Food can change the rate of absorption and pharmacokinetics of drugs administered orally and the FDA requires the determination of a food effect for such drugs. A food effect is defined by pharmacokinetic parameters where a reduced Cmax and delayed Tmax observed under fed conditions relative to fasted conditions are characteristic of an effect. Since PK is crucial to the success of this type of study, engaging a pharmacokineticist during protocol development to devise a proper PK blood sampling schedule is important as consideration must be given to the possibility that food can alter the time course of plasma drug concentrations. A full PK profile must be generated based on an adequate sampling schedule or the study may fail to meet its objective of determining a food effect.
Scientific & PK Considerations for Food Effect Studies
The FDA’s guidance to industry recommends that food effect studies be designed as randomized, balanced, single-dose, two-treatment (fed vs. fasting), two-period, two-sequence crossover in healthy volunteers. For the fed period, a high-calorie and high-fat meal is given to the subject following an overnight fast of at least 10 hours and study drug is administered 30 minutes after the subjects begins consuming the meal. The FDA’s industry guidance recommends a formal powered study with a minimum of 12 subjects completing the study and statistical assessments based on key pharmacokinetic parameter (Cmax and AUC). Nuventra has a robust food effect protocol template based on the FDA guidance to industry.
As described above, a crucial step in planning this type of study is enlisting a pharmacokineticist during protocol development to devise a proper PK blood sampling schedule and after database lock to conduct a proper analysis of PK parameters.
When to Execute Food Effect Studies in Development Programs
Bioavailability studies conducted under fed and fasted conditions are required prior to NDA submission to determine if a food effect exists. However, a food effect has implications for designing other investigational studies in support of an NDA so the timing of obtaining food effect information is important. While a formally powered study is needed for the NDA, in many instances a preliminary assessment of the food effect can be obtained very early in development as an additional cohort in single ascending dose or multiple ascending dose studies. This preliminary assessment does not have to be formally powered to provide insight into the potential for a food effect and could be a valuable tool for strategic planning of clinical studies in a development plan.
Learn more by reading FDA’s Guidance “Food-Effect Bioavailability and Fed Bioequivalence Studies.”