Healthy Subjects
Conditions
Keywords
quizartinib
Brief summary
This study will evaluate the impact of rapid acceleration in the heart rate on the QT prolongation of quizartinib.
Detailed description
This is a QT assessment study of quizartinib when given as a single oral dose of 90 mg in 70 healthy subjects.
Interventions
DRUGQuizartinib
Participants will receive a single oral dose of 90 mg
OTHERPlacebo
Participants will receive a single oral dose of 90 mg
Sponsors
Daiichi Sankyo
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is a single-blinded study where only the participants will be blinded to the treatment being administered.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: 1. Male and female subjects 18 to 55 years of age (inclusive), with a BMI of 18 kg/m2 to 32 kg/m2 (inclusive) with a minimum body weight of 40 kg at Screening. 2. Has vital signs (measured after subject has been supine for at least 5 minutes) at Screening within the following ranges: heart rate: 50-100 beats per minute (bpm); systolic blood pressure (BP): 90-145 mmHg; diastolic BP: 50-95 mmHg. Out-of-range vital signs may be repeated once. 3. Liver function test results (alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], and total bilirubin \[TBil\]) must be equal to or below the upper limit of normal. 4. Hemoglobin levels must ≥11.5 g/dL for female subjects and ≥12.5 g/dL for male subjects. 5. In females, documented surgical sterilization (ie, documented hysterectomy, bilateral tubal ligation, or bilateral salpingo-oophorectomy, Essure® with hysterosalpingogram \[documentation to confirm tubal occlusion 12 weeks after procedure\]), postmenopausal status for at least 1 year (follicle stimulating hormone \[FSH\] \> 40 mIU/mL serum and estradiol \<40 pg/mL \[\<147 pmol/L\] at Screening), or agreement to have a sterile male partner, or agreement to use 1 of the protocol-approved means of contraception from Screening until 7 months after the dose of quizartinib. 6. In males, documented surgical sterilization, or sexual abstinence, or agreement to use 1 of the protocol-approved means of contraception from Screening until 4 months after the single dose of quizartinib. Key
Exclusion criteria
1. Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including lab abnormality) that could interfere with subject's safety, obtaining informed consent, compliance to the study procedures, or the validity of the study results. 2. In the opinion of the investigator, history of a clinically significant illness within 4 weeks prior to administration of quizartinib. 3. History or presence of an abnormal ECG, which, in the investigator's opinion, is clinically significant and/or a QT interval corrected for heart rate using Fridericia's formula (QTcF) \>450 milliseconds (ms) at Screening 4. Females who are pregnant or breastfeeding 5. Laboratory results (serum chemistry, hematology, and urinalysis) outside the normal range, if considered clinically significant by the investigator. Estimated creatinine clearance (CrCl) \< 90 mL/min (calculated by Cockcroft-Gault equation) at Screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Heart Rate | Day 1 and Day 2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Parameter: AUClast | Days 1, 2 and 3 | Area under the concentration-time curve from time-zero to the time of the last quantifiable concentration; calculated using the linear up log down |
| Treatment Emergent Adverse Events (TEAEs) | From Day 1 up to the last day of Safety Follow-up (approximately 16 days) | TEAEs are defined as new AEs that occur after the first dose of study drug, including 14 days after last dose of study drug to end of the sentence |
| Pharmacokinetic Parameter: Cmax | Days 1, 2 and 3 | Maximum concentration, determined directly from individual concentration-time data |
| Pharmacokinetic Parameter: Tmax | Days 1, 2 and 3 | Time of the maximum concentration |
Countries
United States
Outcome results
None listed