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1.Introduction

2.Phases of Clinical Trial:

a . phase 0

b . Phase 1

c. Phase 2

d . Phase 3

e . Phase 4

3.Conclusion

4.References

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Introduction

Clinical trial:

Any investigation in human subjects

intended to discover or verify the clinical,

pharmacological, and other pharmacodynamic

effect of an investigational product and to identify

any adverse reactions to an investigational product,

and to study absorption, distribution, metabolism,

excretion of an investigational product with the

object of ascertaining its safety and efficacy.

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Phases of clinical trial

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Phase 0

• Phase 0 is a recent designation for exploratory, first-in-human

trials conducted in accordance with the United States Food and

Drug Administration's (FDA) 2006 Guidance on

Exploratory Investigational New Drug (IND) Studies. Phase 0

trials are also known as human micro dosing studies.

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Distinctive features of Phase 0

Primary goal:- Pharmacodynamic and Pharmacokinetic

particularly oral bioavailability and half-life of the drug.

Dose: it is 1/100th of therapeutic dose.

Subjects: 10-15 healthy volunteers.

A Phase 0 study gives no data on safety or efficacy, being by

definition a dose too low to cause any therapeutic effect.

Phase 0 clinical trial are not mandatory. They are case to

case based.

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Phase 1

Phase I trials are the first stage of testing in human subjects.

Normally, a small group of 20–100 healthy volunteers will be

recruited.

Phase I trials also normally include dose-ranging, also called

dose escalation studies, so that the best and safest dose can be

found and to discover the point at which a compound is too

poisonous to administer

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Distinctive features of Phase 1

Primary goal: To assess the safety (pharmacovigilance),

tolerability, pharmacokinetics, and pharmacodynamis of a

drug.

These trials are often conducted in an inpatient clinic, where

the subject can be observed by full-time staff.

Phase I trials most often include healthy volunteers.

The tested range of doses will usually be a fraction of the

dose that caused harm in animal testing.

Volunteers are paid an inconvenience fee for their time spent

in the volunteer centre. Pay depends on length of participation.

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Single ascending

dose

Food effect

Multiple ascending

dose

Different kinds of phase1 trial

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Phase 2

Once a dose or range of doses is determined, the next

goal is to evaluate whether the drug has any

biological activity or effect. Phase II trials are

performed on larger groups (100-300) and are

designed to assess how well the drug works, as well

as to continue Phase I safety assessments.

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Types of Phase 2

Phase 2a How much drug should

be given

Phase 2bHow well the drug

response to the dose

Phase 2

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Distinctive features of phase 2a

Primary goal: To determine the therapeutic efficacy.

Pilot trials: Dose response determination, determine

dose regimen and determination of target population.

Subjects: Few hundreds . Patients fitting narrow

eligibility criteria.

Trial design: Comparison with baseline status. Open

level or single/ double-blind.

Dose escalation.

Parallel dose response.

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Distinctive features of Phase 2b

Pivotal studies.

Objectives: Focus on aspects of phase 2a trial.

Blinding.

Placebo or other concurrent control.

Crossover treatments.

Multicenter.

Subjects: similar to phase 2a.

Trial design: Single or double blinded.

Conducted at multiple sites.

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Phase 3

Phase III studies are randomized controlled multicenter

trials on large patient groups (300–3,000 or more

depending upon the disease/medical condition

studied) and are aimed at being the definitive

assessment of how effective the drug is, in

comparison with current 'gold standard' treatment.

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Types of Phase 3

Phase 3a:

Subjects: large.

Trial design: open level or single or double blinded.

Multicenter.

Testing different stages of the disease indication.

Dosage forms , formulation

Different routes.

Pharmacoeconomic evaluation.

Phase 3b: Phase III trials will

continue while the regulatory

submission is pending at the

appropriate regulatory agency.

This allows patients to continue to

receive possibly lifesaving drugs

until the drug can be obtained by

purchase. i.e. Antiretroviral,

Anticancer etc.

Peri-approval studies.

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Phase 4

Phase IV trial is also known as post marketing surveillance Trial. Phase IV

trials involve the safety surveillance (pharmacovigilance) and ongoing

technical support of a drug after it receives permission to be sold. The

safety surveillance is designed to detect any rare or long-term adverse

effects over a much larger patient population and longer time period than

was possible during the Phase I-III clinical trials. Harmful effects

discovered by Phase IV trials may result in a drug being no longer sold, or

restricted to certain uses: recent examples involve cerivastatin (brand

names Baycol and Lipobay), troglitazone (Rezulin) and rofecoxib (Vioxx).

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Conclusion

Clinical trial may occur in several different phases .

Drug are developed in several different phases to

meet the multiple objective in the safest, most

efficient manner. Phase is only a description and

not a set of rules.

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References

en.wikipedia.org

http://www.alzheimer-europe.org

http://www.centerwatch.com

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