1. Clinical Trials - PHASE II

2. Introduction  Important part of drug discovery process  Why important??  Therapeutic exploratory trial  First time in patients

3. OBJECTIVES Efficacy in patients  Pharmacodynamic action 2. Safety issues  Common short term side effects

4. OBJECTIVES 3. Optimum dose finding  Dose efficacy relationship  Therapeutic dose regimen  Duration of therapy  Frequency of administration  Therapeutic window

5. OBJECTIVES 4. Define target patient population  Types of patients with specific indication 5. Evaluation of potential study points  Measurement of efficacy 6. Idenditify the promising drug candidate

6. SUBDIVISION OF PHASE II A. Phase II a  Pilot clinical trial B. Phase II b  Pivotal clinical trial

7. PHASE II a PILOT CLINICAL TRIAL  Small scale  Often unblind and open label  Intended to provide experience to investigator  Feasibility trial

8. PILOT CLINICAL TRIAL OBJECTIVES 1. To confirm that trial medicine, procedure are safe, suitable, and operational. 2. Dose range of new drug 3. Initial efficacy evaluation of a new drug, or for new indication 4. Determine the duration required

9. PILOT CLINICAL TRIAL OBJECTIVE 5. Evaluation of variables related to clinical pharmacology 6. Estimation of required sample size 7. For evaluation of methodology 8. Determination of availability of patient 9. Exploration of ethical questions

10. PHASE II b PIVOTAL CLINICAL TRIAL  Well planned, well controlled trial, in full scale  Most rigorous demonstration of drug efficacy  Conducted in units with specialist investigators with experience of particular indication  Adequate investigational facilities to monitor safety and efficacy  Doses are usually less than the highest doses used in phase I

11. PHASE II b PIVOTAL CLINICAL TRIAL  Usually, only 3-4 centers are included  Normally, 10-12 patients should be studied at each dose-level  May or may not randomized  Open or double blinded trial  Placebo or comparator controlled  Further evaluation of safety, pharmacokinetic data

12. SUBJECT REQUIREMENTS  Approximately 50-300 patients required  Narrow inclusion criteria  Homogenous population  Preferably not suffering from confounding comorbities DURATION Commonly takes 2-3 years

13. REGULATORY REQUIREMENTS  Phase I and Preclinical studies must be completed before commencing phase II trial -FDA  Scheduled meeting at the end of phase II with FDA  Permission from DCGI before Phase II  Fee 25,000 at DCGI

14. Journey to cover  Phase III trial