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jag009 ★★★ NJ, 2012-04-12 20:11 (5190 d 21:29 ago) Posting: # 8416 Views: 5,766 |
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Hi everyone, Is 36 hour sampling sufficient for a single dose Metadate CD? I checked literature and the t1/2 was about 6.4 ± 1.4. Pentikis HS, Simmons RD, Benedict MF, and SJ Hatch Methylphenidate Bioavailability in Adults When an Extended-Release Multiparticulate Formulation Is Administered Sprinkled on Food or as an Intact Capsule J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 41:4, APRIL 2002, 443–9 Thanks John Edit: Authors added to reference. [Helmut] |
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Helmut ★★★   Vienna, Austria, 2012-04-12 20:45 (5190 d 20:55 ago) @ jag009 Posting: # 8417 Views: 5,112 |
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Hi John! ❝ Is 36 hour sampling sufficient for a single dose Metadate CD? I checked literature and the t1/2 was about 6.4 +/- 1.4. 24 hours are long enough to cover >80% of AUC∞. Rochdi et al. (2004)* investigated Metadate CD 10, 20, 30 mg and found (n=23): 10 mg 20 mg 30 mgCVs were 11.8% for Cmax, 7.7% for AUCt, and 7.6 for AUC∞. I wouldn’t recommend a sample size of >16 subjects. If you want to be on the safe side opt for a Two-Stage Design (accepted by FDA, HPB, and EMA).
— 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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jag009 ★★★ NJ, 2012-04-13 01:44 (5190 d 15:55 ago) @ Helmut Posting: # 8418 Views: 5,026 |
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Thanks Helmut :) |
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Helmut ★★★ Vienna, Austria, 2012-04-13 02:43 (5190 d 14:56 ago) @ jag009 Posting: # 8419 Views: 5,046 |
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Hi John, I forgot: Pentikis et al. (2002) sampled also for 24 hours; the mean AUCt/AUC∞-ratio was 91.4%. I guess that their LLOQ of 250 pg/mL was insufficient to measure concentrations at 24 hours in many subjects. For a 20 mg dose you should aim at an LLOQ of ~50–100 pg/mL. CVs were 9.92% (Cmax), 6.48% (AUCt), and 5.79% (AUC∞). All studies on MR MPH I know of sampled for 24 hours – some studies on IR MPH only 16 hours. I don’t have the slightest idea why some people* performed studies of a drug with so little intra-subject variability in 36 subjects (even CV of AUC0-4 was only 13.5%).  Power for CV 15% and T/R 95% is 83% in just 12 subjects.
— 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, 2012-04-13 17:59 (5189 d 23:41 ago) @ Helmut Posting: # 8420 Views: 4,967 |
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Hi Helmut, It's Friday!   ❝ I don’t have the slightest idea why some people* performed studies of a drug with so little intra-subject variability in 36 subjects (even CV of AUC0-4 was only 13.5%). ❝ Power for CV 15% and T/R 95% is 83% in just 12 subjects. I guess it's a comfort factor for them in case something does happen during the study and more than half the subjects went wazoo (food poisoning or others..). We need at least n=12 to submit... I ran a study in my previous company with 36 subjects and 18 subjects were removed from the study due to food poisoning in the clinic (post dose, not sure if it was really food poisoning since the other subjects were fine).  We ended up submitting the study results with 17 subjects (1 quit)... |
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Helmut ★★★ Vienna, Austria, 2012-04-13 18:17 (5189 d 23:22 ago) @ jag009 Posting: # 8421 Views: 5,169 |
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Hi John! ❝ It's Friday! Still smoking in the US?! ❝ […] in case something does happen during the study and more than half the subjects went wazoo (food poisoning or others..). We need at least n=12 to submit... I ran a study in my previous company with 36 subjects and 18 subjects were removed from the study due to food poisoning in the clinic (post dose, not sure if it was really food poisoning since the other subjects were fine). Wow, that’s a weird story. According to ICH-E9 we have to justify the sample size (not to speak about ICH-E6 and ICH-E8). FDA wants us to plan a BE study with a power of 80–90%. It’s the job of the IEC to protect the safety of subjects. If they are compos mentis they should reject a study planned with a power of 99.92% (CV 15%, T/R 95%, n=36) with a justification like “there might be ⅔ dropouts resulting in 83% power with n=12”. — 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, 2012-04-13 18:35 (5189 d 23:04 ago) @ jag009 Posting: # 8422 Views: 6,159 |
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Hi jag009, In contrast to HS I think everything is fine here. I mean if you are going to give a buncha volunteers food poisoning then, heck, including 36 and sending half of them home (with a buncha free toilet rolls having the CROs logo on each leaf?) due to food poisoning then it means you're having a little buffer of 6 subjects for eventualities. That all in all sounds just about right to me. I wish you all a good weekend. — Pass or fail! ElMaestro |
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jag009 ★★★ NJ, 2012-04-18 17:57 (5184 d 23:43 ago) @ Helmut Posting: # 8442 Views: 4,867 |
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Hi Helmut, Is Methylphenidate light sensitive and that the bioanalytical lab needs to be UV light filtered (similar to Nifedipine?). Thanks John |
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ElMaestro ★★★ Denmark, 2012-04-18 18:35 (5184 d 23:04 ago) @ jag009 Posting: # 8443 Views: 4,815 |
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Hi Jag009, ❝ Is Methylphenidate light sensitive and that the bioanalytical lab needs to be UV light filtered (similar to Nifedipine?). As far as I know there's no real light sensitivity with this API. But it not entirely uncommon that patients on methylphenidate become a bit photophobic. So if your lab technicians are on Ritalin it wouldn't hurt to turn down the lights a bit or to hand out sunglasses  — Pass or fail! ElMaestro |
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jag009 ★★★ NJ, 2012-04-18 19:09 (5184 d 22:31 ago) @ ElMaestro Posting: # 8444 Views: 4,799 |
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Thanks Elmaestro, I confirmed with my lab people on the API as well.  |
Ing. Helmut Schütz