Clinical drug development

Clinical Drug Development
Prof. Dr. Basavaraj K. Nanjwade M. Pharm., PhD
Department of Pharmacy Practice
The Oxford College of Pharmacy
Bengaluru-560068, Karnataka, India.
02/06/2016 1CDD-2016, Phuket, Thailand.

• Patients make an incredible contribution when
they choose to participate in a clinical drug
development/clinical drug research/clinical trials.
• Actively finding ways to help minimize burden on
the selected patients and make studies more
patient-friendly and patient compliance.

New Drug Development

Targets for Drug Development
• Oncology: Angiogenesis, cell signalling receptors
and molecules in tumour growth.
• Cardiovascular and metabolic diseases: Type 2
diabetes, obesity, atherosclerosis/thrombosis
• CNS: Alzheimer’s Disease, Parkinson’s disease,
affective disorders

Targets for Drug Development
• HIV / AIDS: Novel targets in viral life cycle
• Infectious diseases: Hepatitis B and C, influenza
• Asthma: Chronic Obstructive Pulmonary Disease
(COPD)
• Autoimmune and inflammatory diseases: Arthritis,
psoriasis, inflammatory bowel disease, multiple
sclerosis
02/06/2016 CDD-2016, Phuket, Thailand. 5

• Bioavailability
• Bioequivalence
• Cross-over designs
• Comparison
• Dose-ranging
• Special populations (renal, hepatics, elderly)
• Drug-drug interactions
• Drug interaction
• Drug metabolism
• Safety and efficacy
• Patient selections

• How it is absorbed, distributed, metabolized, and
excreted
• Its potential benefits and mechanisms of action
• The best dosage
• The best way to give the drug (such as by mouth or
injection)

• Side effects (often referred to as toxicity)
• How it affects different groups of people (such as by
gender, race, or ethnicity) differently
• How it interacts with other drugs and treatments
• Its effectiveness as compared with similar drugs

Future Directions
• Need to focus drug development on safety and
efficacy.
• Early detection of potential pitfalls using biomarkers,
surrogate markers, imaging techniques, phase 0 trials.
• Complexity of the mechanisms of disease such as
oncogenesis/tumorigenesis may require targeting
multiple targets in sequence.

Future Directions
• Complexity of the mechanisms of disease should
drive future research to better understand the
mechanisms and translate knowledge into clinical
drug research
• Need to continue focus on developing products to
address potential urgent public health needs (e.g.,
pandemic influenza).

Phase I Clinical Trial
(INITIAL SAFETY TESTING IN A SMALL GROUP OF HEALTHY VOLUNTEERS )
• In Phase I trials the candidate drug is tested in people for the first
time.
• These studies are usually conducted with a small number of healthy
volunteers, generally 100 or less.
• The main goal of a Phase I trial is to assess the safety of the
medicine when used in humans.
• Researchers look at the pharmacokinetics of a drug: How is it
absorbed?
• How is it metabolized and eliminated from the body?
• They also study the drug’s pharmacodynamics: Does it cause side
effects?
• These closely monitored trials are designed to help researchers
determine what the safe dosing range is and if the candidate
medicine should move on to the next stage of development.

Phase I
• Patients: 20 to 100 healthy volunteers or people with
the disease/condition.
• Length of Study: Several months
• Purpose: Safety and dosage
• Percentage of Drugs that Move to the next Phase
70%

Study Types Included
• Safety & Tolerability studies (Single/ multiple dose in
patients or healthy volunteers)
• Oncology studies in patients with tolerability / MTD
as primary endpoint (efficacy might be a secondary
endpoint)
• Drug-Drug interaction & Food Effect
• PK in renal or hepatic impaired patients

Phase II Clinical Trial
(ASSESS SAFETY AND EFFICACY IN A SMALL GROUP OF PATIENTS)
• In Phase II trials researchers evaluate the candidate
drug’s effectiveness in 100 to 500 patient volunteers
with the disease or condition under study.
• Researchers also analyze optimal dose strength and
schedules for using the drug and examine the possible
short-term side effects (adverse events) and risks
associated with the drug.
• If the drug continues to show promise, they prepare
for the much larger Phase III trials.

Phase II
• Phase IIA: Exploratory (non-pivotal) study that has
clinical efficacy, Pharmacodynamics or biological
activity as primary endpoint, conducted in patients or
healthy volunteers.
• Phase IIB: Definite dose range finding study in
patients with efficacy as primary endpoint.

Phase II
• Patients: Up to several hundred people with the
disease/condition.
• Length of Study: Several months to 2 years
• Purpose: Efficacy and side effects
• Percentage of Drugs that Move to the Next Phase
33%

Study Type Included
• Proof of concept, efficacy, or mechanism
• Mechanistic studies
• Dose range exploration
• Pilot studies
• Definite dose finding studies
• Extension studies of Phase IIB studies

Phase III Clinical Trial
(DEMONSTRATE SAFETY AND EFFICACY IN A LARGE GROUP OF PATIENTS)
• Phase III trials generate statistically significant data about
the safety, efficacy and the overall benefit-risk
relationship of the investigational medicine.
• Phase III trials may enroll 1,000 to 5,000 patients or more
across numerous clinical trials sites around the world.
• This phase of research is essential in determining whether
the drug is safe and effective.
• It also provides the basis for labeling instructions to help
ensure proper use of the drug (e.g., information on
potential interactions with other medicines, specific
dosing instructions, etc.)

Phase III
• Patients: 300 to 3,000 volunteers who have the
disease or condition
• Length of Study: 1 to 4 years
• Purpose: Efficacy and monitoring of adverse
reactions
• Percentage of Drugs that Move to the Next Phase
25-30%

Phase III
• Phase IIIA: A Pivotal study that is a trial designed &
executed to get statistically significant evidence of
efficacy and safety as required NDA/ sNDA approval. It
also provides the basis for labeling instructions to help
ensure proper use of the drug (e.g., information on
potential interactions with other medicines, specific
dosing instructions, etc.)
• Phase IIIB: A study started prior to approval and whose
primary intention is support of publications rather than
registration or label changes. The results are not intended
to be included in the submission dossier.

Study Time Included
• Pivotal studies (vs placebo/comparator)
• Long term safety studies for registration
• Local registration studies
• Post marketing study commitments
• Phase IIIA extension studies
• Studies intended to support publication, claims or
to prepare launch, which start before approval but
are not intended for Regulatory submissions

Phase IV
• Phase IV: A study started after approval with primary
intention to support publications rather than
registration or label changes.
• The results are not intended to be included in a
submission dossier.

Phase IV Clinical Trial
• Patients: Several thousand volunteers who have the
disease/condition
• Purpose: Safety and efficacy

Study Types Included
• Post Marketing Surveillance studies
• Studies intended to support publication claims

REFERENCES
• Namrata Bahadur, Overview of Drug Development,
Head of Clinical Development & Medical Affairs
Emerging Growth Markets, 17th - 21st March, Bangkok.
• http://www.phrma.org/sites/default/files/pdf/rd_brochure_
022307.pdf
• http://www.fda.gov/ForPatients/Approvals/Drugs/ucm405
622.htm
• http://www.camargopharma.com/clinical-studies phases-i-
iv.aspx
• http://www.cailsilorin.com/safety-and-efficacy/

THANK YOU

Clinical drug development

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Clinical drug development