Introduction
Phase II (therapeutic exploration) is the first use of the drug in patients with the target disease. It asks whether the drug works at all, and at what dose.
Target population
- About 100–500 patients (ranges of 50–500 are quoted) with the disease, selected by narrow, strict criteria: few co-morbidities and other drugs, so that the drug effect is clear.
- Single-centre or multi-centre.
Aims
- Initial evidence of efficacy (proof of concept).
- Safety and tolerability in patients (short-term adverse reactions).
- Dose–response: choose the dose(s) and regimen for phase III.
- PK and PD in patients; identify subgroups and endpoints for phase III.
Design
- Endpoints are often surrogate markers that respond quickly (blood pressure, HbA1c, viral load, tumour shrinkage) rather than hard outcomes (death, stroke).
- In oncology, single-arm trials measuring response rate (e.g. Simon two-stage design) are common.
- Short duration (weeks to months).
Significance
Phase II is where most new drugs fail, mainly for lack of efficacy or safety problems. A well-chosen dose in phase IIb is essential: a wrong dose can doom an otherwise useful drug in phase III.
Phase II is the first test in patients: proof of concept and the dose for phase III, usually in a randomised, double-blind, placebo-controlled design.