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

2. Clinical Drug Development
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.
02/06/2016
CDD-2016, Phuket, Thailand.

3. New Drug Development
02/06/2016
CDD-2016, Phuket, Thailand.

4. 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
02/06/2016
CDD-2016, Phuket, Thailand.

5. 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.

6. Clinical Drug Development
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
02/06/2016
CDD-2016, Phuket, Thailand.

7. Clinical Drug Development
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)
02/06/2016
CDD-2016, Phuket, Thailand.

8. Clinical Drug Development
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
02/06/2016
CDD-2016, Phuket, Thailand.

9. 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.
02/06/2016
CDD-2016, Phuket, Thailand.

10. 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).
02/06/2016
CDD-2016, Phuket, Thailand.

11. 02/06/2016
CDD-2016, Phuket, Thailand.

12. 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.
02/06/2016
CDD-2016, Phuket, Thailand.

13. 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%
02/06/2016
CDD-2016, Phuket, Thailand.

14. 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
02/06/2016
CDD-2016, Phuket, Thailand.

15. 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.
02/06/2016
CDD-2016, Phuket, Thailand.

16. 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.
02/06/2016
CDD-2016, Phuket, Thailand.

17. 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%
02/06/2016
CDD-2016, Phuket, Thailand.

18. 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
02/06/2016
CDD-2016, Phuket, Thailand.

19. 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.)
02/06/2016
CDD-2016, Phuket, Thailand.

20. 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%
02/06/2016
CDD-2016, Phuket, Thailand.

21. 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.
02/06/2016
CDD-2016, Phuket, Thailand.

22. 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
02/06/2016
CDD-2016, Phuket, Thailand.

23. 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.
02/06/2016
CDD-2016, Phuket, Thailand.

24. Phase IV Clinical Trial
Patients: Several thousand volunteers who have the disease/condition
Purpose: Safety and efficacy
02/06/2016
CDD-2016, Phuket, Thailand.

25. Study Types Included Post Marketing Surveillance studies
Studies intended to support publication claims
02/06/2016
CDD-2016, Phuket, Thailand.

26. REFERENCES
Namrata Bahadur, Overview of Drug Development, Head of Clinical Development & Medical Affairs Emerging Growth Markets, 17th - 21st March, Bangkok.
phases-i-iv.aspx
02/06/2016
CDD-2016, Phuket, Thailand.

27. THANK YOU
02/06/2016
CDD-2016, Phuket, Thailand.