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hiren379 ★ India, 2012-12-11 06:31 (4945 d 17:51 ago) Posting: # 9706 Views: 4,762 |
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Hello All, We are planning pivotal biostudy for one of the highly variable molecule (DR Formulation). We have conducted pilot Ref-replicated biostudy, but were suprised with few observations... 1) Inspite of >35 samples we got last point Cmax in 4 subjects in Reference arm:confused 2) After 3-4 zero concentrations in some subjects, we are getting Cmax immediately in next time point. This is similar to first point Cmax. 3) We got just 2 non zero concentrations in 4 subjects and 3 non zero concentrations in 3 subjects in Reference arm. Concentrations are rising and falling very sharply. :  We are planning to keep an exclusion criteria in our Pivotal study like. Subjects having minimum of 4 non zero concentrations will be included in the study if first and last points are not Cmax. Please guide on regulatory acceptability (particularly for USFDA) of such criterion. If this can be handeled with some other criteria, please suggest... |
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drgunasakaran1 ★★  2012-12-11 06:53 (4945 d 17:29 ago) @ hiren379 Posting: # 9707 Views: 4,131 |
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Dear Mr Hiren, ❝ We are planning pivotal biostudy for one of the highly variable molecule (DR Formulation). Are you dealing with Bisphophanates (Risendronate sodium 35 mg DR tablets)? ❝ 1) Inspite of >35 samples we got last point Cmax in 4 subjects in Reference arm Check the literature of the drug, if the range of Tmax of your drug is very high and make sure that you didn't captured the sampling time points based on the Median Tmax rather than the Range. ❝ 2) After 3-4 zero concentrations in some subjects, we are getting Cmax immediately in next time point. This is similar to first point Cmax. If the drug has rapid distribution phase simiar to Risedronate, you may get profile like this. ❝ 3) We got just 2 non zero concentrations in 4 subjects and 3 non zero concentrations in 3 subjects in Reference arm. Concentrations are rising and falling very sharply. To avoid this, you should have very frequent sampling time points in the Tmax Range. ❝ Please guide on regulatory acceptability (particularly for USFDA) of such criterion. In my personal opinion, regulatory may not accept this procedure. — Dr Gunasakaran Sambandan MD Disclaimer: The replies/posts are my personal opinions, and they do not represent my company's views on the same. LinkedIn |
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hiren379 ★ India, 2012-12-11 07:03 (4945 d 17:19 ago) @ drgunasakaran1 Posting: # 9708 Views: 4,035 |
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❝ Check the literature of the drug, if the range of Tmax of your drug is very high and make sure that you didn't captured the sampling time points based on the Median Tmax rather than the Range. Sampling time points were optimised based on all available literature to capture Cmax ❝ If the drug has rapid distribution phase simiar to Risedronate, you may get profile like this. Rapid distribution is not reported. In other subjects such behaviour is not observed If you have any other idea to tackle such situation please let me know .... |
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drgunasakaran1 ★★ 2012-12-11 10:02 (4945 d 14:20 ago) @ hiren379 Posting: # 9709 Views: 3,980 |
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Dear Mr Hiren, ❝ Rapid distribution is not reported. In other subjects such behaviour is not observed. Since the drug is highly variable in nature, you may not get similar profile or behavior in other subjects. Kindly look into the nature of variability of the drug, whether the variability is in the Absorption or Distribution phase or in Metabolism. — Dr Gunasakaran Sambandan MD Disclaimer: The replies/posts are my personal opinions, and they do not represent my company's views on the same. LinkedIn |
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