Practical Considerations for the Design, Conduct, and Reporting of Clinical Pharmacokinetic Drug–Drug Interaction Studies in Drug Development

Abstract

Clinical pharmacokinetic drug–drug interaction (PK‐DDI) studies are frequently required in drug development when metabolizing enzymes and transporters determine pharmacokinetics. Drugs can be victims, perpetrators, or victims and perpetrators, of PK‐DDIs, so the clinical consequences of these interactions, particularly the risks of severe adverse effects and therapeutic failures leading to poor clinical outcomes, must be well understood prior to regulatory filings. In this Commentary, background information on PK‐DDIs is summarized to the point in drug development where the decision is made to conduct a human study. Practical considerations for the design and conduct of clinical PK‐DDI studies are then addressed sequentially, including guidance about study populations, the selection of probe drugs, their doses and durations, suitable study designs, the contentious issues with inclusion and exclusion criteria, which endpoints are the most important, and samples sizes and power estimates. Guidance on how results should be reported is given, including clinical study reports and scientific literature. Although intended primarily for the pharmaceutical industry, the key points apply across all sectors of drug development and are best considered together with regulatory guidelines on drug interaction studies.