Module II: The Trial Landscape

Contents
„ Why clinical trials?
„ Main features of clinical trial design
„ The history of clinical trials
„ The drug development process
„ Phases of clinical trials
„ Clinical trial players
„ Trial guidelines - GMP, GLP and GCP
„ Quality assurance – audits and inspections
„ Research ethics
„ Risk and benefits of trial participations

Phases of Clinical Trials

The stages
New Drug
Application (NDA)
Phase IV
Investigational
New Drug (IND) Phase III
Application
Phase II

Phase I

Pre-clinical Clinical

Phases of Clinical Trials

Pre-clinical stage
develop a pharmacological profile
of the drug;
determine the acute toxicity of the
drug in at least two species of
animals;
conduct short-term toxicity studies
ranging from 2 weeks to 3 months.

Pre-clinical Stage Clinical Stage

Lab Tests Human Trials
Animal Studies

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 Phases of Clinical Trials
IND gives the results of
pre-clinical
experiments
how and where the
Investigational compound will be
New Drug (IND) tested
Application

Pre-clinical Clinical

Phases of Clinical Trials

Phase I New Drug Application (NDA)

drug's toxicity, absorption,

distribution, metabolism,
excretion, the duration of
action, drug-to-drug
interaction and drug-to-
Phase IV
food interaction

Phase III
5-20 studies
1-30 days Phase II

100-400 subjects Phase I

Phases of Clinical Trials

Phase II
New Drug Application
(NDA)

Show efficacy
Is it effective?

Phase IV

Phase III
3-6 studies
1 week – 6 months Phase II

200-600 subjects Phase I

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 Phases of Clinical Trials
Phase III
New Drug Application
(NDA)
Prove efficacy
How does it compare with
standard treatment or
placebo?
Phase IV

Phase III
1-4 studies
1 week – years Phase II

1000-20000 subjects Phase I

Phases of Clinical Trials

NDA
New Drug
Application (NDA)
Phase IV

Phase III

Phase II

Phase I

Clinical

Phases of Clinical Trials

Phase IV
New Drug
Application (NDA)

Long-term follow up
evaluate long-term effects
on morbidity and mortality,
and also any side-effects Phase IV

Phase III

Phase II

Phase I

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 Phases of Clinical Trials
Phases combined

Phase IV

Phase IIIa
Phase III
Phase IIIb
Phase II/III
Phase IIa
Phase II
Phase IIb
Phase I/II
Phase Ia
Phase I
Phase Ib

Phases of Clinical Trials

Another terminology
Therapeutic
Use

Therapeutic Phase IV
Confirmatory
Phase III

Therapeutic Phase II
Exploratory
Phase I

Human Clinical
Pharmacology

Phases of Clinical Trials

Example: Cancer Drug
4 Phase III trials
4200 patients

Phase III

6 Phase II trials
Phase II 320 patients

Phase I 11 Phase I trials

240 healthy
volunteers / patients

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 Phases of Clinical Trials
Example: Diabetes Drug
3 Phase III trials:
0.5-2 years
3900 patients
Phase III

3 Phase II trials:
Phase II
1 – 6 months
430 patients

Phase I
20 Phase trials:
1 – 14 days
450 subjects

Phases of Clinical Trials

IB contents
CONTENTS OF INVESTIGATOR'S BROCHURE (Example)

Introduction
Physical, Chemical, and Pharmaceutical Properties
Formulation
Nonclinical Studies
Nonclinical Pharmacology
Pharmacokinetics and Product Metabolism in Animals
Toxicology
Effects in Humans
Pharmacokinetics and Product Metabolism in Humans
Safety and Efficacy
Marketing Experience
Summary of Data and Guidance for the Investigator
References on Publications and Reports

Conclusion
Phases of Clinical Trials

„There are four phases of clinical trials:

zPhase I - Human Pharmacology
zPhase II - Therapeutic Explorative
zPhase III - Therapeutic Confirmatory
zPhase IV - Therapeutic Use.

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