hirenpharm ☆ Ahmedabad, 2019-03-29 21:56 (2019 d 16:20 ago) Posting: # 20103 Views: 5,283 |
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Hello everyone, We did a multiple dose (5 weeks, 1 TDS patch every week) bioequivalence study. The BE was assessed at week 5 at steady state. It was a 3-period study. In period 2 and 3, we observed some carry-over from the previous period treatments. I remember, the 5% of Cmax rule for single-dose studies. But, can someone please throw some light on how to handle this carry-over in multiple dose steady state studies? Does the carry-over in week 1 pre-dose really impact week 5 steady state parameters? any regulatory guidance/published articles will be really helpful. Edit: Category changed; see also this post #1. [Helmut] — Dr. Hiren Mehta |
Nirali ★ India, 2019-03-30 08:20 (2019 d 05:56 ago) @ hirenpharm Posting: # 20104 Views: 4,415 |
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Hello Hiren, Is this patient study or healthy Volunteer study? — Nirali Mehta (PHARMA-STATS) |
Helmut ★★★ Vienna, Austria, 2019-03-31 16:52 (2017 d 22:24 ago) @ hirenpharm Posting: # 20107 Views: 4,437 |
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Hi Hiren, please see this post (#3 and #5). Without knowing the regulation you are bound to and more details about the study we are fishing in the dark. ❝ We did a multiple dose (5 weeks, 1 TDS patch every week) bioequivalence study. The BE was assessed at week 5 at steady state. It was a 3-period study. In period 2 and 3, we observed some carry-over from the previous period treatments. I remember, the 5% of Cmax rule for single-dose studies. Correct (EMA, FDA). Equal carry-over does not bias the estimated treatment effect, whereas unequal carry-over will (to an unknown degree). Since no statistical method exists to correct the later, it has to be avoided by design (in SD sufficiently long washout or – in the case of steady state / switch-over – washout from one treatment overlapping built-up of steady state of the other). ❝ But, can someone please throw some light on how to handle this carry-over in multiple dose steady state studies? Since you mentioned steady state, I assume relevant accumulation (otherwise, f.i. according to the EMA’s GL the multiple dose study can be waived). By definition (superposition principle of linear PK) you will observe residual concentrations from earlier doses. Hence, the exclusion-rule does not make any sense. I hope you didn’t state it in the protocol. ❝ Does the carry-over in week 1 pre-dose really impact week 5 steady state parameters? Don’t understand what you mean. @Nirali: Why should that matter? — 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 |
Nirali ★ India, 2019-04-03 04:48 (2015 d 10:28 ago) @ Helmut Posting: # 20116 Views: 4,263 |
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@Helmut, To know more about study design & wash out Period. — Nirali Mehta (PHARMA-STATS) |
jag009 ★★★ NJ, 2019-04-02 19:46 (2015 d 19:30 ago) @ hirenpharm Posting: # 20115 Views: 4,240 |
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Hi, ❝ We did a multiple dose (5 weeks, 1 TDS patch every week) bioequivalence study. The BE was assessed at week 5 at steady state. It was a 3-period study. In period 2 and 3, we observed some carry-over from the previous period treatments. Did you achieve steady state in all three treatments? |