Lead Investigator: Mary Ann Lukas, GlaxoSmithKline
Title of Proposal Research: Modeling and Simulation of ambrisentan pharmacokinetics in young children
Vivli Data Request: 7396
Funding Source: None
Potential Conflicts of Interest: Employee of GSK
Summary of the Proposed Research:
The data being requested will be incorporated into a modelling and simulation analysis of ambrisentan in the paediatric population (aged 4 to less than 8 years). This is being done for inclusion in GSK’s regulatory submission to EMA, as development in this age group is a requirement; these data provide important support for GSK’s position on development approach. Given this purpose, there is no specific mitigation planned or in our view needed for the relationship stated.
The detailed PK data requested will allow a comparison between the observed PK data in the 4-<8years and the simulated PK profiles in the 4- <8year group using the integrated population PK model in adult and children 8 to <18 years derived by GlaxoSmithKline. This work is being done to enhance the design of the exposure extrapolation strategy to the 4 to less than 8 year old population and will potentially be submitted in regulatory submission to EMA as supportive data
Statistical Analysis Plan:
An integrated population pharmacokinetic (popPK) model has been developed for ambrisentan incorporating previous data from adult and 8 to less than 18 year old population. This model will be used to simulate the PK of ambrisentan based on the population demographic distribution in the (Hill, 2020) investigational study. Multiple simulations (eg 1000) will be performed per each individual in the (Hill, 202) dataset using the parameter estimates from the final integrated popPK model including the variability from inter-subject and residual errors.
Requested Studies:
Safety, Pharmacokinetics (PK) and Hemodynamic Effects of Ambrisentan in Single Ventricle Pediatric Patients
Data Contributor: Duke University School of Medicine/Duke University Hospital
Study ID: NCT02080637
Sponsor ID: Pro00050118
Summary of Results:
Data Request title: Modeling and Simulation of ambrisentan pharmacokinetics in young children