A Phase 1 Open-Label, Fixed-Sequence Drug-Drug Interaction Study to Evaluate the Effects of Steady-state Itraconazole and Rifampin on the Single-dose Pharmacokinetics of Lazertinib Tablets in Healthy Adult Participants
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
- Cohort 1 and 2: Area Under the Plasma Concentration-time Curve from Time 0 to 120 Hours (AUC [0-120h]) of Lazertinib
研究概览
简要总结
The purpose of this study is to evaluate the effects of multiple doses of strong cytochrome P450 (CYP) 3A4 inhibitor itraconazole and strong CYP3A4 inducer rifampin on the single dose pharmacokinetics (PK) of lazertinib in healthy adult participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •A woman must not be of childbearing potential and must have a negative serum beta-human chorionic gonadotropin (Beta HCG) pregnancy test at screening
- •Hormone replacement therapy (if applicable) must have been discontinued at least 28 days prior to the first dose of study drug (Cohort 2 only)
- •Participants must have a body mass index (BMI) between 18.0 and 32.0 kilogram per meter square (kg/m^2, inclusive (BMI = weight/height^2), and body weight not less than 50 kg at screening
- •Participants must be healthy based on physical examination, medical history, and vital signs (pulse and body temperature), performed at screening
- •Male participants must agree to use an adequate contraception method
排除标准
- •History of or current clinically significant medical illness that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results
- •History of infection suspected or confirmed to be related to Coronavirus disease 2019 (COVID-19) within 4 weeks before intake of study drug
- •Participant has known allergies, hypersensitivity, or intolerance to lazertinib or its excipients or to itraconazole and rifampin
- •Participant has contraindications to the use itraconazole and rifampin per local prescribing information
- •Use of any cytochrome P450 (CYP) 3A4 inhibitors or inducers (other than per-protocol itraconazole/rifampin administration) within 4 weeks before the first dose of the study drug is scheduled until completion of the study
研究组 & 干预措施
Cohort 1: Lazertinib plus Itraconazole
Participants will receive a single oral dose of lazertinib tablets in Treatment Period 1 followed by itraconazole capsules orally along with a single oral dose of lazertinib tablet in Treatment Period 2.
干预措施: Lazertinib (Drug)
Cohort 1: Lazertinib plus Itraconazole
Participants will receive a single oral dose of lazertinib tablets in Treatment Period 1 followed by itraconazole capsules orally along with a single oral dose of lazertinib tablet in Treatment Period 2.
干预措施: Itraconazole (Drug)
Cohort 2: Lazertinib plus Rifampin
Participants will receive a single oral dose of lazertinib tablets in Treatment Period 1 followed by rifampin capsules orally along with a single oral dose of lazertinib tablet in Treatment Period 2.
干预措施: Lazertinib (Drug)
Cohort 2: Lazertinib plus Rifampin
Participants will receive a single oral dose of lazertinib tablets in Treatment Period 1 followed by rifampin capsules orally along with a single oral dose of lazertinib tablet in Treatment Period 2.
干预措施: Rifampin (Drug)
结局指标
主要结局
Cohort 1 and 2: Area Under the Plasma Concentration-time Curve from Time 0 to 120 Hours (AUC [0-120h]) of Lazertinib
时间窗: Predose up to 120 hours post dose
AUC (0-120h) is defined as area under the plasma concentration-time curve from time 0 to 120 hours postdose.
Cohort 1 and 2: Maximum Plasma Concentration (Cmax) of Lazertinib
时间窗: Predose up to 120 hours post dose
Cmax is defined as maximum plasma concentration.
Cohort 1 and 2: Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUC [0-inf]) of Lazertinib
时间窗: Predose up to 120 hours post dose
AUC (0-inf) is defined as area under the plasma concentration-time curve from time 0 to infinity, calculated as the sum of AUC(0-last)+C(last)/ lambda(z), where C(last) is the last observed measurable (non-below limit of quantification) concentration.
Cohort 1 and 2: Area Under the Plasma Concentration-time Curve from Time Zero to Time of Last Quantifiable Timepoint (AUC [0-last]) of Lazertinib
时间窗: Predose up to 120 hours post dose
AUC (0-last) is defined as area under the plasma concentration-time curve from time 0 to time of last quantifiable timepoint.
Cohort 1 and 2: Percentage of Area Under the Plasma Concentration from time Zero to Infinite time obtained by Extrapolation (%AUC [0-inf],ex) of Lazertinib
时间窗: Predose up to 120 hours post dose
%AUC (0-inf),ex is defined as percentage of area under the plasma concentration from time zero to infinite time obtained by extrapolation, calculated as (AUC \[0-infinity\] minus AUC \[0-last\]/AUC \[0-infinity\])\*100.
次要结局
- Cohort 1 and Cohort 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability(Up to 65 days (Cohort 1) and up to 70 days (Cohort 2))