Phase 1
Completed N=32
A Study of the Effect of a Moderate CYP3A Inducer Efavirenz on Quizartinib Pharmacokinetics in Healthy Participants
Healthy Subjects · Drug-drug Interaction · Pharmacokinetics · Quizartinib
Source: ClinicalTrials.gov NCT04459598 ↗
Enrolled (actual)
32
Serious AEs
0.0%
Results posted
Jun 2022
Primary outcomePrimary: Maximum Plasma Concentration (Cmax) Following Single Dose of Quizartinib With or Without Efavirenz — 130.0; 238.0; 11.0; 34.4 ng/mL
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Plasma Concentration (Cmax) Following Single Dose of Quizartinib With or Without Efavirenz |
130.0; 238.0; 11.0; 34.4 | — |
| PRIMARY Time to Maximum Plasma Concentration (Tmax) Following Single Dose of Quizartinib With or Without Efavirenz |
2.0; 4.0; 4.0; 4.0 | — |
| PRIMARY Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) Following Single Dose of Quizartinib With or Without Efavirenz |
2730; 23600; 185; 4110 | — |
| PRIMARY Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) Following Single Dose of Quizartinib With or Without Efavirenz |
2760; 26000; 208; 4540 | — |
| PRIMARY Terminal Half-Life (t1/2) Following Single Dose of Quizartinib With or Without Efavirenz |
23.8; 136; 11.9; 135 | — |
| PRIMARY Metabolite to Parent Ratio (MPR) Based on Area Under the Curve for Active Metabolite AC886 Following Single Dose of Quizartinib With or Without Efavirenz |
0.0675; 0.186; 0.0762; 0.1880 | — |
| PRIMARY Total Apparent Clearance (CL/F) for Quizartinib Following Single Dose of Quizartinib With or Without Efavirenz |
12.210; 1.1849 | — |
| PRIMARY Volume of Distribution in the Terminal Phase (Vz/F) for Quizartinib Following Single Dose of Quizartinib With or Without Efavirenz |
359.9; 214.9 | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events Following Single Dose of Quizartinib With or Without Efavirenz |
13; 5 | — |
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) 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
Data sourced from ClinicalTrials.gov (NCT04459598). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.