The Food-effect on Alectinib Pharmacokinetics

NSCLC Clinical Trial

Official title: The Food-effect of a Standardized Dutch Breakfast on the Pharmacokinetics of Oral Alectinib (Alecensa®) Using a Stable Isotopically Labelled Microtracer Approach

Status Enrolling by invitation

Clinical Trial Summary

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.

Clinical Trial Description

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. ;

Related Conditions & MeSH terms

• NSCLC

• NCT number: NCT05710133
• Study type: Interventional
• Source: The Netherlands Cancer Institute
• Status: Enrolling by invitation
• Phase: N/A
• Start date: February 1, 2024
• Completion date: March 1, 2025