Applying MAM/PBPK Modeling to Predict Positive/Negative Food Effects: Approaches and Special Considerations
October 19 | Orlando, FL | 8:00 AM – 12:00 PM
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This workshop is FREE for all attendees. Seating limited, register soon!
Optimization of Exposure, Safety, and Efficacy through Modeling and Simulation: a Simulations Plus workshop on machine learning + PBPK (GastroPlus®), PKPD modeling (KIWI™), QSP (NAFLDsym®), and QST (DILIsym®)
October 20 | Orlando, FL | 8:30 AM – 4:00 PM
Modeling and simulation (M&S) is now a critical activity within the drug development process. The Simulations Plus family of companies has a wide range of experience and tools available to enable effective M&S. This workshop will provide a background knowledge of multiple M&S approaches and describe how Simulations Plus has partnered with developers to help facilitate better decisions and smarter investments. This workshop will provide an excellent foundation for those looking to learn more about various types of M&S approaches, as well as those looking for implementable solutions.
Session 1: Pharmacometric M&S Applications to Support Regulatory Approval – Development and Evolution of Population PK/PD Models using KIWI
The development and use of population-based PK/PD models across the drug development lifecycle will be described in this session, illustrating specific applications of population models to address critical development and regulatory review milestones. Examples will be presented in KIWI™ illustrating the use of population-based models during clinical development to describe and quantify variability in PK and PD, as well as to understand differences between healthy subjects and patients and the potential impact of intrinsic and extrinsic factors on PK/PD. Model-based clinical trial simulation strategies will also be demonstrated, illustrating assessment of the probability of success for particular trial designs, allowing for more efficient and cost-effective development programs. Population PK/PD models that describe exposure-response relationships, along with information regarding the key determinants of safety and efficacy, help to provide evidence of effectiveness to support approval decisions and importantly, to inform dose selection and justification as well as address the need for special population and individualized dosing recommendations in product labelling. Access to and facility with specialized M&S software tools is required to perform these assessments; KIWI™ provides a cloud-based communication and collaboration platform to use such tools, evaluate results, document, store, and share findings with teams of collaborators.
Session 2: Mechanistic PBPK modeling of special population groups – considerations and opportunities
Mechanistic modeling of special population groups continues to be a key component of GastroPlus®, with numerous companies applying the results to understand drug exposure differences, inform dose selection decisions, and support regulatory interactions. The focus of this session will be to discuss how physiological differences between ethnicities, pediatric groups, and disease states have been incorporated into mechanistic absorption (MAM)/physiologically based pharmacokinetic (PBPK) models to predict local and systemic exposure. A combination of presentations and examples using the GastroPlus® PBPK modeling platform will illustrate how to parameterize baseline models using early clinical data and, once validated, how they can be applied to other populations. Gaps in the current methods and future opportunities will also be explored.
Session 3: Applying QSP To the Liver - NAFLDsym for Predicting Efficacy of NAFLD/NASH treatment
This session will cover the basic theories and applications of quantitative systems pharmacology (QSP) software with a special emphasis on NAFLD/NASH treatment (NAFLDsym®). Interactive examples using NAFLDsym will illustrate typical data inputs utilized and address how to run simulations of expected outcomes and analyze results for impacting decisions. Attendees will understand the following important aspects of NAFLD/NASH modeling: key components of NASH pathophysiology, including steatosis, fibrosis, and inflammation; examples of targets represented for in silico evaluation; and stratification of simulated populations to address a planned or possible clinical study.
Session 4: Applying QST To the Liver - DILIsym for Predicting Drug-Induced Liver Injury
This closing session will cover the subject of quantitative systems toxicology (QST) for improved safety predictions, with an emphasis on the prediction of the potential for drugs and candidates to cause drug-induced liver injury (DILI) with DILIsym®. DILIsym examples will illustrate typical data inputs utilized and address how to run simulations of expected outcomes and analyze results for impacting decisions. Attendees will understand the following aspects of liver safety investigation: primary mechanisms often involved in DILI events, including mitochondrial dysfunction, oxidative stress production, lipotoxicity and bile acid transporter inhibition; in vitro assay design; general concepts accepted by regulators related to DILI monitoring and detection. Attendees will gain basic experience with translating in vitro data into DILIsym parameters, simulating expected DILI outcomes utilizing simulated populations (SimPops®), and using GastroPlus PBPK outputs to drive simulations.
Materials provided by sponsor:
All presentation files will be available in electronic format. Software will be demonstrated as part of the course. Software licenses are not required to attend the course.
Requirements from attendees:
All attendees will be responsible for registering in advance. Breakfast and lunch will be provided.
Hilton Orlando, 6001 Destination Pkwy, Orlando, FL 32819
Numbers 2 & 3!