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drmuneesh ★ 2009-08-21 12:59 (6147 d 17:17 ago) Posting: # 4086 Views: 9,045 |
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Dear All I am planning to conduct a bioequivalence study of Rivastigmine Tartrate on 6 mg strength in healthy volunteers. As higher doses may not be tolerated in healthy subjects as nausea, vomiting, and dizziness are the most commonly reported adverse reactions. Some times severe vomiting is associated with oesophageal rupture. According to some literature available on the internet, in which bioequivalence study was done with Rivastigmine Tartrate 6 mg strength with dimenhydinate 75 mg inj I/M given 10 min before dosing and 3 hrs after dosing to prevent nausea and vomiting. But even after concomitant medication there were cases with nausea and vomiting. Please let me know what can be best done to prevent nausea and vomiting. Best Regards Dr Muneesh Garg Edit: Category changed. [Helmut] |
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Helmut ★★★   Vienna, Austria, 2009-08-22 01:17 (6147 d 05:00 ago) @ drmuneesh Posting: # 4091 Views: 8,031 |
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Dear Muneesh, you are sugesting some heavy stuff. ❝ […] literature available on the internet, in which bioequivalence study was done with Rivastigmine Tartrate 6 mg strength with dimenhydinate 75 mg inj I/M given 10 min before dosing and 3 hrs after dosing to prevent nausea and vomiting. But even after concomitant medication there were cases with nausea and vomiting. Horrible. Can you give us this link? ❝ Please let me know what can be best done to prevent nausea and vomiting. No idea. See this thread for a controversial discussion. FDA (draft 04/2009) recommends for the 6 mg strength a study in patients in steady state. FDA also considers the option of a biowaiver (good luck). — 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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drmuneesh ★ 2009-08-22 08:51 (6146 d 21:25 ago) @ Helmut Posting: # 4092 Views: 7,778 |
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Dear Helmut Some of the links are given below. These studies were for european submission. http://www.emea.europa.eu/humandocs/PDFs/EPAR/rivastigmine_teva/H-1044-en6.pdf http://www.emea.europa.eu/humandocs/PDFs/EPAR/nimvastid/H-1029-en6.pdf Regards Muneesh |
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Helmut ★★★ Vienna, Austria, 2009-08-22 15:56 (6146 d 14:21 ago) @ drmuneesh Posting: # 4094 Views: 7,780 |
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Dear Muneesh! Thanks for sharing these references. Very interesting reading matter. Especially the section about PK-interactions. — 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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ElMaestro ★★★ Denmark, 2009-08-22 19:47 (6146 d 10:30 ago) @ drmuneesh Posting: # 4095 Views: 7,781 |
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Dear Muneesh & all, interesting reading in those references. I noticed the following on page 13 in the first Epar: "Hence, it is possible that the observed effect is due solely to chance. The least-squares means of the treatment effect were adjusted for the period effect." In my opinion, the first sentence is an interesting way of saying absolutely nothing. The second sentence is meaningless given the way LSMeans are actually calculated. Makes you wonder, did I skip one of the lectures in statistics?! Best regards EM. |
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Helmut ★★★ Vienna, Austria, 2009-08-22 20:37 (6146 d 09:40 ago) @ ElMaestro Posting: # 4096 Views: 7,732 |
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¡ Hola ElMaestro ! ❝ [...] Makes you wonder, did I skip one of the lectures in statistics?! No, but these guys at EMEA did. When I read the assessment report this morning I couldn't believe it either. But in my experience part of the problem are sponsors's [cough...] 'not so good statisticians' (or CRO's). I have seen many reports were people found a significant treatment of even period [sic!] effect, and wrote lenghty essays in the discussion section that these effects are of no clinical relevance. Maybe EMEA reacts like: 'Ah, very interesting, they have found something and dealt with it. Again (maybe we have readers in London, UK):
— 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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ElMaestro ★★★ Denmark, 2009-08-22 21:17 (6146 d 09:00 ago) @ Helmut Posting: # 4097 Views: 7,684 |
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Ahoy HS, what I meant was that the odd remark about the LS means being adjusted for period effect makes no sense, since this analysis is done with completers only. I think the assessor must have confused it with unbalanced studies where the LSMeans are the raw means adjusted for (averaged over, some would say) different sequence numbers. EM. |
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drmuneesh ★ 2009-08-24 15:59 (6144 d 14:17 ago) (edited on 2009-08-24 16:48) @ ElMaestro Posting: # 4102 Views: 7,634 |
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Dear Helmut and All How can I safely conduct a bioequivalence study of Rivastigmine Tartrate on 6 mg strength in healthy volunteers. Dimenhydrinate injection is not available in India and other drugs effective in preventing nausea and vomiting with cholinesterase inhibitors (rivastigmine) could be ondansetron, glycopyrrolate, trimethobenzamide or trihexyphenidyl as per some literature. But I don't know which one is the best to complete the study safely. Please suggest if anybody has experience of administering Rivastigmine 6 mg in healthy volunteers. Regards Muneesh |
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drcampos ★ Brazil, 2009-08-24 21:26 (6144 d 08:51 ago) @ drmuneesh Posting: # 4103 Views: 7,623 |
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Dear Muneesh, I conducted a bioequivalence study of rivastigmine 6mg in healthy volunteers two months ago. Ondansetron was administered to avoid nausea and vomiting. The administration was done as follows: 4mg in 50mL (infusion of 15 minutes immediatly after the administration of the drug) 2 hours after the administration of the drug (around Cmax/Tmax): 4mg in 100mL (infusion of 30 minutes). Regards, Daniel Rossi de Campos Brazil Edit: Full quote removed. Please delete anything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Helmut] |
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drmuneesh ★ 2009-08-25 08:12 (6143 d 22:04 ago) (edited on 2009-08-25 12:15) @ drcampos Posting: # 4104 Views: 7,558 |
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Dear drcampos Thank you so much for the reply. Can you please tell how many healthy subjects were enrolled in this BE study of Rivastigmine 6mg coadministered with ondansetron and how many subjects suffered from adverse events like nausea and vomiting? And if they had vomiting, was it severe? Any SAEs? Any drop-outs or withdrawals due to AE? If you can please share all this information, this will help me to conduct the study safely and to make all the required arrangements to manage AEs if any. Best Regards Dr Muneesh Garg |
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Dr Lalit ● 2009-08-25 16:41 (6143 d 13:36 ago) @ drmuneesh Posting: # 4111 Views: 7,608 |
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Dear Dr Munish, I have conducted a Pilot BE study on Rivastigmin 6 mg a few years back, hence let me share my experience on this. To tell you in short it's bad... very bad. The drug at that strength causes a lot of AE (Severe Retching with Hot Flushes and dizziness along with palpitation with Tachycardia) in many a subjects thus leading to a series of deviation in the study, since the sample time points are so close. It was quite a problem to tackle all the AE in such a short span of time as all most 30 to 40 % of the subjects were involved (not to forget Oesophageal Rupture that could lead to haemoptysis being at the back of my mind while attending these subjects). It was interesting to note that the other subjects did not have any AE and were quite comfortable at that dose. Regards Dr Lalit Anande |
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drmuneesh ★ 2009-08-26 08:29 (6142 d 21:47 ago) @ Dr Lalit Posting: # 4114 Views: 7,679 |
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Dear Dr Lalit Anande Hi Thank you so much for the response and sharing your experience on rivastigmine 6 mg. Had you given any premedication to the subjects in the study to prevent AEs or it was without premedication? Because without premedication, of course, this drug is very bad. I want to know if we give premedications like ondansetron, then how much AEs can be prevented. Best Regards Muneesh |
Ing. Helmut Schütz