A Phase 1, Open-label, Two-part Study to Investigate the Absorption, Metabolism, and Excretion, and the Absolute Bioavailability of [14C]-LOXO-292 in Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- PK: AUClast of [14C] Selpercatinib in Plasma and Whole Blood (Part 1) for Total Radioactivity
研究概览
简要总结
The main purpose of this study is to compare the amount of selpercatinib that gets into the blood stream and how long it takes the body to get rid of it and also to assess the pharmacokinetics (PK), metabolism, and routes and extent of elimination of selpercatinib in healthy male participants. The study will last up to 59 days (Part 1) or 46 days (Part 2) including screening and 7-day safety follow-up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- Male
- 接受健康志愿者
- 是
入选标准
- •Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kilograms per meter squared (kg/m²)
- •Have normal blood pressure, pulse rate, electrocardiogram (ECG), and blood and urine laboratory test results that are acceptable for the study
- •Participants will be surgically sterile for at least 90 days prior to Check in or, when sexually active with female partners of childbearing potential, will agree to use effective contraception methods or abstain from sexual intercourse from the time of first dose through 90 days after study drug administration
排除标准
- •Participation in any other radiolabeled investigational study drug trial within 12 months prior to Check-in
- •Exposure to significant radiation (eg, serial x-ray or computed tomography scans, barium meal, current employment in a job requiring radiation exposure monitoring) within 12 months prior to Check-in
- •Use or intention to use any medications/products known strong inducers or inhibitors of Cytochrome P450 3A4 enzymes, including St. John's wort, within 30 days prior to Check-in, unless deemed acceptable by the Investigator (or designee)
研究组 & 干预措施
Carbon-14-labelled [14C]-Selpercatinib - Part 1
Participants received a single oral dose of 165 milligram (mg) of [14C]-Selpercatinib (containing approximately 40 µCi).
干预措施: [14C]-Selpercatinib (Drug)
Selpercatinib and [14C]-Selpercatinib - Part 2
Participants received a single oral dose of 160 mg Selpercatinib followed by single dose of <100 µg of [14C]-Selpercatinib (containing approximately 1 µCi) administered intravenously (IV).
干预措施: Selpercatinib (Drug)
Selpercatinib and [14C]-Selpercatinib - Part 2
Participants received a single oral dose of 160 mg Selpercatinib followed by single dose of <100 µg of [14C]-Selpercatinib (containing approximately 1 µCi) administered intravenously (IV).
干预措施: [14C]-Selpercatinib (Drug)
结局指标
主要结局
PK: AUClast of [14C] Selpercatinib in Plasma and Whole Blood (Part 1) for Total Radioactivity
时间窗: PK: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: AUClast of \[14C\] Selpercatinib in plasma and whole blood
PK: Apparent First-order Terminal Elimination Half-life (t½) of Selpercatinib in Plasma (Part 1)
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: t½ of Selpercatinib in plasma
PK: t½ of [14C] Selpercatinib in Plasma and Whole Blood (Part 1) for Total Radioactivity
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: t½ of \[14C\] Selpercatinib in plasma and whole blood
PK: Apparent Systemic Clearance (CL/F) of Selpercatinibin Plasma (Part 1)
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: CL/F of Selpercatinib in plasma
PK: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Selpercatinib in Plasma (Part 1)
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Vz/F of Selpercatinib in plasma
PK: Plasma Selpercatinib/Total Radioactivity AUC0-24 Ratio (Part 1)
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose
PK: AUC0-24 of Selpercatinib in plasma/AUC0-24 of total radioactivity in plasma
PK: Blood/Plasma Total Radioactivity AUC0-24 Ratio (Part 1)
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose
PK: AUC0-24 of total radioactivity in whole blood/AUC0-24 of total radioactivity in whole blood
PK: AUClast of Selpercatinib in Plasma (Part 2)
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: AUClast of Selpercatinib in plasma
PK: AUClast of [14C] Selpercatinib in Plasma (Part 2)
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: AUClast of \[14C\] Selpercatinib in plasma
PK: AUC0-inf of Selpercatinib in Plasma (Part 2)
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: AUC0-inf of Selpercatinib in plasma
PK: AUC0-inf of [14C] Selpercatinib in Plasma (Part 2)
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: AUC0-inf of \[14C\] Selpercatinib in plasma
PK: Cmax of Selpercatinib in Plasma (Part 2)
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Cmax of Selpercatinib in plasma
PK: Cmax of [14C] Selpercatinib in Plasma (Part 2)
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Cmax of \[14C\] Selpercatinib in plasma
PK: Tmax of Selpercatinib in Plasma (Part 2)
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Tmax of Selpercatinib in plasma
PK: Tmax of [14C] Selpercatinib in Plasma (Part 2)
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Tmax of \[14C\] Selpercatinib in plasma
PK: t½ of Selpercatinib in Plasma (Part 2)
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: t½ of Selpercatinib in plasma
PK: t½ of [14C] Selpercatinib in Plasma (Part 2)
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: t½ of \[14C\] Selpercatinib in plasma
PK: CL/F of Selpercatinib in Plasma (Part 2)
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: CL/F of Selpercatinib in plasma
PK: Systemic Clearance (CL) of [14C] Selpercatinib in Plasma (Part 2)
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: CL of \[14C\] Selpercatinib in plasma
PK: Vz/F of Selpercatinib in Plasma (Part 2)
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Vz/F of Selpercatinib in plasma
PK: Volume of Distribution During the Terminal Phase (Vz) of [14C] Selpercatinib in Plasma (Part 2)
时间窗: Pre-dose up to 168 hour post-dose
PK: Vz of \[14C\] Selpercatinib in plasma
PK: Volume of Distribution at Steady State (Vss) of [14C] Selpercatinib in Plasma (Part 2)
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Vss of \[14C\] Selpercatinib in plasma
Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Selpercatinib in Plasma (Part 1)
时间窗: PK: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: AUClast of Selpercatinib in plasma
PK: Area Under the Concentration-time Curve, From Time 0 Extrapolated to Infinity (AUC0-inf) of Selpercatinib in Plasma (Part 1)
时间窗: PK: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: AUC0-inf of Selpercatinib in plasma
PK: AUC0-inf of [14C] Selpercatinib in Plasma and Whole Blood (Part 1) for Total Radioactivity
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: AUC0-inf of \[14C\] Selpercatinib in plasma and whole blood
PK: Area Under the Concentration-time Curve, From Time 0 to Hour 24 (AUC0-24) of Selpercatinib in Plasma (Part 1)
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose
PK: AUC0-24 of Selpercatinib in plasma
PK: (AUC0-24) of [14C] Selpercatinib in Plasma and Whole Blood (Part 1) for Total Radioactivity
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose
PK: AUC0-24 of \[14C\] Selpercatinib in plasma and whole blood
PK: Maximum Observed Concentration (Cmax) of Selpercatinib in Plasma (Part 1)
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Cmax of Selpercatinib in plasma
PK: Cmax of [14C] Selpercatinib in Plasma and Whole Blood (Part 1) for Total Radioactivity
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Cmax of \[14C\] Selpercatinib in plasma and whole blood
PK: Time to Reach Cmax (Tmax) of Selpercatinib in Plasma (Part 1)
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Tmax of Selpercatinib in plasma
PK: Tmax of [14C] Selpercatinib in Plasma and Whole Blood (Part 1) for Total Radioactivity
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
PK: Tmax of \[14C\] Selpercatinib in plasma and whole blood
PK: Absolute Bioavailability (F) of Selpercatinib in Plasma (Part 2)
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose
Absolute bioavailability was determined by comparing the plasma exposure of LOXO-292 following oral dosing with the plasma exposure of \[14C\]-LOXO-292 following IV dosing.
次要结局
未报告次要终点