Drug-drug Interaction, Healthy Subjects, Pharmacokinetics, Quizartinib
Conditions
Keywords
Healthy Subjects, Drug-drug Interaction, Pharmacokinetics, Quizartinib, CYP3A Inducer
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 metabolite AC886.
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 moderate CYP3A inducer efavirenz on the single dose (60 mg) quizartinib pharmacokinetics in healthy participants.
Interventions
DRUGEfavirenz
Single oral dose, 600-mg tablet
DRUGQuizartinib
Single oral dose, 60 mg (2 x 30 mg) tablets
Sponsors
Daiichi Sankyo Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Volume of Distribution in the Terminal Phase (Vz/F) for Quizartinib Following Single Dose of Quizartinib With or Without Efavirenz | Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose | Volume of Distribution in the Terminal Phase (Vz/F) is defined as volume of distribution in the terminal phase and was calculated using non-compartmental analysis. |
| Maximum Plasma Concentration (Cmax) Following Single Dose of Quizartinib With or Without Efavirenz | Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose | Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was an observed value for the study. Cmax was assessed for Quizartinib and active metabolite AC886. |
| Time to Maximum Plasma Concentration (Tmax) Following Single Dose of Quizartinib With or Without Efavirenz | Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose | Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was an observed value from the study. Tmax was assessed for Quizartinib and active metabolite AC886. |
| 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 | Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib 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. AUClast was assessed for Quizartinib and active metabolite AC886. |
| Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) Following Single Dose of Quizartinib With or Without Efavirenz | Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib 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. AUCinf was assessed for Quizartinib and active metabolite AC886. |
| Terminal Half-Life (t1/2) Following Single Dose of Quizartinib With or Without Efavirenz | Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose | Terminal Elimination Half-Life (t1/2) is defined as terminal elimination half-life and was calculated using non-compartmental analysis. AUClast was assessed for Quizartinib and active metabolite AC886. Half-life (t1/2) was assessed for Quizartinib and active metabolite AC886. |
| Metabolite to Parent Ratio (MPR) Based on Area Under the Curve for Active Metabolite AC886 Following Single Dose of Quizartinib With or Without Efavirenz | Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose | AUCinf is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity and AUClast is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method. MPR is defined as a metabolite to parent ratio with metabolite as the numerator and the parent as the denominator. MPR corrected for molecular weight of AC886 of AUCinf and AUClast are reported and were calculated using non-compartmental analysis. |
| Total Apparent Clearance (CL/F) for Quizartinib Following Single Dose of Quizartinib With or Without Efavirenz | Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose | Total Apparent Clearance (CL/F) is defined as total apparent clearance and was calculated using non-compartmental analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events Following Single Dose of Quizartinib With or Without Efavirenz | Baseline up to 30 days post last dose, up to approximately 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. |
Countries
United States
Participant flow
Recruitment details
A total of 32 participants who met all inclusion criteria and no exclusion criteria were enrolled from 19 Aug 2020 to 14 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 were randomized in a 1:1 ratio to 1 of 2 treatment groups. Treatment Group A received efavirenz once daily on Day 1 and continued the regimen through Day 35 and a single dose of quizartinib on Day 15. Treatment Group B received a single dose of quizartinib on Day 1.
Participants by arm
| Arm | Count |
|---|---|
| Efavirenz 600 mg + Quizartinib 60 mg Participants who received efavirenz 600 mg once daily (QD) for 34 days and a single, oral dose of quizartinib 60 mg on Day 15 concurrently with efavirenz. | 16 |
| Quizartinib 60 mg Participants who received a single, oral dose of quizartinib 60 mg on Day 1. | 16 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Efavirenz 600 mg + Quizartinib 60 mg | Quizartinib 60 mg |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants | 16 Participants | 16 Participants |
| Age, Continuous | 39.6 years STANDARD_DEVIATION 10.01 | 40 years STANDARD_DEVIATION 10.05 | 38.7 years STANDARD_DEVIATION 10.22 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 18 Participants | 9 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 5 Participants | 7 Participants |
| Sex: Female, Male Female | 6 Participants | 1 Participants | 5 Participants |
| Sex: Female, Male Male | 26 Participants | 15 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 13 / 16 | 5 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
Primary
Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) Following Single Dose of Quizartinib With or Without Efavirenz
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. AUCinf was assessed for Quizartinib and active metabolite AC886.
Time frame: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose
Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set except for 1 participant from the Efavirenz 600 mg + Quizartinib 60 mg group due to insufficient data. Data from participants where AUCinf based on extrapolation was greater than 20% was also excluded from the Efavirenz 600 mg + Quizartinib 60 mg group and Quizartinib 60 mg group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Efavirenz 600 mg + Quizartinib 60 mg | Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) Following Single Dose of Quizartinib With or Without Efavirenz | Quizartinib | 2760 ng*h/mL | Standard Deviation 1170 |
| Efavirenz 600 mg + Quizartinib 60 mg | Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) Following Single Dose of Quizartinib With or Without Efavirenz | AC886 | 208 ng*h/mL | Standard Deviation 183 |
| Quizartinib 60 mg | Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) Following Single Dose of Quizartinib With or Without Efavirenz | Quizartinib | 26000 ng*h/mL | Standard Deviation 9880 |
| Quizartinib 60 mg | Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) Following Single Dose of Quizartinib With or Without Efavirenz | AC886 | 4540 ng*h/mL | Standard Deviation 1410 |
Comparison: Statistical comparison was analyzed for Quizartinib.90% CI: [7.73, 13.7]
Comparison: Statistical comparison was analyzed for AC886.90% CI: [2.62, 5.76]
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
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. AUClast was assessed for Quizartinib and active metabolite AC886.
Time frame: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose
Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set except for 1 participant from the Efavirenz 600 mg + Quizartinib 60 mg group due to insufficient data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Efavirenz 600 mg + Quizartinib 60 mg | 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 | Quizartinib | 2730 ng*h/mL | Standard Deviation 1160 |
| Efavirenz 600 mg + Quizartinib 60 mg | 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 | AC886 | 185 ng*h/mL | Standard Deviation 177 |
| Quizartinib 60 mg | 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 | Quizartinib | 23600 ng*h/mL | Standard Deviation 8420 |
| Quizartinib 60 mg | 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 | AC886 | 4110 ng*h/mL | Standard Deviation 1320 |
Comparison: Statistical comparison was analyzed for Quizartinib.90% CI: [8.47, 14.56]
Comparison: Statistical comparison was analyzed for AC886.90% CI: [2.47, 5.45]
Primary
Maximum Plasma Concentration (Cmax) Following Single Dose of Quizartinib With or Without Efavirenz
Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was an observed value for the study. Cmax was assessed for Quizartinib and active metabolite AC886.
Time frame: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose
Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set except for 1 participant from the Efavirenz 600 mg + Quizartinib 60 mg group due to insufficient data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Efavirenz 600 mg + Quizartinib 60 mg | Maximum Plasma Concentration (Cmax) Following Single Dose of Quizartinib With or Without Efavirenz | AC886 | 11.0 ng/mL | Standard Deviation 5.35 |
| Efavirenz 600 mg + Quizartinib 60 mg | Maximum Plasma Concentration (Cmax) Following Single Dose of Quizartinib With or Without Efavirenz | Quizartinib | 130.0 ng/mL | Standard Deviation 36.1 |
| Quizartinib 60 mg | Maximum Plasma Concentration (Cmax) Following Single Dose of Quizartinib With or Without Efavirenz | Quizartinib | 238.0 ng/mL | Standard Deviation 76.9 |
| Quizartinib 60 mg | Maximum Plasma Concentration (Cmax) Following Single Dose of Quizartinib With or Without Efavirenz | AC886 | 34.4 ng/mL | Standard Deviation 18.2 |
Comparison: Statistical comparison was analyzed for Quizartinib.90% CI: [45.24, 67.46]
Comparison: Statistical comparison was analyzed for AC886.90% CI: [23.79, 44.05]
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
AUCinf is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity and AUClast is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method. MPR is defined as a metabolite to parent ratio with metabolite as the numerator and the parent as the denominator. MPR corrected for molecular weight of AC886 of AUCinf and AUClast are reported and were calculated using non-compartmental analysis.
Time frame: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose
Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set except for 1 participant from the Efavirenz 600 mg + Quizartinib 60 mg group due to insufficient data. Data from participants where AUCinf based on extrapolation was greater than 20% was also excluded from MPR AUCinf.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Efavirenz 600 mg + Quizartinib 60 mg | Metabolite to Parent Ratio (MPR) Based on Area Under the Curve for Active Metabolite AC886 Following Single Dose of Quizartinib With or Without Efavirenz | MPR AUClast | 0.0675 ratio | Standard Deviation 0.0403 |
| Efavirenz 600 mg + Quizartinib 60 mg | Metabolite to Parent Ratio (MPR) Based on Area Under the Curve for Active Metabolite AC886 Following Single Dose of Quizartinib With or Without Efavirenz | MPR AUCinf | 0.0762 ratio | Standard Deviation 0.0395 |
| Quizartinib 60 mg | Metabolite to Parent Ratio (MPR) Based on Area Under the Curve for Active Metabolite AC886 Following Single Dose of Quizartinib With or Without Efavirenz | MPR AUClast | 0.186 ratio | Standard Deviation 0.0753 |
| Quizartinib 60 mg | Metabolite to Parent Ratio (MPR) Based on Area Under the Curve for Active Metabolite AC886 Following Single Dose of Quizartinib With or Without Efavirenz | MPR AUCinf | 0.1880 ratio | Standard Deviation 0.0777 |
Primary
Terminal Half-Life (t1/2) Following Single Dose of Quizartinib With or Without Efavirenz
Terminal Elimination Half-Life (t1/2) is defined as terminal elimination half-life and was calculated using non-compartmental analysis. AUClast was assessed for Quizartinib and active metabolite AC886. Half-life (t1/2) was assessed for Quizartinib and active metabolite AC886.
Time frame: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose
Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set except for 1 participant from the Efavirenz 600 mg + Quizartinib 60 mg group due to insufficient data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Efavirenz 600 mg + Quizartinib 60 mg | Terminal Half-Life (t1/2) Following Single Dose of Quizartinib With or Without Efavirenz | AC886 | 11.9 hours | Standard Deviation 5.5 |
| Efavirenz 600 mg + Quizartinib 60 mg | Terminal Half-Life (t1/2) Following Single Dose of Quizartinib With or Without Efavirenz | Quizartinib | 23.8 hours | Standard Deviation 7.4 |
| Quizartinib 60 mg | Terminal Half-Life (t1/2) Following Single Dose of Quizartinib With or Without Efavirenz | Quizartinib | 136 hours | Standard Deviation 40.1 |
| Quizartinib 60 mg | Terminal Half-Life (t1/2) Following Single Dose of Quizartinib With or Without Efavirenz | AC886 | 135 hours | Standard Deviation 33.5 |
Primary
Time to Maximum Plasma Concentration (Tmax) Following Single Dose of Quizartinib With or Without Efavirenz
Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was an observed value from the study. Tmax was assessed for Quizartinib and active metabolite AC886.
Time frame: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose
Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set except for 1 participant from the Efavirenz 600 mg + Quizartinib 60 mg group due to insufficient data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Efavirenz 600 mg + Quizartinib 60 mg | Time to Maximum Plasma Concentration (Tmax) Following Single Dose of Quizartinib With or Without Efavirenz | Quizartinib | 2.0 hours |
| Efavirenz 600 mg + Quizartinib 60 mg | Time to Maximum Plasma Concentration (Tmax) Following Single Dose of Quizartinib With or Without Efavirenz | AC886 | 4.0 hours |
| Quizartinib 60 mg | Time to Maximum Plasma Concentration (Tmax) Following Single Dose of Quizartinib With or Without Efavirenz | Quizartinib | 4.0 hours |
| Quizartinib 60 mg | Time to Maximum Plasma Concentration (Tmax) Following Single Dose of Quizartinib With or Without Efavirenz | AC886 | 4.0 hours |
Primary
Total Apparent Clearance (CL/F) for Quizartinib Following Single Dose of Quizartinib With or Without Efavirenz
Total Apparent Clearance (CL/F) is defined as total apparent clearance and was calculated using non-compartmental analysis.
Time frame: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose
Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set except for 1 participant from the Efavirenz 600 mg + Quizartinib 60 mg group due to insufficient data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Efavirenz 600 mg + Quizartinib 60 mg | Total Apparent Clearance (CL/F) for Quizartinib Following Single Dose of Quizartinib With or Without Efavirenz | 12.210 L/h | Standard Deviation 7.6937 |
| Quizartinib 60 mg | Total Apparent Clearance (CL/F) for Quizartinib Following Single Dose of Quizartinib With or Without Efavirenz | 1.1849 L/h | Standard Deviation 0.51388 |
Primary
Volume of Distribution in the Terminal Phase (Vz/F) for Quizartinib Following Single Dose of Quizartinib With or Without Efavirenz
Volume of Distribution in the Terminal Phase (Vz/F) is defined as volume of distribution in the terminal phase and was calculated using non-compartmental analysis.
Time frame: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose
Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set except for 1 participant from the Efavirenz 600 mg + Quizartinib 60 mg group due to insufficient data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Efavirenz 600 mg + Quizartinib 60 mg | Volume of Distribution in the Terminal Phase (Vz/F) for Quizartinib Following Single Dose of Quizartinib With or Without Efavirenz | 359.9 L | Standard Deviation 102.23 |
| Quizartinib 60 mg | Volume of Distribution in the Terminal Phase (Vz/F) for Quizartinib Following Single Dose of Quizartinib With or Without Efavirenz | 214.9 L | Standard Deviation 59.82 |
Secondary
Number of Participants With Treatment-emergent Adverse Events Following Single Dose of Quizartinib With or Without Efavirenz
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: Baseline up to 30 days post last dose, up to approximately 2 months
Population: TEAEs were assessed using the Safety Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Efavirenz 600 mg + Quizartinib 60 mg | Number of Participants With Treatment-emergent Adverse Events Following Single Dose of Quizartinib With or Without Efavirenz | 13 Participants |
| Quizartinib 60 mg | Number of Participants With Treatment-emergent Adverse Events Following Single Dose of Quizartinib With or Without Efavirenz | 5 Participants |