CLINICAL TRIALS-

PHASES
 Introduction
 Any investigation in human subjects intended to discover or verify
the clinical, pharmacological and/or other pharmacodynamic
effects of an investigational product(s), and/or to identify any
adverse reactions to an investigational product(s), and/or to
study absorption, distribution, metabolism, and excretion of an
investigational product(s) with the object of ascertaining its safety
and/or efficacy. The terms clinical trial and clinical study are
synonymous.

 Multiphase study conducted by researchers on human subjects to

test a medical treatment or prevention strategy

 The medical treatment under examination could be a drug , a

surgical procedure, a medical device or a therapy
Phases:

Phases of Clinical Trials:

Phase 0: Exploratory IND Study
Phase I: Human Experimentation Trial
Phase II: Therapeutic Exploratory Trial
Phase III: Therapeutic confirmatory Trial
Phase IV: Post Marketing Surveillance
Phase V :If required
Phase 0:(Microdosing Study)-
Exploratory IND Study

 The purpose of this phase is to help speed up and streamline

the drug approval process.
 By definition, micro-dosing means use of ‘less than
1/100th of the dose calculated to yield a pharmacological
effect of the test substance to a maximum dose of < 100
micrograms (European Medicines Agency paper).
 The biggest difference between phase 0 and the later phases
of clinical trials is that there’s almost no chance the
volunteer will benefit.
 Objective:
• To find out whether the drugs do what they’re expected to
do.
• If there are problems with the way the drug is absorbed or
acts in the body, this should become clear very quickly in a
Advantages:

1.May shorten time periods to first-in-human studies*

2.Possibility to explore pharmacokinetic and
pharmacodynamic
3. Helps in accelerating the selection of promising
compounds, thus increasing the efficiency of the drug
development process.
4.Considering the reduced risk of human toxicity the
preclinical safety packages, animal use, amount of test
drug, development time and costs will be reduced.
5.This process may help avoid the delay and expense of
finding out years later in phase II or even phase III clinical
trials that the drug doesn’t act as expected to based on
lab studies.
 Disadvantages:

 In Phase 0 trials no therapeutic gain can be expected thus patient

participation may significantly affect the success rate of these trials.
 Question is whether there is a good correlation between the
pharmacokinetics of a microdose and of a therapeutically relevant dose.
  appropriate ONLY for compounds (e.g. small organic molecules, peptide
and protein therapeutics) with linear pharmacokinetics, small molecules with
short half-lives or compounds that are metabolized and that have a rapid
dissociation of binding to their target.
 Reliable assays and labs??
 Indeed, for microdose studies, very sensitive analytical methods are needed,
and currently these techniques are not routinely available.
 Phase I: (Human Experimentation
Trial)

 Study Participants: 20 to 100 healthy volunteers or people

with specific disease condition (Cancer/HIV etc.)
 Length of Study: 6 months- 1 year
 Purpose: Safety and dosage
 -PK study based on animal data to determine:
 highest dose of the new treatment that can be given safely
without serious side effects
 How much of a drug the body can tolerate. (MTD)
 What are its acute side effects.
 How it works in the body.
 The side effects associated with increased dosage.
 Early information about on efficacy.
 How best to administer the drug to limit risks and maximize
possible benefits.
Phase I:
 Calculation of LD-50 is generally consider while deciding dose of
drug in phase I study.
 Sub phases in Phase 1
Single Dose Phase 1 Study:
The first few people in the study often get a low and single dose of
the treatment and are watched very closely. If there are only minor
side effects

Multiple Dose Phase 1 Study:

Next few participants may get a higher and multiple dose. This
process continues until doctors find a dose that’s most likely to work
while having an acceptable level of side effects.
Phase I:
 Phase 1 Studies: Impact on
Labeling
 9.2 Abuse
 1 Indications And Usage  9.3 Dependence
 2 Dosage And Administration  10 Overdosage
 3 Dosage Forms And Strengths  11 Description
 4 Contraindications  12 Clinical Pharmacology
 5 Warnings And Precautions  12.1 Mechanism Of Action
 6 Adverse Reactions  12.2 Pharmacodynamics
 7 Drug Interactions  12.3 Pharmacokinetics
 8 Use In Specific Populations  13 Nonclinical Toxicology
 8.1 Pregnancy  13.1 Carcinogenesis, Mutagenesis,
 8.2 Labor And Delivery Impairment Of Fertility
 8.3 Nursing Mothers  13.2 Animal Toxicology And/Or
 8.4 Pediatric Use Pharmacology
 8.5 Geriatric Use  14 Clinical Studies
 9 Drug Abuse And Dependence  15 References
 9.1 Controlled Substance  16 How Supplied/Storage And Handling
 17 Patient Counseling Information
 Phase II: (Therapeutic
Exploratory Trial)

Study participants: 100-500

Length of study: 2-3 yrs.

Purpose:
 Conducted to evaluate the effectiveness of a drug in pts with

disease/condition under study & examine possible short term side effects
& risk associated with drug.

 Help to find answer to following:

 Is drug working by expected mechanism?
 Does it improve condition in question?
 What is optimal dose strength & schedules for drug?

Approximately 33% of drugs move to the next phase

Phase II:
Phase II trials are classified as:
1. Phase II a
2. Phase II b

Phase II a : Pilot Clinical Trial

 small scale, unblind & open label trial
 To confirm – procedures are safe & suitable

 To know dose range, initial efficacy evaluation, new indication/ to

determine the duration required etc.

Phase II b: Pivotal Clinical Trial

 Well planned, well controlled, open/ double blinded, placebo/

comparator controlled, may or may not be randomized, full scale trial.

 Such trials are conducted in units at 3-4 centers/sites with specialist

investigators with experience of particular indication, adequate

investigational facilities to monitor safety & efficacy.
 Phase III-(Therapeutic
confirmatory Trial)
 Study Participants: 1000-5000 Pts.(disease or condition)
 Length of Study: 2-10 yrs avg.5yrs
 Purpose:
 Efficacy and monitoring of adverse reactions
 To establish efficacy against existing therapy.
 To establish safety in relatively large no. of pts.
 To establish MTD usage in clinical practices.
 To identify contraindications, warnings for use of drug
 Phase III clinical trials compare the safety and effectiveness
of the new treatment against the current standard treatment.

Approximately 25-30% of drugs move to the next phase

 Phase III-
It is of 2 types
1.Phase III a
2.Phase III b

 Phase III a : These trials are conducted after efficacy of the

medicine is proved but prior to regulatory submission of a
New Drug Application (NDA).

 Phase III b : Clinical trials conducted after regulatory

submission of an NDA but prior to the medicine's approval
and launch.
 Phase IV: (Post Marketing
Surveillance Study)
 Study Participants: Several thousand volunteers who have the
disease/condition
 Purpose: Safety and efficacy on a larger and open scale
 Carried out once the drug or device has been approved by FDA.
 Approved drug are watched over a long period of time in phase IV
studies.
 Even after testing a new medicine on thousands of people, the full
effects of the treatment may not be known.
 These studies may involve thousands of people.
 This is typically the safest type of clinical trial because the
treatment has already been studied a lot and might have already
been used in many people.
 Phase IV studies look at safety over time.
 Adverse effects which are not seen in phase-III trials and those
which are rare can be identified.
 Phase V-(Extension to Phase IV)

 If a new dose, formulation or combination is

studied

 Additional human p’cology studies may be

indicated

 Necessitating a new development plan called

Phase-V trial.
References
1. The Drug Development Process > Step 3: Clinical
Research
https://www.fda.gov/forpatients/approvals/drugs/ucm4
05622.htm 1/6
2. American Cancer Society- What are Phases of
Clinical Trials?
https://www.cancer.org/treatment/treatments-and-side
-effects/clinical-trials/whatyou-need-toknow/phases-of-
clinical-trials.html