Partial AUC & Cmax in case of multiphasic modified release drug product [Regulatives / Guidelines]
Dear All,
I wish to conduct a 2-way crossover study on multiphasic modified release drug product for EMEA submission.
The drug product is a prolonged release formulation with biphasic release pattern (IR+MR). The initial maximum concentration achieves at about 1 to 2 hours (due to release of IR Part) and Peak plasma concentration achieves at about 6 to 8 hours.
As per "Guideline on the pharmacokinetic and clinical evaluation of modified release dosage forms_Jun-2015", For single dose study of multiphasic modified release drug product following parameters has to show bioequivalence.
AUC0-t, AUC0-∞, partialAUCs and Cmax in all phases.
I have kept AUC0-t, AUC0-∞, partialAUC0-2, partialAUC2-t.
Please provide your opinion on following points.
(1) Please help to understand the meaning of "Cmax in all phases".
Shall I consider it as Cmax(0-2) & Cmax(2-t)? OR shall I consider Cmax(0-t)?
Shall I report the result for Cmax(0-2) & Cmax(2-t) and prove bioequivalence only on Cmax(0-t)?
(2) As per the guideline, Cmax(x+1) and partialAUC(x+1) also need to be evaluated. In this case shall I consider it as Cmax(2+1) = Cmax0-3 & partialAUC(2+1) = partialAUC(0-3)? Please help to understand the rationale of Cmax(x+1) & partialAUC(x+1).
Thanks in advance.
I wish to conduct a 2-way crossover study on multiphasic modified release drug product for EMEA submission.
The drug product is a prolonged release formulation with biphasic release pattern (IR+MR). The initial maximum concentration achieves at about 1 to 2 hours (due to release of IR Part) and Peak plasma concentration achieves at about 6 to 8 hours.
As per "Guideline on the pharmacokinetic and clinical evaluation of modified release dosage forms_Jun-2015", For single dose study of multiphasic modified release drug product following parameters has to show bioequivalence.
AUC0-t, AUC0-∞, partialAUCs and Cmax in all phases.
I have kept AUC0-t, AUC0-∞, partialAUC0-2, partialAUC2-t.
Please provide your opinion on following points.
(1) Please help to understand the meaning of "Cmax in all phases".
Shall I consider it as Cmax(0-2) & Cmax(2-t)? OR shall I consider Cmax(0-t)?
Shall I report the result for Cmax(0-2) & Cmax(2-t) and prove bioequivalence only on Cmax(0-t)?
(2) As per the guideline, Cmax(x+1) and partialAUC(x+1) also need to be evaluated. In this case shall I consider it as Cmax(2+1) = Cmax0-3 & partialAUC(2+1) = partialAUC(0-3)? Please help to understand the rationale of Cmax(x+1) & partialAUC(x+1).
Thanks in advance.
Complete thread:
- Partial AUC & Cmax in case of multiphasic modified release drug productmaulik963 2016-05-31 08:09 [Regulatives / Guidelines]
- The x unveiled Helmut 2016-05-31 13:14
- The x unveiled maulik963 2016-06-02 13:45
- Biphasic: x=2 Helmut 2016-06-02 14:07
- The x unveiled maulik963 2016-06-02 13:45
- The x unveiled Helmut 2016-05-31 13:14