Clinical studies and trials on traditional medicine and natural products

20th World Congress on Clinical Nutrition, Bangakok, Thailand

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Clinical Studies and Trials on Traditional Medicine and

Natural Products

Prof. Dr. Basavaraj K. NanjwadeDepartment of Pharmaceutics

Rani Chennamma College of Pharmacy,Belagavi-590010, Karnataka, INDIA.

E-mail: [email protected]

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The Ultimate Goal

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Discovery, Design and Development

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Medicines research

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Clinical Pharmacokinetics• Clinical pharmacokinetics is the process of applying

pharmacokinetic principles to determine the dosage regimens of specific drug products for specific patients to maximize pharmacotherapeutic effects and minimize toxic effects.

• TDM stands for therapeutic drug mointoring

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Clinical Pharmacokinetics

• Application of these principles requires an understanding of the absorption, distribution, metabolism, and excretion characteristics of specific drug products in specific diseases and patient populations

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Pharmacokinetics

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Clinical Studies

• Treatment studies1. Randomized controlled trial

– Blind trial– Non-blind trial

2. Adaptive clinical trial3. Nonrandomized trial (quasi-experiment)

– Interrupted time series design (measures on a sample or a series of samples from the same population are obtained several times before and after a manipulated event or a naturally occurring event) - considered a type of quasi-experiment

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Clinical Studies

• Observational studies1. Cohort study

– Prospective cohort– Retrospective cohort– Time series study

2. Case-control study– Nested case-control study

3. Cross-sectional study– Community survey (a type of cross-sectional study)

4. Ecological study

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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

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Steps in Pharmaceutical Products

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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.

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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%

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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

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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.

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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.

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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%

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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

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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.)

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Phase III• Patients: 100 to 5000 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%

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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.

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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

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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.

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Phase IV Clinical Trial

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

• Purpose: Safety and efficacy

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Patient care

Knowledge of drug therapy

Knowledge of the disease

Knowledge of laboratory

and diagnostic skills

Communication skillsPatient

monitoring skills

Physical assessment

skills

Drug Information

Skills

Therapeutic planning

skills

Knowledge of nondrug

therapy


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Reference• 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/• http://www.yourgenome.org/facts/how-are-drugs-designed-and-developed

.• http://cenblog.org/the-haystack/2012/02/drug_design/• Anurag S Rathore & Helen Winkle Quality by design for

biopharmaceuticals. Nature Biotechnology 27, 26 - 34 (2009), doi:10.1038/nbt0109-26.

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

http://www.yourgenome.org/facts/how-are-drugs-designed-and-developed

http://cenblog.org/the-haystack/2012/02/drug_design/


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THANK YOU14/12/206

E-mail: [email protected]/12/2016

Date post:	07-Apr-2017
Category:	Health & Medicine
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Clinical studies and trials on traditional medicine and natural products

Health & Medicine