The Food-effect of a Standardized Dutch Breakfast on the Pharmacokinetics of Oral Alectinib (Alecensa®) Using a Stable Isotopically Labelled Microtracer Approach
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- food-effect on alectinib
研究概览
简要总结
The goal of this food-effect study on Alectinib pharmacokinetics is to learn about the food effect of alectinib. The main question aims to answer is:
• To determine the food-effect of a standardized Dutch breakfast on the pharmacokinetics of oral alectinib (Alecensa®), especially Peak Plasma Concentration (Cmax), Area under the plasma concentration versus time curve (AUC) and relative bioavailability, at steady state using a stable isotopically labelled microtracer approach.
Participants will take alectinib-d6 (microtracer) with and without food on different days.
详细描述
The aim of this study is to determine the food-effect of a standardized Dutch breakfast on the pharmacokinetics of alectinib. Despite the fact that three studies have reported a food-effect on alectinib pharmacokinetics, it is still unclear what the food-effect is on alectinib exposure in the daily lives of patients. It is important to understand this effect due the high inter- and intra-individual variability observed in alectinib exposure as well as the observed exposure-response relationship. Food might be a strategy to increase exposure without dose increase or reduce intra-individual variability.
A conventional, cross-over, food-effect study requires the participating patients to administer the investigational drug with and without food over several days until steady-state is reached (approximately 5 times the half-life of the respective drug). When steady-state is reached, blood samples will be collected for the determination of exposure of the investigational drug. However, this study design is inappropriate for the determination of the food-effect of alectinib due to possibly underexposure. A previously reported exposure-response analysis reported significantly decreased survival for NSCLC patients with an alectinib trough plasma concentrations (Ctrough) <435 ng/mL. Clinical trial simulations demonstrated that 55.5% of patients will have Ctrough below the target when alectinib is administered under fasting conditions assuming a food-effect of 40%.
A microtracer approach was chosen to determine the food-effect on alectinib pharmacokinetics without influencing the therapeutic treatment. A microtracer is a 100 µg dose of a stable isotopically labelled (SIL) drug. These microtracers have been used for the determination of absolute food-effect. Due to the mass difference between the therapeutic administered drug and the microtracer, the concentrations of both compounds can be simultaneously quantified in the same sample.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Currently treated with alectinib for NSCLC or other oncological indications;
- •On alectinib treatment at a stable dose of 600 mg twice daily (≥ 7 days) according to standard of care
- •Age ≥ 18 years;
- •Able and willing to give written informed consent;
- •world health organization (WHO) performance status of 0,1 or 2;
- •Able and willing to undergo blood sampling for pharmacokinetic analysis;
- •Able and willing to get one intravenous line for pharmacokinetic sampling
- •Able and willing to comply with study restrictions and to remain at the study center for the required duration.
- •Able and willing to undergo the defined food interventions
排除标准
- •Any treatment with investigational drugs (alectinib-d6) within 30 days or 5 half-lives prior to receiving the investigational treatment;
- •Any treatment with inhibitors of CYP3A4 (e.g. boceprevir, clarithromycin, erythromycin, indinavir, itraconazole, ketoconazole, ritonavir and voriconazole), inhibitors of Pgp (e.g. cyclosporine, kinidine, and verapamil), inhibitors of breast cancer resistance protein (BCRP) (e.g. lapatinib), inductors of CYP3A4, Pgp or BCRP;
- •Patients suffering from any known disease or dysfunction that might influence the dissolution and/or absorption of alectinib (e.g. inflammatory bowel disease, gastric bypass).
研究组 & 干预措施
alectinib-d6
Patients will receive one single dose of alectinib-d6 (100 µg) orally on day 1 and 9.
干预措施: food (Other)
alectinib-d6
Patients will receive one single dose of alectinib-d6 (100 µg) orally on day 1 and 9.
干预措施: fast (Other)
结局指标
主要结局
food-effect on alectinib
时间窗: 10 days
To determine the food-effect of a standardised Dutch breakfast on the pharmacokinetics (Cmax) of oral alectinib (Alecensa®), at steady state using a stable isotopically labelled microtracer approach.
次要结局
未报告次要终点