hirenpharm
☆    

Ahmedabad,
2019-03-29 19:56

Posting: # 20103
Views: 396
 

 Carry-over in pre-dose samples for steady state BE [Study As­sess­ment]

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 06:20

@ hirenpharm
Posting: # 20104
Views: 346
 

 Carry-over in pre-dose samples for steady state BE

Hello Hiren,
Is this patient study or healthy Volunteer study?

Nirali Mehta
(PHARMA-STATS)
Helmut
★★★
avatar
Homepage
Vienna, Austria,
2019-03-31 12:52

@ hirenpharm
Posting: # 20107
Views: 300
 

 5% Cmax-rule only in SD

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?

Cheers,
Helmut Schütz
[image]

The quality of responses received is directly proportional to the quality of the question asked. ☼
Science Quotes
Nirali
★    

India,
2019-04-03 00:48

@ Helmut
Posting: # 20116
Views: 202
 

 5% Cmax-rule only in SD

@Helmut, To know more about study design & wash out Period.

Nirali Mehta
(PHARMA-STATS)
jag009
★★★

NJ,
2019-04-02 15:46

@ hirenpharm
Posting: # 20115
Views: 215
 

 Carry-over in pre-dose samples for steady state BE

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?
Activity
 Thread view
Bioequivalence and Bioavailability Forum |  Admin contact
19,400 posts in 4,121 threads, 1,323 registered users;
online 6 (0 registered, 6 guests [including 4 identified bots]).
Forum time (Europe/Vienna): 18:53 UTC

Science is the great antidote to the poison
of enthusiasm and superstition.    Adam Smith

The BIOEQUIVALENCE / BIOAVAILABILITY FORUM is hosted by
BEBAC Ing. Helmut Schütz
HTML5