Bioequivalence and Bioavailability Forum

Dear Heema!

❝ [...] based on current guideline (CPMP/EWP/280/96), total three studies are

❝ recommended 1) single dose fast, 2) single dose fed and 3) multiple dose

❝ steady state.

❝

❝ The reference listed drug is recommended with meal as a bid regimen. Also,

❝ it is reported that there is no food effect on bioavailability of this drug.

1) to 3) is correct for prolonged release formulations (Section 5.1 and Appendix 1; Data indicating no food effect). Not sure if 3) is necessary for delayed release formulations (Section 5.2) - but in the past regulators routinely asked for multiple dose studies of this MR type as well.

❝ Now my question is: should we conduct a steady state study under fed

❝ state or fasted state?

Since there is no indication of a food effect and the innovator labeled the formulation to be administered with food, I would say there could be some reasons not connected with PK, e.g. gastrointestional disturbances or other AEs. The single dose study fasting should be the most discriminatory one, anyhow. If my assumptions about AEs are correct, I would consider it unethical to perform the multiple dose study fasting (against the SmPC).
Interested in other opinions.