Developing an Adaptive Trial Design that Accounts for Rapidly Changing Pediatric Physiology

On-Demand Webinar

Mother-to-child HIV transmission (MTCT) is a public health issue in low-resource countries. Prophylactic treatment of newborns shortly after birth is critical to prevent MTCT. Raltegravir is an antiretroviral agent which blocks a critical step in the virus lifecycle―integration of viral DNA into the host cell. Currently, this drug is only approved for treating infants at least 4 weeks old.

In this webinar, we discussed a population pharmacokinetic modeling and simulation approach to design a raltegravir dosing regimen for the prevention or treatment of HIV in newborns up to 6 weeks of age. Raltegravir is metabolized via UGT-1A1. Therefore special attention will be given to the extreme UGT-1A1 enzyme maturation profile which is almost inactive at birth and becomes fully mature after about 6 months. Also, absorption appears to become more efficient during the first days of life. Furthermore, we will show how allometric scaling was used to account for significant body weight changes of neonates.

This work is part of a two-step adaptive trial design. Data from the first cohort was used to inform the neonate pharmacokinetic model. Simulations based on this model provided the basis for selecting a dosing regimen for neonates of the second cohort of the ongoing trial.

About Our Speaker

Webinar-1speaker-LommerseJos Lommerse, Associate Director of Modeling Consulting Services, Certara. Jos Lommerse is a pharmacometrician with 15+ enthusiastic years using computation, math, and statistics to support pharmaceutical decision-making.  He was born amidst the colorful and fragrant flower fields of Holland. After completing studies in Chemical Engineering, he earned a PhD studying the structure of oligosaccharide chains from glycoproteins. After 6 years spent conducting research in Cambridge, UK, he joined Organon in 2000, initially as a molecular modeler and cheminformatician, later as a PK/PD M&S scientist. In 2014, he joined Quantitative Solutions which is now part of Certara. Jos is an Associate Director of Modeling Consulting services. He develops pop PK/PD models and conducts model-based meta-analyses to support a wide variety of drug development questions. Jos is especially interested in pediatrics and metabolic diseases.

Mother-to-child HIV transmission (MTCT) is a public health issue in low-resource countries. Prophylactic treatment of newborns shortly after birth is critical to prevent MTCT. Raltegravir is an antiretroviral agent which blocks a critical step in the virus lifecycle―integration of viral DNA into the host cell. Currently, this drug is only approved for treating infants at least 4 weeks old.

In this webinar, we discussed a population pharmacokinetic modeling and simulation approach to design a raltegravir dosing regimen for the prevention or treatment of HIV in newborns up to 6 weeks of age.