Early Phase 1
N=20
A Study of the Effect of Quizartinib on the Pharmacokinetics of the P-gp Substrate Dabigatran Etexilate in Healthy Participants
Healthy Subjects · Drug-drug Interaction · Pharmacokinetics · Quizartinib
Bottom Line
View on ClinicalTrials.gov: NCT04459585 ↗Enrolled (actual)
20
Serious AEs
0.0%
Results posted
Jul 2021
Primary outcome: Primary: Maximum Plasma Concentration (Cmax) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib — 192; 239; 159; 201 ng/mL
Study Design & Population
- Study type
- Interventional
- Phase
- Early Phase 1
- Interventions
- Dabigatran Etexilate Mesylate (Drug); Quizartinib (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Daiichi Sankyo Co., Ltd.
- Primary completion
- Oct 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Plasma Concentration (Cmax) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib |
192; 239; 159; 201 | — |
| PRIMARY Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib |
1720; 2100; 1390; 1710 | — |
| PRIMARY Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib |
1740; 2140; 1420; 1730 | — |
| SECONDARY Time of Maximum Plasma Concentration (Tmax) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib |
2.0; 2.0; 2.0; 2.0 | — |
| SECONDARY Terminal Elimination Half-Life (T1/2) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib |
15.4; 18.1; 14.2; 14.1 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants |
250; 25.7 | — |
| SECONDARY Time of Maximum Plasma Concentration (Tmax) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants |
3.0; 8.0 | — |
| SECONDARY Area Under the Plasma Concentration-Time Curve From Time 0 to 74 Hours (AUClast,74) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants |
9390; 1350 | — |
| SECONDARY Number of Participants Reporting Treatment-Emergent Adverse Events (TEAE) Relatedness to Study Medication Following Single Dose of Dabigatran Without and With Quizartinib in Participants |
0; 2; 0; 1 | — |
Summary
The purpose of this study is to investigate the one-way drug-drug interaction potential of quizartinib on dabigatran etexilate in healthy adult participants.
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 million international (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 hours prior to check-in and during confinement
- Positive serology for hepatitis B surface antigen (HBsAg) and hepatitis C virus [HCV] (healthy participants), hepatitis A virus (HAV) immunoglobulin M, or anti-human immunodeficiency virus (HIV) Type 1 and Type 2 (all subjects)
- 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 (NCT04459585). 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.