Design and evaluation of bioequivalence

study protocol, study design, parallel and cross over design study

1. DESIGN AND EVALUATION OF BIOEQUIVALENCE STUDY Presented By P. NAGA CHANDRIKA, M. Pharm Research Scholar, Department of pharmaceutics, Geethanjali College of Pharmacy, Hyd

2. ELEMENTS OF STUDY PROTOCOL Title Study objective Study design Study population Clinical procedures Ethical considerations Data analysis Drug accountability Appendix

3. Study Objective To compare the drug bioavailability from test and reference product is not statistically different Same molar concentration Same route of administration

4. Study designs Fasting Study Overnight fasting atleast 10 hours before drug administration 4 hours fasting should be continued after dosing No other medication should be given for atleast 1 week prior to study Food Intervention Study Food + oral drug product Affect bioavailability of drug High fat and high calorie diet given to subjects 30 min before dosing

5. study design

6. Two period cross over design 2 Formulations 2 Groups Latin Square Crossover Design 3 formulations Each formulation administered only once to each subject Period 1 Period 2 Sequence 1 Test Reference Sequence 2 Reference Test Subjects Period 1 Period 2 Period 3 1 A B C 2 B C A 3 C A B

7. Replicate crossover design Four period Two sequence Two formulation Parallel Group Design Two separate groups Drugs – long elimination half life Period 1 Period 2 Period 3 Period 4 Sequence 1 T R T R Sequence 2 R T R T Test product Reference 1 2 3 4 Subjects 5 6 7 8 9 10 11 12

8. Balanced Incomplete Block design Pilot study Subjects Period 1 Period 2 1 A B 2 A C 3 A D 4 B A 5 B C 6 B D 7 C A 8 C B 9 C D 10 D A 11 D B 12 D C

9. Multiple Dose study Cmax : Maximum Drug concentration Cmin : Drug concentration at the end of dosing interval Degree of fluctuation: (Cmax – Cmin) / Cmax Swing: (Cmax – Cmin) / Cmin

10. Drug products Reference product RLD Innovators or original manufacturers brand name product Fully approved NDA Test product Generic product

11. Sample collection Schedule 3 points during absorption phase 3 to 4 at Tmax 4 points during elimination phase

12. Subject Selection Healthy adult volunteers Age 18-45 years Drug use intended in elders (age ≥ 60 years) Women – pregnancy test prior to first dose of study Selection of number of subjects : Pilot studies Previous studies Published data

13. Exclusion criteria Chronic diseases HIV positive Jaundice in past 6 months Psychiatric illness Participated in BABE studies in past 3 months

14. Institutional Review Board

15. Parameters to be measured Pharmacokinetic parameters to be measured are Cmax Tmax AUC Statistical Evaluation Cmax, AUC analysed using ANOVA Tmax analysed by non parametric methods Geometric mean of Cmax t , Cmax r Geometric mean ratio Cmax t/ Cmax r Calculate 90% confidence interval of geometric mean ratio of Cmax

16. To Establish BE The calculated 90% confidence interval for Cmax and AUC should fall within the range 80-125% (Range of bioequivalence ) Non parametric data 90% confidence interval for Tmax should lie with in clinical acceptable range

17. THANK YOU