1. Introduction

(This section is organised in the form of a book, please follow the blue arrows to navigate through the book or by following the navigation panel on the right side of the page.)

After the successful completion of Phase I, the experimental medicine is next tested for efficacy (and safety) in Phase II clinical trials. If a significant portion of patients (afflicted with the disease or condition for which the medicine is developed) respond to the treatment, the treatment is judged to work or be ‘active’.

Phase II usually starts with studies in which the primary objective is to explore therapeutic efficacy and safety in patients. Patients are selected by strict selection (inclusion) criteria, leading to a relatively homogenous population, this is done in order to facilitate the interpretation of study results. Phase II studies typically involve:

  • Determining the dose(s) and regimen for Phase III trials - often dose finding designs are utilised to give an early estimate of dose response for a pursued indication. Confirmatory dose response studies may be conducted in Phase II or left for Phase III.

  • Exploratory analysis of multiple endpoints.

  • Exploratory analysis of therapeutic regimens including concomitant medications (medicines which are used at the same time or shortly after another).

  • Exploratory analysis of target populations (e.g. mild versus severe disease) for further study in Phase II or III.
Often surrogate endpoints are used (rather than clinical endpoints, the use of which occurs later) since the objective is to show some sign of efficacy (Proof of Concept (PoC)) rather than demonstrate efficacy as is done in confirmatory trials (Phase III). Phase II are typically fairly short, lasting several weeks (or months).

The objectives of the Phase II development are:

  • To explore therapeutic efficacy (and safety) in patients
    • Proof of concept (PoC): to determine the existence of activity or ‘response’ (often using surrogate endpoints) of a new treatment in a particular patient population.

  • To determine the dose(s) and regimen (schedule) for Phase III trials
    • Dose-range exploration: Finding the lowest effective dose and the optimal dose.

  • To explore potential trial endpoints, concomitant medications, and target populations (e.g. age, gender, disease stage/degree), and cumulative effects for subsequent studies, and provide the basis for confirmatory trial design.
Phase II studies are performed on large groups of patients (~100-500) usually seeing more than 30 patients per treatment group. When the development of a new medicine fails, it is often during phase II studies when the medicine is discovered not to work as expected, or to have unforeseen toxic effects in patients.

The outcomes of PoC should unambiguously be associated with clinical improvement. These outcomes and results must be considered which making a ‘go/no-go’ decision to progress to Phase III development.