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The following message was posted to: PharmPK
Dear all,
I have a question regarding dosing strategy of a monoclonal antibody
in early clinical development and I would highly appreciate to hear
your expert opinion on this. We are planning the early clinical
development of a monoclonal IgG antibody targeting a soluble antigen
and the route of administration in clinical trials is first iv and
later on subcutanously. Would you suggest to start with a fixed dosing
schedule (every subject gets the same amount of dose) or with a
normalized dosing schedule? In case of normalization, would you use
body weight or BSA? What is the scientific rationale to go with a Body
weight or BSA normalized dosing strategy? Chee Ng and colleagues have
performed Pop-PK studies with rituximab in rheumatoid arthritis (J
Clin Pharmacol. 2005 Jul;45(7):792-801) and with pertuzumab in cancer
patients (Pharm Res. 2006 Jun;23(6):1275-84. Epub 2006 May 26)
demonstrating the feasibility of fixed dosing strategy for these two
mAbs. Are these two studies representative for mAbs or would you think
that in most cases body weight and/or BSA are significant covariates
explaining variability in PK?
Looking forward to your responses.
Regards
Tine
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The following message was posted to: PharmPK
my experience with MAbs is dosing on BW basis and perhaps moving to a
fixed dose later in clinical development....
Jeffrey L. Larson, Ph.D., DABT
President
Parady Consulting Inc.
2314 Acadiana Lane
Seabrook, TX 77586
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Hi,
In my experience dosing is per kg bw, intitially one subject on the
first day then another and then the third (making sure that at most
one of those three is placebo), and then the rest of the subjects for
that dose level together on one day. Search the web for Minimum
Anticipated Biological Effect Level.
See for instance:
http://www.abpi.org.uk/information/pdfs/Expert-trials-Consultation14Sep06.pdf
Frieda Ebes
Kendle International B.V.
the Netherlands
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