A Study to Determine the Absolute Oral Bioavailability of Quizartinib Using a Radiolabeled Microtracer in Healthy Subjects
Condition: Healthy Subjects
Intervention: Quizartinib dihydrochloride; 14C-Quizartinib solution for infusion
Intervention description: Single oral dose of 60 mg quizartinib (2 x 30 mg tablets); 50 μg solution for infusion containing NMT 22.84 kBq 14C in 5 mL; administered once as a 15-minute infusion
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: Male
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Quizartinib; Healthy Subjects; Pharmacokinetics; Oral Bioavailability; Microtracer

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.
    

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).