Clinical drug development

CDD-2016, Phuket, Thailand. 1

Clinical Drug Development

Prof. Dr. Basavaraj K. Nanjwade M. Pharm., PhD

Department of Pharmacy PracticeThe Oxford College of Pharmacy

Bengaluru-560068, Karnataka, India.

02/06/2016



• 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


New Drug Development

02/06/2016


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


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



• 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


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


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


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


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. 1102/06/2016


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


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


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


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


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


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


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


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


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


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


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


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


Phase IV Clinical Trial

• Patients: Several thousand volunteers who have the disease/condition

• Purpose: Safety and efficacy

02/06/2016


Study Types Included• Post Marketing Surveillance studies

• Studies intended to support publication claims

02/06/2016


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/ucm405622.htm

• http://www.camargopharma.com/clinical-studies phases-i-iv.aspx

• http://www.cailsilorin.com/safety-and-efficacy/

02/06/2016


THANK YOU02/06/2016

Date post:	21-Apr-2017
Category:	Health & Medicine
Upload:	prof-dr-basavaraj-nanjwade
View:	17 times
Download:	0 times

Clinical drug development

Health & Medicine