An interactive pharmacometric case study for an antibody exhibiting TMDD
In this 1.5-day course we will specifically discuss the importance of understanding the pharmacology of monoclonal antibodies (mAbs) to make the right decisions in target-mediated drug disposition (TMDD) model development. If you want to learn more on 1) the relevance of mechanistic modelling for mAbs, 2) the considerations with regards to scaling the model for first in human (FIH) approaches, and 3) what TMDD models are, what approximations may be applicable and how to use these models for (non-) clinical data.
In this LAP&P interactive course, we will mimic a real-life example of a mAb with straightforward target engagement. After a short introduction, we will directly dive into a hands-on session, in which the participants work in small groups on TMDD modelling challenges using a nlmixr2 within a shinyMixR workflow.
We will focus on both the technical challenges associated with applying these models, and on the right interpretation of the acquired results. In the morning of the first of the day, we will start with the analysis of a preclinical dataset, after which we will proceed to the design of a first in human trial (e.g., dose and sampling selection). During the afternoon and the day after we’ll work on the analysis of the resulting clinical data.
For whom?
This course is intended for pharmacometricians and pharmacokineticists with basic modelling experience. Participants will be introduced into the basic concepts and application of TMDD models through ‘learning by doing’. Some population PK/PD modelling experience is required. An installation in R is required and installation instructions will be shared shortly before the course. No experience is required with other specific software as we will guide you through the use of nlmixr2 within a shinyMixR workflow [Fidler et al., 2019, Hooijmaijers 2018]. Scripts and code will be available to efficiently work on the case and for more information on these opensource packages please visit: https://nlmixr2.org/.
Participants will be asked up front to provide some detail on their experience, such that we can suggest further reading in case needed.
Workshop tutors: Tamara van Steeg & Sven Hoefman
Date & Time:
Monday 2nd of June, 13:00 -17:00
Tuesday 3rd of June, 9:00 -17:00
Venue:
Thessaloniki, Hotel Capsis
Fees:
- Commercial/Industry: 800 (600**) EUR excl. VAT.
- Academia/PHD Students: 400 (300**) EUR excl. VAT.
**Early bird until 1st of April.
References
Mager & Jusko 2001 General pharmacokinetic model for drugs exhibiting target-mediated drug disposition. Journal of Pharmacokinetics and Pharmacodynamics 28 (6): 507-32.
Gibiansky et al., 2008 Approximations of the target-mediated drug disposition model and identifiability of model parameters. Journal of Pharmacokinetics and Pharmacodynamics 35 (5): 573-91.
Koch et al., 2016 Target-mediated drug disposition with drug–drug interaction, Part I: single drug case in alternative formulations. Journal of Pharmacokinetics and Pharmacodynamics 44 (1): 17–26.
Fidler et al., 2019 Nonlinear Mixed-Effects Model Development and Simulation Using nlmixr and Related R Open-Source Packages. CPT Pharmacometrics Systems Pharmacology 8(9): 621-633.
Hooijmaijers 2018 shinyMixR: A project-centric R/Shiny run management tool for nlmixr. Poster presented at PAGE, PowerPoint Presentation (page-meeting.org)