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Lewis Sheiner


2017
Budapest, Hungary



2016
Lisboa, Portugal

2015
Hersonissos, Crete, Greece

2014
Alicante, Spain

2013
Glasgow, Scotland

2012
Venice, Italy

2011
Athens, Greece

2010
Berlin, Germany

2009
St. Petersburg, Russia

2008
Marseille, France

2007
KÝbenhavn, Denmark

2006
Brugge/Bruges, Belgium

2005
Pamplona, Spain

2004
Uppsala, Sweden

2003
Verona, Italy

2002
Paris, France

2001
Basel, Switzerland

2000
Salamanca, Spain

1999
Saintes, France

1998
Wuppertal, Germany

1997
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1996
Sandwich, UK

1995
Frankfurt, Germany

1994
Greenford, UK

1993
Paris, France

1992
Basel, Switzerland



Printable version

PAGE. Abstracts of the Annual Meeting of the Population Approach Group in Europe.
ISSN 1871-6032

Reference:
PAGE 25 (2016) Abstr 5752 [www.page-meeting.org/?abstract=5752]


Oral: Other Topics


B-19 Rik Schoemaker Extrapolation of a Brivaracetam Exposure-Response Model from Adults to Children

Rik Schoemaker(1,3), Armel Stockis(2)

(1) SGS Exprimo, (2) UCB Pharma, (3) Current affiliation: Occams

Objectives: To scale an existing adult population PK/PD model for brivaracetam (BRV) into children, using a combined adult-pediatric PK/PD model for levetiracetam (LEV), a compound with a similar primary mechanism of action, and to predict the effective dose of BRV in children aged 4 to 16 years.

Methods: A population PK/PD model has been previously developed to describe the relationship between BRV plasma concentrations and seizure frequency change from baseline in adult subjects. A pediatric population PK model is available for BRV. For LEV, both PK and PD data are available in adults and children. In order to support the extrapolation of PD in BRV to children aged ≥4 to

The model described seizure counts using a negative binomial distribution taking previous day seizure frequencies into account [1], and using a mixture model to separate a 'placebo like' and a 'responder' sub-population. 

VPCs were used to ascertain the ability of the LEV adult/pediatric PK/PD model to adequately simulate trial outcome in terms of percentage change in seizure frequency from baseline, and fraction of subjects with ≥50% decrease in seizure frequency. PK and PD simulations for BRV were performed in children for a range of mg/kg doses to predict BRV effect in pediatric subjects, and aid trial design decisions.

Results: The LEV PK/PD model was able to describe both the adult and the pediatric data using the same drug effect population parameters, and using a model structure very similar to the existing adult PK/PD BRV model. VPCs illustrated that the LEV adult/pediatric PK/PD model was capable of simulating the observed trial outcomes. Simulation with the adult BRV PK/PD model in combination with the pediatric BRV population PK model, allowed characterization of the dose-response curve, suggesting maximum reponse at BRV 4 mg/kg/day dosing in children.

Conclusions: Application of a population PK/PD count model to trial data from a registered compound with a similar primary mechanism of action, allowed prediction of drug effects in pediatric patients for BRV that will help plan future studies.



References:
[1] Ahn JE, Plan EL, Karlsson MO and Miller R. Modeling Longitudinal Daily Seizure Frequency Data From Pregabalin Add-On Treatment. J Clin Pharmacol 2012 52: 880-892.