A Phase I, Open-Label, Non-Randomised, Multicentre Study to Assess the Effect of AZD9291 on the Pharmacokinetics of Simvastatin (a Sensitive CYP3A4 Substrate) in Patients With EGFRm Positive NSCLC Whose Disease Has Progressed on an EGFR TKI
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Cmax of Simvastatin
研究概览
简要总结
This is a Phase I, open-label, 2-part study in patients with a confirmed diagnosis of epidermal growth factor receptor (EGFR) mutation positive (EGFRm+) non-small cell lung cancer (NSCLC), who have progressed following prior therapy with an approved EGFR tyrosine kinase inhibitor (TKI) agent.
Part A will assess the effect of AZD9291 on the pharmacokinetic (PK) parameters of simvastatin and simvastatin acid, following multiple oral dosing of AZD9291 in a fasted state.
Part B will allow patients further access to AZD9291 after the PK phase (Part A) and will provide for additional safety data collection. All patients from Part A who completed treatment may continue to receive AZD9291 80 mg once daily until: disease progression; they are no longer deriving clinical benefit; or any other reason.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 主要目的
- Treatment
- 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
AZD9291 and simvastatin
Sequential treatments of simvastatin alone followed by AZD9291 alone, followed by simvastatin + AZD9291.
干预措施: Pharmacokinetic sampling - AZD9291 (Procedure)
AZD9291 and simvastatin
Sequential treatments of simvastatin alone followed by AZD9291 alone, followed by simvastatin + AZD9291.
干预措施: Simvastatin (Drug)
AZD9291 and simvastatin
Sequential treatments of simvastatin alone followed by AZD9291 alone, followed by simvastatin + AZD9291.
干预措施: AZD9291 tablet dosing (Drug)
AZD9291 and simvastatin
Sequential treatments of simvastatin alone followed by AZD9291 alone, followed by simvastatin + AZD9291.
干预措施: Pharmacokinetic sampling - simvastatin (Procedure)
AZD9291 and simvastatin
Sequential treatments of simvastatin alone followed by AZD9291 alone, followed by simvastatin + AZD9291.
干预措施: Pharmacokinetic sampling - AZ5140 and AZ7550 (Procedure)
结局指标
主要结局
Cmax of Simvastatin
时间窗: Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part A
Pharmacokinetics of simvastatin by assessment of maximum plasma simvastatin concentration
AUC of Simvastatin
时间窗: Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part A
Pharmacokinetics of simvastatin by assessment of area under the plasma concentration time curve from zero to infinity
次要结局
- Tmax of Simvastatin and Simvastatin Acid(Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part A)
- CL/F of Simvastatin(Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part A)
- Cmax of Simvastatin Acid(Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part A)
- AUC of Simvastatin Acid(Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part A)
- AUC(0-t) of Simvastatin and Simvastatin Acid(Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part A)