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sudy ☆ India, 2018-03-28 09:09 (2546 d 06:39 ago) Posting: # 18598 Views: 4,125 |
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Dear all, I have a discussion point regarding switchability criteria for methylphenidate 54mg tabs (specially). For lower strength, they have removed this criterion. As per guideline, we have to meet the ABE criteria and additionally meet 95% UB for switchability. Now, as we are doing a fully replicate study as suggested by OGD recommendation on methylphenidate, can we use RSABE approach in case if we get ISCV-reference > 30% for any one of the PK parameter Cmax or partial AUCs, instead of using 90% CI calculation to prove the bioequivalence? The OGD recommendation did not discuss anything about this case, as we know that methylphenidate is not a HVD. But incase if we got CV-R more than 30%, can we apply RSABE? Your suggestion will be highly appreciated. Regards, Sudy |
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Helmut ★★★   Vienna, Austria, 2018-03-28 13:25 (2546 d 02:23 ago) @ sudy Posting: # 18599 Views: 3,662 |
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Hi sudy, ❝ […] can we use RSABE approach in case if we get ISCV-reference > 30% for any one of the PK parameter Cmax or partial AUCs, instead of using 90% CI calculation to prove the bioequivalence? The guidance clearly states: The 90% confidence intervals of the geometric mean test/reference (T/R) ratios for the above five Cmax and AUC metrics (Cmax, AUC0-T1, AUCT1-T2, AUCT2-T3, AUC0-∞) should fall within the limits of 80-125%. Without a controlled correspondence you will risk an RTR because according to
❝ The OGD recommendation did not discuss anything about this case, as we know that methylphenidate is not a HVD. In my experience you will get the highest CV in the first partial AUC of the fasting study. I never saw a high CV of Cmax… A CVwR >30% of AUC0-3 is extremely unlikely. @John: Other experiences? — Dif-tor heh smusma 🖖🏼 Довге життя Україна! ![[image]](https://static.bebac.at/pics/Blue_and_yellow_ribbon_UA.png) Helmut Schütz ![[image]](https://static.bebac.at/img/CC by.png) The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |
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sudy ☆ India, 2018-03-28 14:13 (2546 d 01:36 ago) @ Helmut Posting: # 18600 Views: 3,516 |
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Dear Helmut, Thanks for your reply. Regards, sudy |
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jag009 ★★★ NJ, 2018-03-28 23:35 (2545 d 16:14 ago) @ Helmut Posting: # 18608 Views: 3,489 |
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Hi Helmut! ❝ In my experience you will get the highest CV in the first partial AUC of the fasting study. I never saw a high CV of Cmax… A CVwR >30% of AUC0-3 is extremely unlikely. ❝ ❝ @John: Other experiences? Yes the culprit is the first partial AUC. However, if the coating on your delayed release bead is acting funny then it's possible for you to see high CV on the 1st and 2nd partial AUCs... John |
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jag009 ★★★ NJ, 2018-03-28 23:33 (2545 d 16:16 ago) @ sudy Posting: # 18607 Views: 3,461 |
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❝ Now, as we are doing a fully replicate study as suggested by OGD recommendation on methylphenidate, can we use RSABE approach in case if we get ISCV-reference > 30% for any one of the PK parameter Cmax or partial AUCs, instead of using 90% CI calculation to prove the bioequivalence? Yes. Reason is that it is possible for one of those PK parameters to show ISCV > 30%. As an added bonus, even if a BE guidance states that crossover studies are required but you have data to support that the drug of interest is HVD (ISCV>30%, provided that the high ISCV is not because your formulation is crap) then you can run the studies as replicates. I have done 2 projects in the past already. P.S. You woke me up from my hibernation Helmut...  John |
Ing. Helmut Schütz