Phase I Clinical Trial
The first stage of human testing, primarily assessing safety, tolerability, pharmacokinetics, and appropriate dosing in 20-100 participants. Phase I trials establish the maximum tolerated dose and characterise how the body handles the drug. Success leads to Phase II.
Technical Context
Phase I designs include: single ascending dose (SAD) — small groups receive increasing single doses with safety monitoring between cohorts; multiple ascending dose (MAD) — groups receive repeated doses at each level to assess accumulation and steady-state PK; and food effect studies (assessing whether food alters absorption). First-in-human (FIH) starting dose is typically calculated from preclinical NOAEL using allometric scaling and a safety factor (usually 1/10th of the human equivalent dose of the animal NOAEL). For peptide drugs, Phase I establishes: maximum tolerated dose, dose-limiting toxicities, pharmacokinetic profile (Cmax, AUC, t1/2, CL, Vd), preliminary pharmacodynamic markers, and immunogenicity. Healthy volunteer studies are typical except for cytotoxic peptides (e.g. proteasome inhibitors) where Phase I enrols patients.