Phase I clinical trials mark the first time a potential new therapy or drug candidate is administered to human volunteers. Whereas preclinical studies in cells and animals reveal preliminary safety and efficacy, Phase I transitions into humans with the core aim of establishing an initial safety profile. These trials typically enroll between 20 and 80 healthy participants—though in oncology or other high-risk areas, patients with the target disease may be enrolled directly.
Key Objectives
- Safety and Tolerability:
- Identify any adverse events (AEs) and dose-limiting toxicities (DLTs).
- Document the maximum tolerated dose (MTD) to guide dosing in later phases.
- Pharmacokinetics (PK):
- Measure how the drug is absorbed, distributed, metabolized, and excreted (ADME).
- Determine parameters such as C_max (peak concentration), T_max (time to peak), and half-life (t½).
- Pharmacodynamics (PD):
- Assess biological effects of the drug on target markers or pathways.
- Correlate drug concentration with observed pharmacological response.
Design Elements
- Cohort Escalation: Small groups receive increasing doses in a stepwise fashion. Decisions to escalate or halt are based on real-time safety reviews.
- Sentinel Dosing: Often the first two subjects in a cohort are dosed and observed before full cohort dosing begins.
- Bridging Studies: When moving from healthy volunteers to patient populations, additional sub-studies ensure safety in the intended disease context.
Ethical and Regulatory Oversight
- Institutional Review Boards (IRBs) or Ethics Committees must approve the protocol and informed-consent documents.
- Data Safety Monitoring Boards (DSMBs) may convene for independent safety reviews, especially in higher-risk interventions.
- Adherence to Good Clinical Practice (GCP) guidelines and local regulations ensures participant protection and data integrity.
Why It Matters
Phase I data form the cornerstone of the entire development pathway. A clear understanding of safety margins, PK/PD relationships, and dose tolerability not only protects participants but also de-risks the investment in later, much larger and cost-intensive Phase II and III trials.