Phase 1 studies conducted in parallel with phase 2

Phase 1 studies conducted in parallel with phase 2 are intended to evaluate important physiological and other factors that might affect the efficacy or safety of an investigational drug (covariates). Results will inform dosing and exclusion criteria for a phase 3 trial.

Studies may explore the impact of renal impairment and/or hepatic impairment (depending on how a drug is metabolized and cleared from the body).

Drug–drug interaction studies are also conducted to assess whether administration of a drug will affect the metabolism and therefore efficacy or safety of another drug given at the same time. This is particularly important when a new drug is likely to be used in a population where use of another a drug is common, and when a new drug is known to induce responses that could affect the metabolism of another drug.

The indication being targeted in phase 3 studies may also affect the need for additional studies. For example, pharmacokinetic studies of epithelial lining fluid (ELF) may be important for pneumonia treatments – providing evidence of the extent to which a drug reaches the site of infection.

Regulatory guidance or precedent should guide the design and conduct of these studies.

Guidance

Guidance is available from both the FDA and the EMA on drug–drug interaction studies.

Guidance is also available specific to renal impairment and hepatic impairment.