Ankit Parikh
☆    

India,
2023-06-08 15:54
(179 d 17:54 ago)

Posting: # 23582
Views: 1,138
 

 within subject stan­dard devi­ation in fully repli­cate design if carry over effect is pre­sent [General Sta­tis­tics]

How to calculate within subject standard deviation in fully replicate study design of carry over effect is present?

Eg. I am planning a full replicate single dose study in patients. Patients has to take medication at every 4 month. Pre-dose concentration in subsequent periods are observed below 5 % of Cmax or 0 in pilot study. If carryover effect is present in pivotal study but the pre-dose concentration is less than 5 % of Cmax, how should I calculate Swr for BE assessment?

After dosing, the plasma concentration reaches Cmax in about 4 hours and comes down below 5 % of Cmax in 2-3 days and remains stable from day 4 to 120 and is also the pre-dose concentration for subsequent period/s.

The primary PK parameters are Cmax, AUC0-t and AUC7-t

Thank you for your response in advance.


Edit: Category changed; see also this post #1[Helmut]
dshah
★★  

India/United Kingdom,
2023-06-08 18:35
(179 d 15:13 ago)

@ Ankit Parikh
Posting: # 23583
Views: 963
 

 within subject standard deviation in fully replicate design if carry over effect is present

Hello Ankit!

❝ After dosing, the plasma concentration reaches Cmax in about 4 hours and comes down below 5 % of Cmax in 2-3 days and remains stable from day 4 to 120 and is also the pre-dose concentration for subsequent period/s.


I am not getting you. By 2-3 days, the concentration are below 5% of Cmax and then stable from day 4 to 120?
So by 2-3 days, almost all the drug is eliminated? What is the average half life and range of half life for drug?

Regards,
Divyen
Ankit Parikh
☆    

India,
2023-06-09 09:15
(179 d 00:34 ago)

@ dshah
Posting: # 23584
Views: 839
 

 within subject standard deviation in fully replicate design if carry over effect is present

Hello Divyen!

After dosing, the plasma concentration reaches Cmax in about 4 hours and comes down below 5 % of Cmax in 2-3 days and remains stable from day 4 to 120 and is also the pre-dose concentration for subsequent period/s.

❝ I am not getting you. By 2-3 days, the concentration are below 5% of Cmax and then stable from day 4 to 120?

❝ So by 2-3 days, almost all the drug is eliminated? What is the average half life and range of half life for drug?


Cmax is due to the burst phase of release from the formulation however the plasma concentration required to produce therapeutic effect is very low i.e. < 5 % of Cmax and it remains in therapeutic range from Day 4 to 120 due to slow release of the product. It provides therapeutic effect for 4 months and then new injection has to be taken on day 120.

Regards
Ankit
dshah
★★  

India/United Kingdom,
2023-06-14 11:26
(173 d 22:22 ago)

@ Ankit Parikh
Posting: # 23588
Views: 722
 

 within subject standard deviation in fully replicate design if carry over effect is present

Hello Ankit!

❝ Cmax is due to the burst phase of release from the formulation however the plasma concentration required to produce therapeutic effect is very low i.e. < 5 % of Cmax and it remains in therapeutic range from Day 4 to 120 due to slow release of the product. It provides therapeutic effect for 4 months and then new injection has to be taken on day 120.

This seems to be LAI and from initial post also a HVD?

If by day 4- conc. are LT 5% of Cmax- then what is your half life? Why do you want to measure it for 120 days and the burst release doesn't have any toxicity impact? If even product name can not be shared- then it is difficult to be answered from very few details.

Regards,
Divyen
Ankit Parikh
☆    

India,
2023-06-14 11:33
(173 d 22:16 ago)

@ dshah
Posting: # 23589
Views: 725
 

 within subject standard deviation in fully replicate design if carry over effect is present

Hello Divyen!

❝ ❝ Cmax is due to the burst phase of release from the formulation however the plasma concentration required to produce therapeutic effect is very low i.e. < 5 % of Cmax and it remains in therapeutic range from Day 4 to 120 due to slow release of the product. It provides therapeutic effect for 4 months and then new injection has to be taken on day 120.

❝ This seems to be LAI and from initial post also a HVD?


Yes it is LAI.

❝ If by day 4- conc. are LT 5% of Cmax- then what is your half life? Why do you want to measure it for 120 days and the burst release doesn't have any toxicity impact? If even product name can not be shared- then it is difficult to be answered from very few details.

It is Leuprolide 30 mg 4-month injection. Since it is continuously released and as per OGD, AUC7-t is the primary PK parameter, we need to collect the sample for 112 days. Half-life doesn't matter for this continuous release product.

So how to calculate Swr when unequal carryover effect is present in full replicate study design?

Regads
Ankit
dshah
★★  

India/United Kingdom,
2023-06-14 12:37
(173 d 21:11 ago)

@ Ankit Parikh
Posting: # 23591
Views: 725
 

 within subject standard deviation in fully replicate design if carry over effect is present

Hello Ankit!

As per PSG, the recommendation is parallel study.

[image]

❝ So how to calculate Swr when unequal carryover effect is present in full replicate study design?


Moreover, the study population is patient and you can not stop the treatment. So why fully replicate CO study?

Regards,
Divyen
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