An Open-Label, Fixed-Sequence Study to Evaluate the Effect of Multiple Doses of LOXO-292 on the Single Dose Pharmacokinetics of Midazolam in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Midazolam and Its Metabolite 1-hydroxymidazolam (1-OH-midazolam)
研究概览
简要总结
The main purpose of this study is to assess the effect of selpercatinib on how fast midazolam gets into the blood stream and how long it takes the body to remove it when administered in healthy participants. Information about safety and tolerability will be collected. The study will last up to about 6 weeks, inclusive of screening period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- None
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
- 未提供
排除标准
- •Are currently participating in or completed a clinical trial within the last 30 days or any other type of medical research judged to be incompatible with this study
- •Have previously participated or withdrawn from this study
- •Have or used to have health problems or laboratory test results or ECG readings that, in the opinion of the doctor, could make it unsafe to participate, or could interfere with understanding the results of the study
- •Had blood loss of more than 500 milliliters (mL) within the previous 30 days of study screening
- •Require treatment with inducers or inhibitors of cytochrome P450 (CYP) CYP3A within 14 days before the first dose of study drug through the end of Period 2
研究组 & 干预措施
Period 1: Midazolam
- Day 1: Participants received single oral dose of 2 milligram (mg) midazolam syrup.
干预措施: Midazolam (Drug)
Period 2: Selpercatinib + Midazolam
- Day 1 to Day 9: Participants received 160 mg Selpercatinib capsules twice daily (BID).
- Day 10: Participant received 160 mg Selpercatinib capsules BID co-administered with a single oral dose of 2 mg midazolam syrup on the morning of Day 10.
干预措施: Midazolam (Drug)
Period 2: Selpercatinib + Midazolam
- Day 1 to Day 9: Participants received 160 mg Selpercatinib capsules twice daily (BID).
- Day 10: Participant received 160 mg Selpercatinib capsules BID co-administered with a single oral dose of 2 mg midazolam syrup on the morning of Day 10.
干预措施: Selpercatinib (Drug)
结局指标
主要结局
Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Midazolam and Its Metabolite 1-hydroxymidazolam (1-OH-midazolam)
时间窗: Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)
PK: PK: AUC0-t of midazolam and its metabolite 1-OH-midazolam was reported.
PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Midazolam and Its Metabolite 1-OH-midazolam
时间窗: Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)
PK: PK: AUC0-inf of midazolam and its metabolite 1-OH-midazolam was reported.
PK: Time to Reach Maximum Observed Concentration (Tmax) of Midazolam and Its Metabolite 1-OH-midazolam
时间窗: Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)
PK: Tmax of midazolam and its metabolite 1-OH-midazolam was reported.
PK: Apparent Terminal Elimination Rate Constant (Kel) of Midazolam and Its Metabolite 1-OH-midazolam
时间窗: Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)
PK: Kel of midazolam and its metabolite 1-OH-midazolam was reported.
PK: Apparent Terminal Elimination Half-life (t½) of Midazolam and Its Metabolite 1-OH-midazolam
时间窗: Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)
PK: t½ of midazolam and its metabolite 1-OH-midazolam was reported.
PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Midazolam
时间窗: Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)
PK: CL/F of midazolam was reported.
PK: Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of Midazolam
时间窗: Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)
PK: Vz/F of midazolam was reported.
PK: Percent of AUC0-inf Extrapolated (AUC%Extrap) of Midazolam and Its Metabolite 1-OH-midazolam
时间窗: Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)
PK: PK: AUC%extrap of midazolam and its metabolite 1-OH-midazolam was reported.
PK: Maximum Observed Concentration (Cmax) of Midazolam and Its Metabolite 1-OH-midazolam
时间窗: Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)
PK: Cmax of midazolam and its metabolite 1-OH-midazolam was reported.
次要结局
- PK: Area Under the Concentration-time Curve, From Time 0 to the 12 Hour (AUC0-12) of Selpercatinib(Period 2: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose))
- PK: Area Under the Concentration-time Curve During a Dosing Interval (Tau) at Steady State (AUCtau) of Selpercatinib(Period 2: Day 9 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose); Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose))
- PK: Concentration Observed at the End of the Dosing Interval (Ctrough) of Selpercatinib(Period 2: Predose at Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9)
- PK: Maximum Observed Concentration (Cmax) of Selpercatinib(Period 2: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose))
- PK: Maximum Observed Concentration at Steady-state (Cmax,ss) of Selpercatinib(Period 2: Day 9 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose); Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose))
- PK: Time to Reach Maximum Observed Concentration at Steady-state (Tmax,ss) of Selpercatinib(Period 2: Day 9 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose); Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose))
- PK: Time to Reach Maximum Observed Concentration (Tmax) of Selpercatinib(Period 2: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose))
- PK: Apparent Total Plasma Clearance at Steady State After Oral/Extravascular Administration (CL,ss/F) of Selpercatinib(Period 2: Day 9 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose); Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose))