Clinical studies and trials on traditional medicine and natural products

1. Clinical Studies and Trials on
Traditional Medicine and
Natural Products
Prof. Dr. Basavaraj K. Nanjwade
Department of Pharmaceutics
Rani Chennamma College of Pharmacy,
Belagavi-590010, Karnataka, INDIA.
E-mail: nanjwadebk@gmail.com
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2. The Ultimate Goal
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3. 15/12/2016
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4. Discovery, Design and Development
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5. Medicines research
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6. 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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7. 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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8. Pharmacokinetics
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9. Clinical Studies
• Treatment studies
1. Randomized controlled trial
– Blind trial
– Non-blind trial
2. Adaptive clinical trial
3. 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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10. Clinical Studies
• Observational studies
1. 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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11. 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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12. Steps in Pharmaceutical Products
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13. 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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14. 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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15. 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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16. 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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17. 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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18. 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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19. 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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20. 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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21. 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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22. 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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23. 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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24. 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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25. 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
skills
Patient
monitoring
skills
Physical
assessment
skills
Drug
Information
Skills
Therapeutic
planning
skills
Knowledge
of
nondrug
therapy

28. 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.pd
f
• 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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29. THANK YOU
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2914/12/206
E-mail: nanjwadebk@gmail.com
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