentration (Tmax) Following Intravenous and Oral Administrations of Quizartinib [Relative to oral dosing: Pre-dose (quizartinib+AC886 only), 1 hour (quizartinib+AC886 only), 2 hours (quizartinib+AC886 only), 4 hours, 4.25 hours, 4.5 hours, 4.75 hours, 5 hours, 6 hours, 8 hours, 12 hours, 24 hours, 48 hours, 72 hours, and 96 hours]

   Tmax will be assessed for Quizartinib, 14C-Quizartinib, AC886, and 14C-AC886.

3. Pharmacokinetic Parameters of Terminal Half-Life (t1/2) Following Intravenous and Oral Administrations of Quizartinib [Relative to oral dosing: Pre-dose (quizartinib+AC886 only), 1 hour (quizartinib+AC886 only), 2 hours (quizartinib+AC886 only), 4 hours, 4.25 hours, 4.5 hours, 4.75 hours, 5 hours, 6 hours, 8 hours, 12 hours, 24 hours, 48 hours, 72 hours, and 96 hours]

   Half-life (t1/2) will be assessed for Quizartinib, 14C-Quizartinib, AC886, 14C-AC886, and total radioactivity.

4. Pharmacokinetic Parameters for Area Under the Serum Concentration-Time Curve (AUC) Following Intravenous and Oral Administrations of Quizartinib [Relative to oral dosing: Pre-dose (quizartinib+AC886 only), 1 hour (quizartinib+AC886 only), 2 hours (quizartinib+AC886 only), 4 hours, 4.25 hours, 4.5 hours, 4.75 hours, 5 hours, 6 hours, 8 hours, 12 hours, 24 hours, 48 hours, 72 hours, and 96 hours]

   AUC will be assessed for Quizartinib, 14C-Quizartinib, AC886, 14C-AC886, and total radioactivity.

5. Pharmacokinetic Parameters for Total Body Clearance (CL) Following Single-Dose Intravenous and Extravascular Administration Quizartinib [Relative to oral dosing: Pre-dose (quizartinib only), 1 hour (quizartinib only), 2 hours (quizartinib only), 4 hours, 4.25 hours, 4.5 hours, 4.75 hours, 5 hours, 6 hours, 8 hours, 12 hours, 24 hours, 48 hours, 72 hours, and 96 hours]

   Total body clearance (CL) and apparent total body clearance (CL/F) will be assessed following single-dose IV administration for 14C-quizartinib and single-dose extravascular administration for quizartinib, respectively.

6. Pharmacokinetic Parameters for Volume of Distribution (Vz) Following Following Single-Dose Intravenous and Extravascular Administration of Quizartinib Administration [Relative to oral dosing: Pre-dose (quizartinib only), 1 hour (quizartinib only), 2 hours (quizartinib only), 4 hours, 4.25 hours, 4.5 hours, 4.75 hours, 5 hours, 6 hours, 8 hours, 12 hours, 24 hours, 48 hours, 72 hours, and 96 hours]

   Volume of distribution based on the terminal phase (Vz) and apparent volume of distribution (Vz/F) will be assessed following single-dose IV administration for 14C-quizartinib and single-dose extravascular administration for quizartinib, respectively.

7. Pharmacokinetic Parameters 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 hours, 4.25 hours, 4.5 hours, 4.75 hours, 5 hours, 6 hours, 8 hours, 12 hours, 24 hours, 48 hours, 72 hours, and 96 hours]

   MPR will be assessed for AC886 and 14C-AC886.

8. Percentage of Participants With Treatment-emergent Adverse Events Following Intravenous and Oral Administrations of Quizartinib [Baseline up to approximately 6 weeks post-dose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: Male
• Accepts 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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Quotient Sciences	Nottingham		United Kingdom	NG11 6JS

Sponsors and Collaborators

• Daiichi Sankyo, Inc.

Investigators

• Study Director: Global Clinical Leader, Daiichi Sankyo, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Daiichi Sankyo, Inc.
• ClinicalTrials.gov Identifier: NCT04796831
• Other Study ID Numbers: AC220-A-U107; 2021-000198-10
• First Posted: Mar 15, 2021
• Last Update Posted: Sep 28, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Daiichi Sankyo, Inc.: Quizartinib; Healthy Subjects; Pharmacokinetics; Oral Bioavailability

Study Results

No Results Posted as of Sep 28, 2021