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Back to the forum  Query: 2017-09-24 14:16 CEST (UTC+2h)
 
M.tareq
Junior

2017-06-27 23:46

Posting: # 17507
Views: 1,460
 

 Paliperidone palmitate IM model effects [Design Issues]

Dear All,

Regarding the Draft Guidance on Paliperidone Palmitate Paliperidone

It states that Both sites of injection (gluteal and deltoid) should be included in the study design for adequate site representation to support the results of the study

That mean, there gonna be an injection site effect in the anova model , sequence*site and subject(Sequence*site ) effects ?

Also regarding sample size for such design suppose a crossover design

The published data suggest an inter-subject variability of 40 - 50 % and no published data on Intra subject variability Xeplion Assessment report
In most cases the inter-subject > intra subject,thus if falsely assuming that the inter = intra That the study gonna be over powered ? how about ethical point and assessor point ?
Or it's more realistic to assume intra = 60 % of the inter variability?
Also about sample size estimation ,will it differ that the study patients gonna be divided into Two groups according to the site of injection ?

Thanks in advance

Best Regards
d_labes
Hero

Berlin, Germany,
2017-06-29 11:05

@ M.tareq
Posting: # 17508
Views: 1,192
 

 Paliperidone palmitate study design

Dear M.tareq,

the Draft Guidance on Paliperidone Palmitate Paliperidone states "Design: Parallel or crossover steady-state".

But: Paliperidone palmitate’s slow dissolution rate results in a half-life of 25 to 49 days. Thus I think a cross-over study isn't really feasible.

Thus go with a parallel-group study. Your doubts about intra-subject variabilities are gone. Use the total variability you have to estimate the sample size.

The evaluation model is then simply an ANOVA with the effects 'treatment' and 'injection site'.

Regards,

Detlew
M.tareq
Junior

2017-06-29 12:47

@ d_labes
Posting: # 17509
Views: 1,180
 

 Paliperidone palmitate study design

Thanks alot Detlew for your reply

Another question does the side of the body mean right or left side of the body will contribute to variability between test to reference? or the model should include another factor for grouping based on right / left side of the body if the subjects were divided into left side injection and right side ? according to spc : alternate injection sites between sides of the body ?

Thanks in advance
d_labes
Hero

Berlin, Germany,
2017-06-30 19:28

@ M.tareq
Posting: # 17510
Views: 1,045
 

 Paliperidone palmitate study design

Dear M.tareq,

» Another question does the side of the body mean right or left side of the body will contribute to variability between test to reference? or the model should include another factor for grouping based on right / left side of the body if the subjects were divided into left side injection and right side ? according to spc : alternate injection sites between sides of the body ?

I don't think so. Sites of injection (gluteal and deltoid) is meant IMHO, and right or left side should not play any role. Alternate injection sites between sides of the body is IMHO meant to protect the participants from local reactions due to too often injections in the same areal.
Or do you expect any differences between left and right side of the body? If yes why? Left and right are categories not known by the treatments to be applied. So why should there differences to be accounted for in the evaluation model?

Regards,

Detlew
M.tareq
Junior

2017-08-07 21:48

@ d_labes
Posting: # 17678
Views: 398
 

 Paliperidone palmitate study design

Sorry for the late reply to your answer,
It was a formal quotation sent to our center by the sponsor suggesting the design mentioned, tried to find some basis for the right /left side of body factor but no justification from their end
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