Status:

COMPLETED

A Study of the Effect of a Moderate CYP3A Inducer Efavirenz on Quizartinib Pharmacokinetics in Healthy Participants

Lead Sponsor:

Daiichi Sankyo Co., Ltd.

Conditions:

Healthy Subjects

Drug-drug Interaction

Eligibility:

All Genders

18-55 years

Phase:

PHASE1

Brief 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 metabol...

Detailed Description

In vitro, quizartinib is metabolized primarily by CYP3A. Therefore, co-administration of quizartinib with CYP3A inducers may decrease quizartinib exposure. This study will assess the effect of a moder...

Eligibility Criteria

Inclusion

  • 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

  • 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

Key Trial Info

Start Date :

August 19 2020

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

October 14 2020

Estimated Enrollment :

32 Patients enrolled

Trial Details

Trial ID

NCT04459598

Start Date

August 19 2020

End Date

October 14 2020

Last Update

June 28 2022

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San Antonio, Texas, United States, 78217