A Phase 1, Open Label, Randomized, Parallel Drug Interaction Study to Evaluate the Effect of a CYP3A Weak Inducer Rufinamide on the Pharmacokinetics of Quizartinib in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Pharmacokinetic Parameter: Cmax
研究概览
简要总结
This study will evaluate the effect of CYP3A weak inducer rufinamide on the pharmacokinetics (PK) of Quizartinib in healthy subjects
详细描述
This is a clinical pharmacology study with 2 treatment groups (Test treatment group receiving both rufinamide weak CYP3A inducer and quizartinib and Reference treatment group receiving quizartinib only) investigating the effect of rufinamide on the PK of quizartinib in healthy subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
No masking.
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male and female subjects 18 to 55 years of age (inclusive), with a BMI of 18 kg/m2 to 32 kg/m2 (inclusive) at Screening.
- •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.
- •Liver function test results (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and total bilirubin [TBbil]) must be equal to or below the upper limit of normal (ULN). Hemoglobin levels must be ≥11.5 g/dL for female subjects and ≥12.5 g/dL for male subjects.
- •In females, documented surgical sterilization (i.e., 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 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.
- •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 dose of quizartini
排除标准
- •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.
- •History of a clinically significant illness, in the opinion of the Investigator, within 4 weeks prior to administration of quizartinib.
- •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.
- •Females who are pregnant or breastfeeding
- •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 using the Cockcroft-Gault Equation) at Screening.
研究组 & 干预措施
Treatment Group A (Test)
On Day 1 through Day 32, participants will receive an oral dose of 400-mg of rufinamide twice daily (BID). In addition, on Day 12, subjects will receive an oral single dose of 60-mg quizartinib
干预措施: Quizartinib (Drug)
Treatment Group A (Test)
On Day 1 through Day 32, participants will receive an oral dose of 400-mg of rufinamide twice daily (BID). In addition, on Day 12, subjects will receive an oral single dose of 60-mg quizartinib
干预措施: Rufinamide (Drug)
Treatment Group B (Reference)
On Day 1, participants will receive an oral dose of 60-mg quizartinib
干预措施: Quizartinib (Drug)
结局指标
主要结局
Pharmacokinetic Parameter: Cmax
时间窗: From day of first dose, Day 1, up to Day 33
Cmax is defined as maximum concentration, determined directly from individual concentration-time data
Pharmacokinetic Parameter: AUClast
时间窗: From day of first dose, Day 1, up to Day 33
AUClast is defined as area under the concentration-time curve from time-zero to the time of the last quantifiable concentration; calculated using the linear up log down
Pharmacokinetic Parameter: AUCinf
时间窗: From day of first dose, Day 1, up to Day 33
AUCinf is defined as area under the concentration-time curve from time-zero extrapolated to infinity
次要结局
- Treatment Emergent Adverse Events (TEAEs)(From day of first dose, Day 1 up to the last day of Safety Follow-up, up to approximately 40 days)