Ji, Yan, Tan, Eugene, Hengelage, Thomas, Quinlan, Michelle and Hendriks, Bart (2023) Roadmap for exploratory food effect assessment in early clinical development for oncology drugs - literature and Novartis experience. Clinical pharmacology and therapeutics.

Abstract

Instructions for administration with regard to food are a key aspect of how patients experience oral drugs. Through potential effects on pharmacokinetics, the food condition can influence safety and efficacy, and thereby is one of many dimensions of dose optimization. Regulatory guidance from major health authorities advocates for the early investigation of food effect (FE) in clinical development. In oncology, exploratory food effect (eFE) evaluation is often incorporated into the first-in-human (FIH) studies in patients to inform food condition of later clinical studies. The design aspects of such exploratory assessments are generally under-reported and barely described, but on the other hand, complex, due to uniqueness of FIH study design and drug development process in oncology. Herein, we provide an outline for setting initial food conditions and review literature of eFE assessments in early phase oncology studies in patients. Further, we reviewed the Novartis experience in the design, execution, and impact of eFE in FIH oncology studies of 2014 - 2021. Based on literature examples and our own experience, we propose a roadmap for eFE assessment in early clinical drug development for oncology drugs, including a framework for common study design options, with a focus on study and patient-level timing for typical scenarios to enable either intra or inter-patient pharmacokinetic comparisons with or without food, as well as a spectrum of decision-making factors spanning from clinical development strategy, FIH study design, to compound specific features, which should be evaluated to drive the design and implementation of eFE assessment.

Item Type:	Article
Date Deposited:	14 Nov 2023 00:45
Last Modified:	14 Nov 2023 00:45
URI:	https://oak.novartis.com/id/eprint/49260