Phase II Trials

-D.Saikrishna

Introduction
Phase II includes the early controlled clinical studies conducted to obtain some preliminary data on the effectiveness of the drug for a particular indication in patients with the disease or condition

 This phase of testing also helps determine the common short-term side effects and risks associated with the drug. Phase II studies are typically wellcontrolled, closely monitored, and conducted in a relatively small number of patients, usually involving several hundreds of people.

Objective
Evaluate the effectiveness of a drug for a particular indication or indications in patients with the condition under study Determine common short term side effects Risks associated with the drug

Objectives
Studies in Phase II should be conducted in a group of patients who are selected by relatively narrow criteria leading to a relatively homogeneous population

Objectives
Theses studies should be closely monitored An important goal for this phase is to determine the dose (s) and regimen for phase III trials. Doses used in Phase II are usually (but not always) less than the highest dose used in Phase I.

Objectives
Additional objectives can include evaluation of potential study endpoints, therapeutic regimens (including concomitant medications) and target populations (e.g mild v/s severe disease) for further studies in Phase II and III. Theses objectives may be served by exploratory analysis, examining subsets of data and by including multiple endpoints in trials.

Regulation
If the application s for conduct of clinical trials as a part of multinational clinical development of the drug, the number of sites and the patients as well as the justification for undertaking such trials in India shall be provided to the Licensing Authority.

Design
Single-arm Phase II trial Each patients outcome is recorded and noted if the desirable response to therapy has been achived. If the observed response rate is sufficiently high, this is used as the rationale to conduct a confirmatory Phase III trial.

Types
Sometimes divided into -Phase IIA -Phase IIB Phase IIA is specifically designed to assess dosing requirements (how much drug should be given) Phase IIB is specifically designes to study efficacy [how well the drug works at the prescribed dose(s)] Some trials combine Phase I and Phase II, and test both efficacy and toxicity.

Dose-Ranging Studies
Sufficient dose levels in 1 or more studies to establish: Ineffective dose (may come from Phase I) Lowest effective dose Maximally effective dose Maximally tolerated dose Separate dose ranging may be needed for elderly or children

Pharmacokinetic Studies
Single dose pharmacokinetics Multiple dose pharmacokinetics (steady state) Population pharmacokinetics Special population pharmacokinetics Elderly Children Organ impairment Fast/slow metabolizes Metabolism study

Example-1
Phase II Trial of Erlotinib in Advanced Pancreatic Cancer

 Sponsor: University Health Network, Toronto Collaborator: OSI Pharmaceuticals Study Type: Interventional Study Design: Allocation: Non-Randomized Primary Purpose: Treatment

Example-1
Primary objective: To determine the efficacy of erlotinib, as measured by the rate of disease control, in patients with unresectable, locally advanced or metastatic pancreatic adenocarcinoma.

Example-1
The presence of the erlotinib-induced rash is associated with improved survival in Phase II and III trials of diverse tumor types, and is associated with higher steady state concentrations of erlotinib This Phase II trial aims to dertimine the safety and efficacy of erlotinib in patients with advanced pancreatic cancer who have previously been treated with up to one prior line of gemcitabine based chemotherapy for advanced disease. In addition, the feasibility and activity of dose escalation of erlotinib in patients who do not develop a rash is also evaluated

Australian government Department of health and ageing http://www.cc.nih.gov/training/training/principles/slides/Population08-09Text.pdf http://www.fda.gov/downloads/ScienceResearch/SpecialTopics/WomensHealth Research/UCM133184.pdf http://www.wiley.com/legacy/wileychi/eosbs/pdfs/bsa099.pdf Clinicaltrials.gov Schedule Y Dec. 2005 www.fda.gov/cder/handbook/phase2.htm Fundamentals of clinical trials- Lawrence M. Friedman, Curt Furberg, David L. DeMets - 1998