An Open-label PET Study to Determine Brain Exposure of Osimertinib After IV Microdose Administration of [11C]Osimertinib and Therapeutic Oral Doses of Osimertinib to Patients With EGFR Mutated NSCLC With Brain Metastases
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Maximum Concentration of Percent of Injected Dose in the Whole Brain (Cmax, %ID Brain) of [11C]Osimertinib
研究概览
简要总结
This is an open-label, single centre, Phase I study to determine the brain exposure of [11C]osimertinib in patients with EGFRm NSCLC with brain metastases.
详细描述
A Single-centre, Open-label, PET imaging and Pharmacokinetic Study of IV Administered [11C]osimertinib in EGFRm Non-small cell lung cancer patients with brain metastases. The study will consist of 2 phases, an imaging phase and a continuous access phase.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
[11C]osimertinib + oral osimertinib
IV microdose administrations of [11C]osimertinib co-administered with 80 mg daily oral osimertinib.
干预措施: Osimertinib (Drug)
[11C]osimertinib + oral osimertinib
IV microdose administrations of [11C]osimertinib co-administered with 80 mg daily oral osimertinib.
干预措施: [11C]osimertinib (Drug)
结局指标
主要结局
Maximum Concentration of Percent of Injected Dose in the Whole Brain (Cmax, %ID Brain) of [11C]Osimertinib
时间窗: Day 1, Day 2 (or up to Day 8) and Day 25
During the PET examination time, a series of arterial blood samples were taken to measure Cmax, %ID brain of \[11C\]osimertinib.
Time of Maximum Radioactivity Concentration in the Brain (Tmax, Brain) of [11C]Osimertinib
时间窗: Day 1, Day 2 (or up to Day 8) and Day 25
The Tmax, brain was determined directly from the observed concentration versus time data.
Maximum Concentration of Brain Standardized Uptake Value (Cmax, SUV Brain) of [11C]Osimertinib
时间窗: Day 1, Day 2 (or up to Day 8) and Day 25
During the PET examination time, a series of arterial blood samples were taken to measure Cmax, SUV brain of \[11C\]osimertinib.
Brain to Plasma Partition Coefficient (Kp) of [11C]Osimertinib
时间窗: Day 1, Day 2 (or up to Day 8) and Day 25
The Kp was defined as ratio of radiolabeled drug in brain to that in plasma calculated as area under the brain radioactivity concentration-time curve between 0 and 90 minutes/area under the plasma radioactivity concentration-time curve between 0 and 90 minutes.
次要结局
- Maximum Concentration at Steady State (Css,Max) of Osimertinib and Metabolite AZ5104(Pre-dose and 2, 4 and 7.5 hours postdose on Day 25)
- Area Under the Concentration-Time Curve at Steady State (AUCss) of Osimertinib and Metabolite AZ5104(Pre-dose and 2, 4 and 7.5 hours postdose on Day 25)
- Time of Maximum Drug Concentration at Steady State (Tss,Max) of Osimertinib and Metabolite AZ5104(Pre-dose and 2, 4 and 7.5 hours postdose on Day 25)
- Metabolite to Parent Ratio of AUCss(Pre-dose and 2, 4 and 7.5 hours postdose on Day 25)
- Metabolite to Parent Ratio of Css,Max(Pre-dose and 2, 4 and 7.5 hours postdose on Day 25)