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.
- Strategic planning for…
- Proper timing to execute a food effect study
- determination if a preliminary food effect assessment should be done early in development
- Full clinical protocol development from clinical pharmacology experts
- Clinical trial design
- Power calculation for determination sample size for food effect study
- PK sampling schedule evaluation
- Topline assessment of food effect within 24 hours
- Full PK analysis (PK parameters) conducted in WinNonlin
- Full or abbreviated PK report
- Clinical study reports (CSRs) – with integrated PK data
- Investigator Brochure (IB) updates to clinical pharmacology and PK data
- FDA meetings or EMA meetings: Expert clinical pharmacology representation at regulatory meetings (including Briefing packet preparation)
- Interpretation of PK data to enable next steps in the development program
- Incorporation of data into model based drug development to allow for better decision making.
- Impact of study results on other planned clinical studies
- Although Nuventra does not enroll or dose subjects in clinical trials, our high level of experience with designing, executing and analyzing data from clinical pharmacology & PK/PD studies makes us the best option for clients needing advice in this area of drug development.
Brief 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.
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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.
Let Nuventra’s clinical pharmacology consultants, pharmacokineticists, and drug development experts help intelligently integrate this study into your overall development efforts. Click here for a Clinical Pharmacology Plan.
Contact us or request a quote to help interpret the guidance to industry and with your drug development needs for this type of clinical pharmacology investigation.