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ClinResBE ☆ India, 2014-03-05 18:33 (4493 d 10:02 ago) Posting: # 12564 Views: 3,416 |
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Dear all, We are doing a BE pivotal study for a drug which has half life of 18-44 h. Per protocol, study design is two way crossover and sample size is 46. Per literature, drug is metabolised by cytochrome P450 isoenzyme P450 2D6, and 3 – 10 % of the population has reduced isoenzyme activity (poor metabolisers). Could you kindly let me know: 1) Is two way crossover the appropriate design or do you recommend parallel design for this drug which has a maximum half life of 44 h? 2) What is the cut-off half life limit to select parallel design? Regulatory guidance mentions that appropriate design for the drugs with long half-life is parallel design, but I could not find any cut-off limit for half life in any regulatory guidance document. 3) As parallel design needs twice as many number of subjects relative to crossover design, is the cost factor also a criteria for selecting an appropriate design? 4) Can our study be conducted in cohorts by having a protocol amendment in place as it seems CRO cannot enroll the required number of subjects who are eligible in one go. My concern is, as already drug has a problem of poor metabolisers in community, doing the study in cohorts will increase the variabilty further during final analysis, which may affect study outcome adversely. Thank you so much. Kind regards Max |
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Dr_Dan ★★ Germany, 2014-03-06 12:37 (4492 d 15:58 ago) @ ClinResBE Posting: # 12569 Views: 2,770 |
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Dear Max There is no cut-off half life limit to select a parallel design. In your case proceed with a two way crossover design. A maximum half life of 44 h would lead to a wash out of 14 days (or even less since this is more than 7 times thalf). A wash out period of 14 days is very common in standard bioequivalence studies. Per protocol, your study design is two way crossover and sample size is 46. If you can not recruit 46 subjects at once you have to conducted the study in cohorts and you do not necessarily need to prepare a protocol amendment. If your study conduct is standardised and the conditions are the same for both (all) subject groups then this will not affect study outcome adversely since the intra-subject (!) variabilty should not increase. I hope this helps Kind regards Dr_Dan — Kind regards and have a nice day Dr_Dan |
Ing. Helmut Schütz