Amity Institute of Pharmacy

Clinical Trials I and II

M.Pharm, Ist Sem

Presented By:
Priyanshu Ranjan (A10651924012)
Supervised By:
Dr. Navneet Sharma

1
 Contents Amity Institute of Pharmacy

 Introduction
 Why do we need Clinical Trails
 Pre-Clinical Studies
 Investigational New Drug Application (INDA)
 Phase I of Clinical Trails
 Phase II of Clinical Trails
 References
 Introduction Amity Institute of Pharmacy

 Clinical trials are voluntary research studies conducted in people

and designed to acesss safety or effectiveness of drugs,
vaccines, other therapies, or new ways of using existing
treatments.

 Doctors use clinical trials to learn whether a new drug, treatment,

or combination works and is safe to use for people. Clinical trials
are important in developing new treatments for serious diseases
like cancer. All new treatments must go through clinical trials
before being approved by the Food and Drug Administration
(FDA). Clinical trials can take years to complete. It can take
months, if not years, to see if a cancer treatment does what it is
meant to do.
 Why do we need Clinical Trial Amity Institute of Pharmacy

 Clinical trials show us what works (and what doesn’t) in medicine and health care.
They are the best way to learn what works in treating diseases like cancer.
Clinical trials are designed to answer some important questions:

 Does the new treatment work in people? If it does, doctors will also look at how
well it works. Is it better than treatment now being used? If it’s not better, is it as
good and cause fewer side effects? Or does it work in some people who aren’t
helped by current treatments?
 Is the new treatment safe? No treatment or procedure – even one already in
common use – is without risk. But do the benefits of the new treatment outweigh
the risks?
 Is this treatment better than the standard treatment given for this disease? Clinical
trials help show if a new drug or treatment, or a new treatment combination,
works better than what is now used.
 Pre-Clinical Studies Amity Institute of Pharmacy

 Clinical trials are done only after pre-clinical findings suggest that the new drug or
treatment is likely to be safe and will work in people.

 Pre-clinical studies, also called laboratory studies, include:

 Cell studies: These are often the first tests done on a new treatment. To see if it
might work, researchers look for effects of the new treatment on diseased cells
that are grown in a lab dish or a test tube. These studies may be done on human
diseased cells.

 Animal studies: Treatments that look promising in cell studies are tested next on
disease in live animals. This gives researchers an idea of how safe the new
treatment is in a living creature.

 Pre-clinical studies work majorily in 4 areas Pharmacodynamic studies,

Pharmacokinectic studies (ADME), Acute-Chronic Toxicity studies and
Therapeutic Index (Safety and efficacy Evaluation).If the pre-clinical studies are
completed and the treatment still seems promising, the US Food and Drug
Administration (FDA) must give permission before the treatment can be tested
people.
 Amity Institute of Pharmacy

The Investigational New Drug (IND) Application

 Before a clinical trial can be started, the research must be approved. An
investigational new drug or IND application or request must be filed with
the FDA when researchers want to study a drug in humans. The IND
application must contain certain information, such as:
 Results from studies so that the FDA can decide whether the treatment
is safe for testing in people.
 The Components of IND Application includes: Pre-clinical data (from
animals),composition and drug source,chemical and manufacturing
information, proposed clinical plans and study protocols,ethical comittee
clearence.
 The research sponsor must commit to getting informed consent from
everyone on the clinical trial. They must also commit to having the study
reviewed by an institutional review board (IRB) and following all the rules
required for studying investigational new drugs
 Phases of Clinical Trial Amity Institute of Pharmacy

 Clinical trials are usually conducted in phases that build on one another.
Each phase is designed to answer certain questions. Knowing the phase
of the clinical trial is important because it can give you some idea about
how much is known about the treatment being studied. There are
benefits and risks to taking part in each phase of a clinical trial.

 Phase 0 studies use only a few small doses of a new drug in a few
people. They might test whether the drug reaches the site of action, how
the drug acts in the human body, and how diseased cells in the human
body respond to the drug. These studies mainy invlove Laboratory
Studies.

 Unlike other phases of clinical trials, there’s almost no chance the people
in phase 0 trials will benefit. The benefit will be for other people in the
future. And because drug doses are low, there’s also less risk to those in
the trial.
 Phase I Clinical Trial Amity Institute of Pharmacy

 Phase I studies of a new drug are usually the first that involve people.
Phase I studies are designed to access safety,tolerability,
Pharmacokinetics and Pharmacodynamics. These studies also help to
decide on the best way to give the new treatment.
Key points of phase I clinical trials
 The first few people in the study get a very low dose of the treatment and
are watched very closely. If there are only minor side effects, the next
few participants get a higher dose.
 Difference types of Sub-Studies under the Phase-I of Clinical trials
 Single Ascending Dose: A small group of subjects receive a single dose
of the study drug.
 Multiple Ascending Dose: A group of healthy volunteers or patients
receive multiple low doses of the drug.These studies are done to know
Drug-Dose Pharmacokinetics.
 Food Effect studies evaluate the effects of food on the bioavailability
(defined by the extent and rate of absorption) of orally administered New
Investigational Medicinal Products
 Drug-Drug Interactions Studies
 Phase I Clinical Trail Protocol Amity Institute of Pharmacy

Phase 1 trials primarily focus on assessing the safety, tolerability, pharmacokinetics

(PK), and pharmacodynamics (PD) of a drug.

Key Components of a Phase 1 Protocol

• Objectives: To evaluate the safety profile and determine the safe dosage
range.
To assess the pharmacokinetics (how the drug is absorbed, distributed,
metabolized, and excreted).
To evaluate the pharmacodynamics (the effects of the drug on the body).

• Study Design: Typically involves a small number of healthy volunteers (20-80

participants).
May include single ascending dose (SAD), multiple ascending dose (MAD), or
food-effect studies.
Open-label or single-blind designs are common.

• Inclusion/Exclusion Criteria: Detailed criteria to ensure the selection of

appropriate subjects (e.g., age, sex, health status).
Exclude subjects with certain medical conditions or those on medications that
could interfere with the study.
 Amity Institute of Pharmacy

• Safety Monitoring: Continuous monitoring for adverse events (AEs) and

serious adverse events (SAEs).
Predefined stopping rules for any significant safety concerns.

• Pharmacokinetic/Pharmacodynamic Assessments: Blood sampling

schedule for PK analysis.
Assessments for PD biomarkers relevant to the drug’s mechanism of action.

• Dose Escalation Strategy: A predefined plan for dose escalation based on

safety and tolerability data.
Use of a data monitoring committee (DMC) to review safety data before
proceeding to higher doses.

• Regulatory Compliance: Compliance with Good Clinical Practice (GCP)

guidelines.
Submission of an Investigational New Drug (IND) application to the FDA before
starting the trial.
Amity Institute of Pharmacy
 Amity Institute of Pharmacy

 Safety and dosage is the main concern.Approximately 70% of drugs

move to the next phase.While some people may benefit from being on
one, disease response is not the main purpose of a phase I trial,
 Placebos (inactive treatments) are not used in phase I trials.

 Phase I trials usually include a small number of people (20-100) and

Duration is from severals months (1-6 months usually).

 Phase I trials carry the most potential risk. But phase I studies do help
some patients. For those with life-threatening illnesses, weighing the
potential risks and benefits carefully is key. Sometimes people choose to
join phase I trials when all other treatment options have already been
tried.
 Phase II Clinical Trials Amity Institute of Pharmacy

Key points of phase II clinical trials

 A group of 20 to 300 patients with the same type of disease get the new
treatment in a phase II study.It determines the effectiveness of an
experimental drug on a particular disease or condition.

 This phase may last from several months to two years.

 Phase II Clinical Trails is divided into two sub-phases:
a. Phase IIa usually aims to decide the drug dosage and includes less than 100
patients, taking weeks or months.
b. Phase IIb studies the dose-response relationship, drug-drug interactions, and
comparison with a placebo.

A Proof of Concept study is an early-stage, exploratory clinical trial that collects

initial evidence regarding the efficacy of new chemical entities (NCEs) by
measuring their pharmacological activity. A clinical Proof of concept study
usually follows the acquisition of preclinical and early clinical safety data.
 Clinical Trail Phase II Protocol Amity Institute of Pharmacy

Phase II Clinical Trials are conducted to provide preliminary data on the drug’s
efficacy, as well as to further assess its safety in a larger population.

Key Components of a Phase 2 Protocol

• Objectives: To evaluate the efficacy of the drug for a specific indication.

To further assess safety and side effects in a larger patient population.
To identify optimal dosing regimens.

• Study Design: Typically involves a larger group of patients (100-300

participants) with the condition or disease the drug is intended to treat.
Randomized, controlled, and often double-blind designs are common.
Parallel-group or crossover designs may be used.

• Efficacy Endpoints: Definition of primary and secondary endpoints to assess

the drug’s efficacy.
Use of objective, validated, and clinically relevant outcome measures.
 Amity Institute of Pharmacy

• Safety Monitoring: Ongoing monitoring for adverse events, with more

emphasis on long-term safety data.
Implementation of stopping rules if safety concerns arise.

• Dose-Response Relationship: Evaluation of different dose levels to

determine the dose that provides the optimal balance between efficacy and
safety.

• Statistical Considerations: Sample size calculation to ensure the study is

adequately powered to detect a treatment effect.
Detailed statistical analysis plan (SAP) to specify the methods for data analyst.

• Regulatory Compliance: Continued adherence to GCP guidelines.

Submission of trial data to the FDA, with updates to the IND application as
necessary.
Amity Institute of Pharmacy
 Reference Amity Institute of Pharmacy

• https://www.fda.gov/patients/drug-development-process/step-3-clinical-
research#Clinical_Research_Phase_Studies

• https://www.fda.gov/patients/clinical-trials-what-patients-need-know/
what-are-different-types-clinical-research

• https://www.cancer.org/cancer/managing-cancer/making-treatment-
decisions/clinical-trials/what-you-need-to-know/phases-of-clinical-
trials.html

• https://cdsco.gov.in/opencms/export/sites/CDSCO_WEB/Pdf-
documents/GCT_PDFs/FAQ_CT.pdf
 Amity Institute of Pharmacy

THANK YOU