1. CLINICAL TRAILS
SUBMITTED BY: SUBMITTED TO:
VENKATESWARLU UNNAM. Dr. G. RAMESHpharm-d
115AB1T0026. DEPARTMENT OF PHARMACY
IV PHARM-D PRACTICE
2. CONTENTS:
• Introduction to clinical trail
• Types of clinical trails
• Classification of various phases of clinical trails
phase 0 trails
phase 1 trails
phase 2 trails
phase 3 trails
phase 4 trails
• Conclusion
3. INTRODUCTION TO CLINICAL TRAIL:
• “A systematic study of pharmaceutical products on human
subjects (whether patients or non patients volunteers) in order
or verify the clinical, pharmacological (including
pharmacodynamics and pharmacokinetics) and or adverse
effects, with the object of determining their safety and efficacy”
• Carefully conducted clinical trails are the fastest and the safest
way to find treatments that work in people and ways to improve
health.
• Clinical trail is the main stay for bringing out new drugs to the
market.
4. TYPES OF CLINICAL TRAILS
• Treatment trail
• Prevention trail
• Early detection/ screening
• Diagnostic trail
• Quality of life/ supportive trail
5. CLASSIFICATION OF VARIOUS PHASES
OF CLINICAL TRAILS:
• There are 5 different phases of clinical trails, which include:
• Phase 0 trails ( micro dosing trials)
• Phase I trails ( human pharmacology/ first time in man studies)
• Phase II trails (pilot trails/ therapeutic exploratory trails)
• Phase III trails (expanded clinical trails/ therapeutic confirmatory
trails)
• Phase IV trails (post marketing trails)
6.
7. PHASE 0 TRAILS/ MICRO DOSING TRAILS:
• Micro dosing/ human phase 0 clinical trails, is a technique whereby
sub pharmacological doses or prospective drug candidates are
administered to human volunteers.
• A micro dose studyprovides early pharmacokinetic data in humans
and only requires minimal pre-clinical toxicology safety testing.
• A micro dose is defined as 100th of the pharmacological dose (or
predicted pharmacological dose) or a maximum of 100µg
8. 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.
9. PHASE I TRAILS:
• Phase I trials are the first stage of testing in human subjects.
• 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
Inclusion criteria:
• Healthy volunteers: uniformity of subjects: age, sex, nutritional
status
• Exception: patients only for toxic drugs eg anti HIV, Anticancer
Exclusion criteria:
• Women of child bearing age, children
10. Purpose:
• To determine the safety of the investigational drug
• Other objectives include: To determine..
• Maximum tolerated dose (MTD)
• Phramacokinetics
• Phramacodynamics
• Early measurement of drug activity
Study design:
• Un- blinded, un-controlled study
No. of subjects:20-60
Length of studies: several months
11. PHASE II TRAILS:
• Phase II studies are designed to explore the therapeutic efficacy of a
treatment or drug in people who have the condition that the drug is
intended to treat.
• They are some times called therapeutic explorat1ory trails and tend
to be larger scale than phase 1 trails.
• Many experimental drugs which fail tend to do so during the phase II
trails.
Purpose:
• To demonstrate efficacy with particular disease .
• An important goal for this phase is to determine the dose(s) and
regimen for phaseIII trails.
12. Study design: single blinded, placebo controlled
Subjects involved:
• Subjects in phase II trails are patients with the disease or clinical
situation being examined .
• They should be healthy in terms of their disease and free of other
serious medical illness .
Length of studies: few months or take upto several years.
No. of subjects: 60-200
• Phase II trails can be divided into phase IIA and phase IIB although
some times both are combined.
13. Phase IIA: is desgined to assess dosing requirements that is how much
of the drug should patients receive and up to what dose is considered
safe.
• the safety assaessment carried out in phase I can be repeated on a
larger subject group.
• As more subjects are involved, some may experience side effects
which none of the subjects in the phaseI is experienced.
• The researcers aim to find out more about safety, side effects and
how to manage them.
Phase IIB: studies focus on the efficacy of the drug that is how well it
works at the prescribed doses.
• Researchers may also be interested in finding of which types of a
specific disease or condition would be most suitable for treatment.
14. PHASE III TRAILS:
• Phase III trails are the last stage before clinical approval for a new drug or device.
• Studies in phase III may also further explore the dose-response relationships, use of
the drug in wider populations, in different stages of disease, or the safety and
efficacy of the drug in combination with other drugs.
Purpose:
• Phase IIIa trails are designed to gain safety and efficacy information in a large
number of patients.
Study design: randomised controlled, double bind cross over designs.
Subjects involved: phase 3 subjects are patients exhibiting the disease under study are
selected from a larger population of patients.
Length of studies: phase IIIa studies tend to be of longer duration, lasting 1-4 years.
15. Phase IIIb (large-scale trails:
Purpose:
• The purpose of phase IIIb trails is to gain experience with the experimental agent in a
large number of subjects that reflect the general population at risk.
• Therefore, the trails are less tightly controlled, all the subjects may be receiving
experimental drug, and entry criteria are relaxed and larger numbers of patients are
enrolled.
subjects involved:
• Phase IIIb trail subjects come from a larger, heterogenous patient population.
• The subject population may focus on specific concurrent illness to further delineate the
drug’s safety.
Length of studies:
• Phase IIIb studies last 1-4 years and used to gather additional data investigational agent.
16. NDAAPPLICATION:
• New drug application (NDA) is done following successful
completion of all 3 phases of human clinical trails, the company
analyses all of the data and files an NDA with the FDA if the data
successfully demonstrate safety and effectiveness.
• The NDA must contain all of the scientific information that the
company has gathered on the compound.
• NDAs can exceed 100,000 pages or more.
• By legislation, the FDA is allowed 6 months to review an NDA
filing.
17. PHASE IV TRAILS:
• After the 3 phases of clinical testing and after the treatment has been
approved for marketing, there may be a 4th phase to study the long term
effect of drugs or treatments or to study the impact of another factor in
combination with the treatment (eg. Whether a particular drug reduces
agitation).
• Usually, such trails are sponsored by pharmaceutical companies and
described as pharmacovigilance.
• Purpose: Phase IV trails include additional drug-drug interactions, dose
response or safety studies and trails designed to support use under the
approved indications, e.g: mortality/ morbidity studies, epidemiological
studies
18. Study design: un controlled, observational.
Subjects involved: subjects in phase IV trails are drawn from the
general population with specific disease.
• Further conditions are defined by the purpose of the protocol.
Length of studies: the length of phase IV trails is determined by the
purpose of the study and may be indefinite, such as in post
marketing surveillance.
19.
20. CONCLUSION:
• Clinical trial is a human experiment designed to study the efficacy and
safety of a new drug/intervention
• Involves Phase 1-4 with specific objectives and end results
• Application to Regulatory authority:
• IND – Permission to conduct CT
• NDA – Permission to Market New drug
• Well designed and effectively executed clinical trials form the base of
therapeutic decisions
• CT must follow guidelines & protocol to ensure well-being of participants
21. REFERENCE:
• Greenwood, D.T. and Todd, A.H.(1977) In Clinical Trials.Johnson,
F.N. and Johnson, S., eds.,Blackwell Scientific Publications,
Oxfords.
• Guidelines for Clinical Trials on Pharmaceutical Products in
India(2201) Published by the Ministry of health and Family Welfare,
Government of India, New Delhi.
• en.wikipedia.org
• www.pharmadost.com
