This presentation covers most frequently asked question in Interview on Clinical trial Phases.

1. CLINICAL TRIAL
PHASES
By Mr. Rohan Navgire
A student of Elite Institute of Pharma Skills
www. elite-pharmaskills.com

2. OVERVIEW
• Introduction- Clinical Research
• Drug development phases
• Pre-phase activity
• Phases of clinical trial
• Summary of Clinical trail phases

3. INTRODUCTION
• Clinical Research- clinical research refers to systemic
investigation in a human being for evaluating the safety and
efficacy of new drug.
• The worldwide pharmaceutical industry is taking major steps in a
drug development and newer and better drugs being introduced
for protecting human life through clinical research.
• Three important stages for bringing new drug to market-
1. Drug discovery
2. Pre-clinical testing
3. Clinical trial

4. • It takes about 12- 15 years from discovery to the approved
medication and requires an investment of about US $ 1billion.
• On an average, from more than a million screened molecules
only one is investigated in late stage clinical trail and is finally
made available for patients.
• It requires apporx 6-7 years for carrying out various phases os
clinical trial.

5. REQUIREMENT FOR GLOBAL
CLINICAL RESEARCH
 Infrastructure
 Regulatory Environment
 Patient Pool-Genetic Diversity
 I.P Protection
 Investigator Availability
 Bioethics Regulation
 Cost advantage

6. DRUG DISCOVERY

7. DRUG REVIEW STEPS
1. Preclinical (animal) testing.
2. An investigational new drug application (IND).
3. Phase 1 studies
4. Phase 2 studies
5. Phase 3 studies
6. Submission of New Drug Application (NDA)
7. FDA reviewers will approve the application or find it either
"approvable" or "not approvable."
8. Phase 4 studies

8. PRECLINICAL STUDIES
• Preclinical studies perform on animal
• Objective –
1. Pharmacodynamics studies in vivo in animal, In vitro preparation
2. Pharmacokinetic studies(ADME)
3. Toxicity Profile
4. Therapeutic index

9. PHASES OF CLINICAL TRIAL
• Phase 0 (Micro dosing study)
• Phase 1 (Human Pharmacology)
• Phase 2 (Therapeutic Exploratory)
• Phase 3 (Therapeutic Confirmatory)
• Phase 4 (Post Marketing Surveillance)

10. PHASE 0 (MICRO DOSING STUDIES)
• Study of new drug in micro doses to derive PK information
in human before undertaking phase I studies is called
PHASE O
• Micro dose- Less than 1/100 of the dose of a test substance
calculated to produce pharmacological effect with a max
dose ≥100 micrograms.
• Objective- To obtain preliminary Pharmacokinetic data.
• Preclinical data- : Sub acute toxicity study in one species by
two routes of administration.

11. Advantages-
Less chance of adverse effects
Short duration
Less no. of volunteers
Reduced costof development
Reduced drug development time
Limitations-
Study mainly based on PKparameters - not efficacy and safety based
Of Limited use for agents having Non linear PKs
Agents having different kinetic characteristics between micro dose and full dose arenot
evaluated by phase 0 trials

12. PHASE 1 (HUMAN PHARMACOLOGY)
• Why phase 1
-The primary concern- Assessment of the drug’s safety and safe
effective dose for further studies
• Objective
Assessment of the drug’s safety and safe effective dose for
further phase studies
To determine what happens to the drugs in the human body
To determine the dose level of the drug
To evaluate how a new drug should be administered
Side effects of the drug

13. • Dose in Phase 1
- SAD: Single Ascending Dose
- MAD: Multiple Ascending Dose
- Food effect- investigate differences in absorption caused by food
• Subject
- Healthy male volunteers(Small number-10to30)
- Patient volunteers- cytotoxic drugs, AIDS therapy
• Limitations
-Trial restricted to homogenous subjects.
-Performance extrapolated to heterogeneous market place.

14. PHASE 2 (THERAPEUTIC
EXPLORATORY)
• Consists of 20-300 subjects
• Toconfirm effectiveness, monitor side effects, &further
evaluate safety.
• First in patients (who have the disease that the drug is
expected to teat).
• Duration- 2 to several years
• Optimum dose binding:
Dose efficacy relationship, Therapeutic dose regimen, Duration of
therapy
Frequency of administration, Therapeutic window

15. • Phase 2 study type
Phase II a- to assess dosing requirement
Phase II b- to study efficacy

16. PHASE 3(THERAPEUTIC
CONFIRMATORY)
• Phase 3 primary objective is to demonstrate, or confirm therapeutic benefit.
• Phase 3 studies generally conducted in large number of patients (about
1000 to 5000)
• Duration- 2 to 10 years (with average length of 5 years)
• Objective of phase 3-
1. To establish efficacy of the drug against existing therapy
2. To establish the safety in relatively large number of patients
3. To establish method usage in clinical practices
4. To identify contraindications, warnings for use of drug

17. • Phase III subtype
Phase IIIa- to get sufficient and significant data
Phase III b- allow patient to continue treatment also known as label expansion

18. PHASE 4 (POST MARKETING
SURVEILLANCE)
• Phase IV studies continues after approval of drug. As much larger number
of people/patients with difference in diet, habits, age, gender etc. beings to
use the drug.
• Objective of phase IV-
1. Determine the behavior of the drug when used in real life situation
without the dietary control of commonly used items like nicotine and
alcohol.
2. Determine if at all any missed rare adverse reaction or adverse reaction
coming late
3. To evaluate the action of the drug in a situation missed dosage or over
dosage

19. • Phase Iv population
1. May conducted in clinics, hospitals and private practice.
2. All patients with target disorder, but with greater heterogeneity
3. Include all types of patients for whom the drug may be indicated
• REPORTING OF ADR:
1.The ADR can be reported to a formal reporting system such as:
2.WHO International System
3.USFDA- Medwatch
4.UK-Yellow cardsystem
5.INDIA- National Pharmacovigilance Programme (CDSCO)

20. SUMMARY OF PHASES IN CLINICAL
TRIAL