A Study of the Effect of a Moderate CYP3A Inducer Efavirenz on Quizartinib Pharmacokinetics in Healthy Participants
Condition: Healthy Subjects; Drug-drug Interaction; Pharmacokinetics; Quizartinib
Intervention: Efavirenz; Quizartinib
Intervention description: Single oral dose, 600-mg tablet; Single oral dose, 60 mg (2 x 30 mg) tablets
Intervention MeSH terms: Efavirenz
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Healthy Subjects; Drug-drug Interaction; Pharmacokinetics; Quizartinib; CYP3A Inducer

Summary:

      This drug-drug interaction (DDI) study has been designed to investigate the effect of a
      moderate CYP3A inducer efavirenz on the pharmacokinetics of quizartinib and its major
      circulating active metabolite AC886.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female participants 18 to 55 years of age (inclusive), with a body mass index
             (BMI) of 18 kg/m^2 to 32 kg/m^2 (inclusive) and with a minimum body weight of 45 kg at
             Screening.

          -  In females, documented surgical sterilization, postmenopausal status for at least 1
             year (follicle stimulating hormone [FSH] > 40 mIU/mL serum at Screening), or agreement
             to use an approved form of contraception

          -  In males, agreement to avoid sperm donation for 6 months days after the dose of
             quizartinib

          -  Participants must agree to refrain from donation of blood from 56 days prior to
             Screening, plasma from 2 weeks prior to Screening, and platelets from 6 weeks prior to
             Screening.

          -  Liver function test results must be below the upper limit of normal. Hemoglobin levels
             must be ≥ 11.5 g/dL for female participants and ≥ 12.5 g/dL for male participants.

          -  All participants must be willing to refrain from consuming grapefruit/ grapefruit
             juice, Seville oranges, and pomegranates/pomegranate juice 10 days before the dose of
             the study drug is given on Day 1 until end-of-study.

        Exclusion Criteria:

          -  Any serious and/or unstable pre-existing medical, psychiatric disorder, or other
             conditions (including lab abnormality) that could interfere with participant's safety,
             obtaining informed consent or compliance to the study procedures.

          -  Laboratory results (serum chemistry, hematology, and urinalysis) outside the normal
             range, if considered clinically significant by the investigator. Estimated glomerular
             filtration rate (eGFR) < 90 mL/min at screening.

          -  Women who are pregnant or breastfeeding

          -  Use of any drugs or substances known to be inhibitors or inducers of CYP3A4/5 within
             28 days from the first dose or 5 half-lives, if known, of the drugs or substances,
             whichever is greater, prior to quizartinib administration and during the study.

          -  Receipt of any prescribed or over-the-counter (OTC) systemic, herbal (including St
             John's wort), or topical medication within 14 days of quizartinib administration, or
             any expectation of requiring use of such medication while participating in the study
             is prohibited.

          -  Presence or history of clinically severe adverse reaction to any drug

          -  History of stomach or intestinal surgery or resection that would potentially alter
             absorption and/or excretion of orally administered drugs (with the exception of
             appendectomy, hernia repair, and/or cholecystectomy)

          -  History of any cancer, except non-melanoma skin cancer, or resected nonmetastatic
             cancer with no evidence of disease accepted by the Investigator and Sponsor medical
             monitor

          -  A positive drugs of abuse screen from a urine ethanol test (unless the drug is
             medically prescribed by a licensed health care provider) or alcohol breath test at
             Screening or at Check-in on Day -1 or a participant who will not agree to smoke ≤10
             cigarettes or equivalent per day from Screening up to Enrollment, and is unable to be
             restricted to ≤5 cigarettes per day and for 6 hours post dose during their period of
             residence in the clinical unit

          -  Concomitant use of medications known to affect the elimination of serum creatinine
             (e.g., trimethoprim or cimetidine) and inhibitors of renal tubular secretion (eg,
             probenecid) within 14 days or 5 half-lives, if known, of the drugs, whichever is
             greater, prior to quizartinib administration

          -  History or presence of an abnormal electrocardiogram (ECG), which, in the
             investigator's opinion, is clinically significant and/or a QT interval corrected for
             heart rate using Fridericia's formula >450 milliseconds (ms) at Screening.

          -  Use of drugs with a risk of QT interval prolongation or torsade de pointes within 14
             days of Day -1 (or 5 drug half-lives, if 5 drug half-lives are expected to exceed 14
             days)

          -  Consumption of alcohol- and caffeine-containing beverages within 72 h prior to
             check-in and during confinement

          -  Positive serology for hepatitis B surface antigen (HBsAg) and HCV (healthy
             participants), hepatitis A virus (HAV) immunoglobulin M, or antihuman immunodeficiency
             virus (HIV) Type 1 and Type 2 (all subjects)

          -  Loss of more than 450 mL blood during the 3 months before the trial (eg, as a blood
             donor)

          -  Current enrollment in or have not yet completed at least 30 days or 5 elimination
             half-lives, whichever is longer, since receiving an investigational device or product,
             or receipt of other investigational agents within 30 days of quizartinib