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Phase II Trials 

-D.Saikrishna

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Introduction

• Phase II includes the early controlledclinical studies conducted to obtainsome preliminary data on the

effectiveness of the drug for a particularindication in patients with the diseaseor condition

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• This phase of testing also helpsdetermine the common short-term sideeffects and risks associated with the

drug.• Phase II studies are typically well-

controlled, closely monitored, and

conducted in a relatively small numberof patients, usually involving severalhundreds of people.

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Objective

• Evaluate the effectiveness of a drug fora particular indication or indications inpatients with the condition under study

• Determine common short term sideeffects

• Risks associated with the drug

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Objectives

• Studies in Phase II should beconducted in a group of patients whoare selected by relatively narrow criteria

leading to a relatively homogeneouspopulation

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Objectives

• Theses studies should be closelymonitored

• An important goal for this phase is to

determine the dose (s) and regimen forphase III trials.

• Doses used in Phase II are usually (but

not always) less than the highest doseused in Phase I.

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Objectives

• Additional objectives can include evaluationof potential study endpoints, therapeuticregimens (including concomitantmedications) and target populations (e.g mildv/s severe disease) for further studies inPhase II and III.

• Theses objectives may be served by

exploratory analysis, examining subsets ofdata and by including multiple endpoints intrials.

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Regulation

• If the application s for conduct ofclinical trials as a part of multinationalclinical development of the drug, the

number of sites and the patients as wellas the justification for undertaking suchtrials in India shall be provided to the

Licensing Authority.

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Design

• Single-arm Phase II trial

• Each patient’s outcome is recorded and

noted if the desirable response to

therapy has been achived.

• If the observed response rate issufficiently high, this is used as the

rationale to conduct a confirmatoryPhase III trial.

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Types

• Sometimes divided into

-Phase IIA

-Phase IIB

• Phase IIA is specifically designed to assessdosing requirements (how much drug shouldbe given)

• Phase IIB is specifically designes to studyefficacy [how well the drug works at theprescribed dose(s)]

• Some trials combine Phase I and Phase II,

and test both efficacy and toxicity.

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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 forelderly or children

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Pharmacokinetic Studies

• Single dose pharmacokinetics

• Multiple dose pharmacokinetics (steadystate)

• Population pharmacokinetics• Special population pharmacokinetics

• Elderly

• Children• Organ impairment

• Fast/slow metabolizes

• Metabolism study

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Example-1

• Phase II Trial of Erlotinib in AdvancedPancreatic Cancer

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• Sponsor: University Health Network,Toronto

• Collaborator: OSI Pharmaceuticals

• Study Type: Interventional Study

• Design: Allocation: Non-Randomized

• Primary Purpose: Treatment

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Example-1

• Primary objective: To determine theefficacy of erlotinib, as measured by therate of disease control, in patients with

unresectable, locally advanced ormetastatic pancreatic adenocarcinoma.

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Example-1

• The presence of the erlotinib-induced rash isassociated with improved survival in Phase II and IIItrials of diverse tumor types, and is associated withhigher steady state concentrations of erlotinib

• This Phase II trial aims to dertimine the safety andefficacy of erlotinib in patients with advancedpancreatic cancer who have previously been treatedwith 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 developa rash is also evaluated

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• 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/WomensHealthResearch/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