Healthy Subjects, Drug-drug Interaction, Pharmacokinetics, Quizartinib
Conditions
Keywords
Healthy subjects, Drug-drug Interaction, Pharmacokinetics, Quizartinib, P-gp, Dabigatran Etexilate
Brief 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.
Detailed description
This study will evaluate the potential intestinal inhibitory effect of quizartinib on the pharmacokinetics of a Pgp substrate dabigatran etexilate in healthy participants. The hypothesis for this clinical study is that quizartinib, as a P-gp inhibitor, may increase the systemic exposure (measured by area under the concentration-time curve \[AUC\] and maximum concentration \[Cmax\]) of P-gp substrates that may be sensitive to intestinal P-gp inhibition.
Interventions
Single oral 150 mg capsule dose
DRUGQuizartinib
Single oral 60 mg dose of quizartinib administered as two 30 mg tablets (26.5 mg free base per tablet)
Sponsors
Daiichi Sankyo Co., Ltd.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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) \< 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) * 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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib | Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose) | Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was calculated using non-compartmental analysis. |
| 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 | Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose) | Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method and was calculated using non-compartmental analysis. |
| 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 | Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose) | Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity and was calculated using non-compartmental analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time of Maximum Plasma Concentration (Tmax) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants | Period 2 Day 5 (Pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose) | Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was calculated using non-compartmental analysis. Tmax was assessed for Quizartinib and Metabolite AC886. |
| Time of Maximum Plasma Concentration (Tmax) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib | Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose) | Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was calculated using non-compartmental analysis. |
| Number of Participants Reporting Treatment-Emergent Adverse Events (TEAE) Relatedness to Study Medication Following Single Dose of Dabigatran Without and With Quizartinib in Participants | Up to 2 months | A Treatment-Emergent Adverse Events (TEAE) is defined as any event not present prior to the initiation of the drug treatment of the drug treatment or any event already present that worsens in either intensity or frequency following exposure to the drug treatment. Number of any TEAE that is related and unrelated to study medication is presented. |
| 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 | Period 2 Day 5 (Pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose) | Area Under the Plasma Concentration-Time Curve From Time 0 to 74 Hours (AUClast,74) is defined as area under the plasma concentration-time curve to the last quantifiable concentration post dose at 74 hours and was calculated using non-compartmental analysis. AUClast,74 was assessed for Quizartinib and Metabolite AC886. |
| Terminal Elimination Half-Life (T1/2) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib | Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose) | Terminal Elimination Half-Life (T1/2) is defined as terminal elimination half-life and was calculated using non-compartmental analysis. |
| Maximum Plasma Concentration (Cmax) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants | Period 2 Day 5 (Pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose) | Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was calculated using non-compartmental analysis. Cmax was assessed for Quizartinib and Metabolite AC886. |
Countries
United States
Participant flow
Recruitment details
A total of 20 participants who met all inclusion criteria and no exclusion criteria were enrolled from 28 Aug 2020 to 20 Oct 2020 at 1 clinic in the United States.
Pre-assignment details
This study consisted of two treatment periods. Following a Screening Period of 21 days, eligible participants received only dabigatran etexilate (Reference Treatment) on Day 1 of Period 1 followed by quizartinib and dabigatran etexilate administration (Test Treatment) on Day 5 of Period 2.
Participants by arm
| Arm | Count |
|---|---|
| Dabigatran Etexilate/Dabigatran Etexilate + Quizartinib Participants who received a single oral dose of 150mg dabigatran etexilate on Day 1 of Period 1 and then received a single oral dose of 60mg quizartinib 2 hours prior to the administration of a single oral dose of 150mg dabigatran etexilate on the morning of Day 5 of Period 2. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Dabigatran Etexilate/Dabigatran Etexilate + Quizartinib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Age, Continuous | 39.0 years STANDARD_DEVIATION 10.37 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 0 / 20 | 3 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
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
Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity and was calculated using non-compartmental analysis.
Time frame: Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)
Population: The pharmacokinetic parameter of Area Under the Plasma Concentration-Time Curve up to Infinity was assessed using the Pharmacokinetic Analysis Set except for 1 participant that did not meet the protocol inclusion criteria for this analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: Dabigatran Etexilate | 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 | Total Dabigatran | 1740 ng*h/mL | Standard Deviation 902 |
| Period 1: Dabigatran Etexilate | 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 | Free Dabigatran | 1420 ng*h/mL | Standard Deviation 760 |
| Period 2: Dabigatran Etexilate + Quizartinib | 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 | Total Dabigatran | 2140 ng*h/mL | Standard Deviation 1280 |
| Period 2: Dabigatran Etexilate + Quizartinib | 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 | Free Dabigatran | 1730 ng*h/mL | Standard Deviation 1100 |
Comparison: Statistical comparison was analyzed for Total Dabigatran.90% CI: [79.38, 160.79]
Comparison: Statistical comparison was analyzed for Free Dabigatran.90% CI: [76.77, 159.68]
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
Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method and was calculated using non-compartmental analysis.
Time frame: Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)
Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: Dabigatran Etexilate | 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 | Total Dabigatran | 1720 ng*h/mL | Standard Deviation 870 |
| Period 1: Dabigatran Etexilate | 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 | Free Dabigatran | 1390 ng*h/mL | Standard Deviation 736 |
| Period 2: Dabigatran Etexilate + Quizartinib | 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 | Total Dabigatran | 2100 ng*h/mL | Standard Deviation 1280 |
| Period 2: Dabigatran Etexilate + Quizartinib | 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 | Free Dabigatran | 1710 ng*h/mL | Standard Deviation 1100 |
Comparison: Statistical comparison was analyzed for Total Dabigatran.90% CI: [78.51, 157.97]
Comparison: Statistical comparison was analyzed for Free Dabigatran.90% CI: [77.35, 159.51]
Primary
Maximum Plasma Concentration (Cmax) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib
Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was calculated using non-compartmental analysis.
Time frame: Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)
Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: Dabigatran Etexilate | Maximum Plasma Concentration (Cmax) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib | Total Dabigatran | 192 ng/mL | Standard Deviation 94.5 |
| Period 1: Dabigatran Etexilate | Maximum Plasma Concentration (Cmax) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib | Free Dabigatran | 159 ng/mL | Standard Deviation 82.2 |
| Period 2: Dabigatran Etexilate + Quizartinib | Maximum Plasma Concentration (Cmax) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib | Total Dabigatran | 239 ng/mL | Standard Deviation 141 |
| Period 2: Dabigatran Etexilate + Quizartinib | Maximum Plasma Concentration (Cmax) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib | Free Dabigatran | 201 ng/mL | Standard Deviation 127 |
Comparison: Statistical comparison was analyzed for Total Dabigatran.90% CI: [77.57, 161.35]
Comparison: Statistical comparison was analyzed for Free Dabigatran.90% CI: [77.2, 165.34]
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
Area Under the Plasma Concentration-Time Curve From Time 0 to 74 Hours (AUClast,74) is defined as area under the plasma concentration-time curve to the last quantifiable concentration post dose at 74 hours and was calculated using non-compartmental analysis. AUClast,74 was assessed for Quizartinib and Metabolite AC886.
Time frame: Period 2 Day 5 (Pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)
Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: Dabigatran Etexilate | 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 | Quizartinib | 9390 ng*h/mL | Standard Deviation 1660 |
| Period 1: Dabigatran Etexilate | 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 | AC886 | 1350 ng*h/mL | Standard Deviation 495 |
Secondary
Maximum Plasma Concentration (Cmax) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants
Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was calculated using non-compartmental analysis. Cmax was assessed for Quizartinib and Metabolite AC886.
Time frame: Period 2 Day 5 (Pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)
Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Period 1: Dabigatran Etexilate | Maximum Plasma Concentration (Cmax) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants | Quizartinib | 250 ng/mL | Standard Deviation 50.8 |
| Period 1: Dabigatran Etexilate | Maximum Plasma Concentration (Cmax) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants | AC886 | 25.7 ng/mL | Standard Deviation 8.71 |
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
A Treatment-Emergent Adverse Events (TEAE) is defined as any event not present prior to the initiation of the drug treatment of the drug treatment or any event already present that worsens in either intensity or frequency following exposure to the drug treatment. Number of any TEAE that is related and unrelated to study medication is presented.
Time frame: Up to 2 months
Population: TEAEs were assessed using the Safety Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Period 1: Dabigatran Etexilate | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAE) Relatedness to Study Medication Following Single Dose of Dabigatran Without and With Quizartinib in Participants | Related | 0 Participants |
| Period 1: Dabigatran Etexilate | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAE) Relatedness to Study Medication Following Single Dose of Dabigatran Without and With Quizartinib in Participants | Unrelated | 0 Participants |
| Period 2: Dabigatran Etexilate + Quizartinib | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAE) Relatedness to Study Medication Following Single Dose of Dabigatran Without and With Quizartinib in Participants | Related | 2 Participants |
| Period 2: Dabigatran Etexilate + Quizartinib | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAE) Relatedness to Study Medication Following Single Dose of Dabigatran Without and With Quizartinib in Participants | Unrelated | 1 Participants |
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
Terminal Elimination Half-Life (T1/2) is defined as terminal elimination half-life and was calculated using non-compartmental analysis.
Time frame: Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)
Population: The pharmacokinetic parameter of Terminal Elimination Half-Life was assessed using the Pharmacokinetic Analysis Set except for 1 participant that did not meet the protocol inclusion criteria for this analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: Dabigatran Etexilate | Terminal Elimination Half-Life (T1/2) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib | Total Dabigatran | 15.4 hours | Standard Deviation 4.4 |
| Period 1: Dabigatran Etexilate | Terminal Elimination Half-Life (T1/2) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib | Free Dabigatran | 14.2 hours | Standard Deviation 4.2 |
| Period 2: Dabigatran Etexilate + Quizartinib | Terminal Elimination Half-Life (T1/2) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib | Total Dabigatran | 18.1 hours | Standard Deviation 17 |
| Period 2: Dabigatran Etexilate + Quizartinib | Terminal Elimination Half-Life (T1/2) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib | Free Dabigatran | 14.1 hours | Standard Deviation 6.6 |
Secondary
Time of Maximum Plasma Concentration (Tmax) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants
Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was calculated using non-compartmental analysis. Tmax was assessed for Quizartinib and Metabolite AC886.
Time frame: Period 2 Day 5 (Pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)
Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Period 1: Dabigatran Etexilate | Time of Maximum Plasma Concentration (Tmax) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants | Quizartinib | 3.0 hours |
| Period 1: Dabigatran Etexilate | Time of Maximum Plasma Concentration (Tmax) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants | AC886 | 8.0 hours |
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
Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was calculated using non-compartmental analysis.
Time frame: Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)
Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Period 1: Dabigatran Etexilate | Time of Maximum Plasma Concentration (Tmax) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib | Total Dabigatran | 2.0 hours |
| Period 1: Dabigatran Etexilate | Time of Maximum Plasma Concentration (Tmax) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib | Free Dabigatran | 2.0 hours |
| Period 2: Dabigatran Etexilate + Quizartinib | Time of Maximum Plasma Concentration (Tmax) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib | Total Dabigatran | 2.0 hours |
| Period 2: Dabigatran Etexilate + Quizartinib | Time of Maximum Plasma Concentration (Tmax) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib | Free Dabigatran | 2.0 hours |