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kaushik089 ★ India, 2012-06-22 15:33 (4706 d 22:56 ago) Posting: # 8825 Views: 5,380 |
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Hello all, Good Evening, My question is when we are administering a dose which is a tablet that has to be taken with some applicable amount of drinking water then what if the subject chewed the tablet instead of swallowing it? Can we continue the subject in the study or not?? will it impact the Pk parameters? kind regards, kaushik panigrahi. Edit: Category and subject line changed; please don’t post everything in the Regulatives / Guidelines category. [Helmut] |
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Helmut ★★★   Vienna, Austria, 2012-06-22 17:22 (4706 d 21:08 ago) @ kaushik089 Posting: # 8826 Views: 4,582 |
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Dear Kaushik! ❝ My question is when we are administering a dose which is a tablet that has to be taken with some applicable amount of drinking water then what if the subject chewed the tablet instead of swallowing it? The protocol should state how the formulations are administered. The protocol should refer to posology given in the label/SmPC of the reference and the IMPD/IB of the test product. If nothing specific is given I would assume the worst case “must be swallowed unchewed as a whole”. ❝ will it impact the Pk parameters? Even if nothing specific is stated in the label/SmPC and/or IMPD/IB you should not assume that absorption will not be influenced. Expect are more pronounced effect for all types of MR products. For delayed release you can expect serious dose dumping (product behaves like an IR formulation) or very low / no concentrations at all if the API is susceptible to degradation in the acidic environment of the stomach. For CR you can expect faster absorption – though not necessarily complete dose dumping. ❝ Can we continue the subject in the study or not?? Given the above (and assuming you have stated nothing in the protocol) I would write an amendment or at least a note to file stating that the subject will be taken out from the confirmatory assessment of bioequivalence. You can present the complete data set (with the subject) in an exploratory manner. Personally I would assume the worst case scenario and take the subject out (no further dosing, but samples analyzed). — 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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ElMaestro ★★★ Denmark, 2012-06-22 17:43 (4706 d 20:46 ago) @ Helmut Posting: # 8827 Views: 4,498 |
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Hi HS, ❝ Given the above (and assuming you have stated nothing in the protocol) I would write an amendment or at least a note to file stating that the subject will be taken out from the confirmatory assessment of bioequivalence. You can present the complete data set (with the subject) in an exploratory manner. Personally I would assume the worst case scenario and take the subject out (no further dosing, but samples analyzed). Are you sure about this? If nothing is written in the protocol about excluding those who chew, and everything else is done according to SOPs then I would think:
— Pass or fail! ElMaestro |
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Helmut ★★★ Vienna, Austria, 2012-06-22 18:00 (4706 d 20:30 ago) @ ElMaestro Posting: # 8828 Views: 4,606 |
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Hi ElMaestro! ❝ ❝ Given the above (and assuming you have stated nothing in the protocol) I would write an amendment or at least a note to file stating that the subject will be taken out from the confirmatory assessment of bioequivalence. You can present the complete data set (with the subject) in an exploratory manner. Personally I would assume the worst case scenario and take the subject out (no further dosing, but samples analyzed). ❝ ❝ Are you sure about this? I’m never sure (some kind of professional deformation).  ❝ If nothing is written in the protocol about excluding those who chew, and everything else is done according to SOPs then I would think: ❝ 1. The subject fulfils the PP and ITT criteria. Agree. ❝ 2. The subject should not be eliminated from analysis or terminated from study, at least as long as the chewing does not cause safety concerns. Well. If the posology does not specifically state that chewing is allowed, I would assume the worst. I would not expect a large impact on IR formulations but MR are of a different breed. If the subject is kept in the data set (following the protocol) this may blew the study. I would rather follow common sense: “Oops, the volunteer chewed the tablet – we haven’t thought about that – might have an impact on absorption – do we want to compare e.g. Testchewed vs. Referenceunchewed? – write an amendment.” ❝ 3. The clinic should update SOPs so that this doesn't happen in the future. Agree. — Dif-tor heh smusma 🖖🏼 Довге життя Україна! Helmut Schütz The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |
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jag009 ★★★ NJ, 2012-06-22 22:16 (4706 d 16:13 ago) @ Helmut Posting: # 8830 Views: 4,511 |
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Hi Helmut, If subject is kept, you can submit 2 sets of results no? One with and one without that subject and document it? John |
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Helmut ★★★ Vienna, Austria, 2012-06-23 14:41 (4705 d 23:49 ago) @ jag009 Posting: # 8833 Views: 4,484 |
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Hi John! ❝ If subject is kept, you can submit 2 sets of results no? One with and one without that subject and document it? Yes you can. I prefer to make clear (before running the actual analyses) which data set will be the primary one. Avoids cherry-picking discussions.  — Dif-tor heh smusma 🖖🏼 Довге життя Україна! Helmut Schütz The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |
Ing. Helmut Schütz