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

NCT04796831 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: AC220-A-U1072021-000198-10
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Subjects

Keywords

Quizartinib; Healthy Subjects; Pharmacokinetics; Oral Bioavailability; Microtracer

Outcome Measures

Primary Outcomes (1)

• 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).

  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 (10)

• 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

• 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

• 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

• 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 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

Study Arms (1)

All Participants

EXPERIMENTAL

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; Drug: 14C-Quizartinib solution for infusion

Interventions

Quizartinib dihydrochloride DRUG

Single oral dose of 60 mg quizartinib (2 x 30 mg tablets)

Also known as: Quizartinib

All Participants

14C-Quizartinib solution for infusion DRUG

50 μg solution for infusion containing NMT 22.84 kBq 14C in 5 mL; administered once as a 15-minute infusion

All Participants

Eligibility Criteria

• Age: 18 Years - 55 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Daiichi Sankyo: lead
• Quotient Sciences: collaborator

Study Sites (1)

Quotient Sciences

Nottingham, NG11 6JS, United Kingdom

Location

MeSH Terms

Interventions

quizartinib

Results Point of Contact

• Title: Contact for Clinical Trial Information
• Organization: Daiichi Sankyo

CTRinfo@dsi.com

908-992-6400

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2021
• First Posted: March 15, 2021
• Study Start: April 26, 2021
• Primary Completion: June 11, 2021
• Study Completion: June 11, 2021
• Last Updated: January 11, 2023
• Results First Posted: January 11, 2023

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)