PAGE 2024

Once again, a large, diverse, and expert team will represent Certara this year. Stop by our booth to say hello, share work, and discover new opportunities for partnership.

Karen Rowland Yeo, PhD | Piet van der Graaf, PharmD, PhD | Rik de Greef, MSc | Mirjam Trame, PharmD, PhD | Masoud Jamei, PhD | Mark Sale, MD | Keith Nieforth, PharmD | and more than 20 other scientists

Certara is proud to return with this annual tradition. Players of any skill level are encouraged to participate, and spectators are also welcome for the evening fun.

This will be an open, office-hours type session to introduce students to PMX analyses in R using Certara’s R speaks NLME, Pirana, and Pirana Darwin. Hands on access will be available, with experienced users available for demonstration and questions. Students are encouraged to bring their own problem sets for 1:1 instructor training. No previous training is required, instructors will also be available to demo toolsets, and assist users with how to get started with these recently introduced, innovative toolsets.

Would you like to modify and tailor population PBPK models? This course will review the principles of PBPK modelling, using the Simcyp Simulator and how to use Simcyp Designer to modify existing PBPK models with your own extension and link them to custom-built PD/QSP models. We will have lectures to introduce the PBPK models to be changed and have hands-on exercises to train the customisation of PBPK models with the Designer. No prior knowledge is required. Access to the Simcyp Simulator and Simcyp Designer will be provided. Participant are required to bring their own laptops as the workshop is hands-on intensive.

Key aspects of the course:

• Overview of PBPK modelling, using the Simcyp Simulator.
• Rapidly create new models in a graphical editor – the Simcyp Designer.
• Replace PBPK model components in Simcyp with a user-defined model.
• Adding components/modules to simcyp PBPK models.
• Extending PBPK models for large molecules.
• Building PBPK driven PD/QSP models.
• Incorporate population variability into the customized models.

COST £200+VAT Students (Coupon Code: STUDENT24) / £400+VAT Industry

Pharmacometrics in Late-Stage Development and Regulatory Submissions

Pharmacokinetic/Pharmacodynamic framework to support the subcutaneous dosing regimen of nemolizumab in subjects with moderate-to-severe atopic dermatitis
Floris Fauchet (1), Antonio Goncalves (1), Wannee Kantasiripitak (1), Eline van Maanen (1), Anna Largajolli (1), Vincent Duval (1), Liliana Ulianov (2), Michael Graeber (3), Patricia Fleuranceau Morel (3), Christophe Piketty (4), Luca Loprete (4), Nathalie Wagner (2)

Pharmacokinetic/Pharmacodynamic framework to support the subcutaneous dosing regimen of nemolizumab in subjects with Prurigo Nodularis
Floris Fauchet, (1), Wannee Kantasiripitak (1), Petra Jauslin (1), Vincent Duval (1), Antonio Goncalves (1), Anna Largajolli (1), Zarif Jabbar Lopez (2), Michael Graeber (3), Christophe Piketty (4), Patricia Fleuranceau Morel (3), Luca Loprete (4), Nathalie Wagner (3).

Pharmacokinetics/pharmacodynamics and exposure-response modelling of VH3810109 (N6LS) in antiretroviral therapy-naïve adults with HIV-1 from the Phase IIa BANNER Study
Yin Edwards (1*), Waqar Ashraf (1*), Thijs Zweers (1), Kathryn Brown (1), Jan Losos (2), Peter Leone (2), Margaret Gartland (2), Paul Wannamaker (2), Yash Gandhi (3)

Population Pharmacokinetic and Exposure Response Analysis of Belzutifan in Advanced Renal Cell Carcinoma
Anne Chain, Stefanie Hennig, Gerly van der Vleuten, Katrina Hui, Huub Jan Kleijn, Petra Jauslin

Pediatrics

Population pharmacokinetic modeling to support dose selection of zavegepant nasal spray in pediatrics
Craig M Comisar (1), Jim Hughes (2), Jose Francis (1), Gary Mo (2), Beikang Ge (3), Rajinder Bhardwaj (1), Mohamed H. Shahin (2), Jing Liu (2)

Optimizing Oncology Early-Stage Development

Comparison of tumor dynamics models and tumor growth inhibition metrics in support of decisions in early Phase Ib/II clinical oncology studies
Mathilde Marchand (1), Antonio Gonçalves (1), Francois Mercier (2), Pascal Chanu (3), Jin Y Jin (4), René Bruno (5)

Operating characteristics of TGI metrics to support early Phase Ib decisions in unresectable hepatocellular carcinoma patients based on an historical Phase III study (IMbrave150)
Antonio Gonçalves (1), Mathilde Marchand (1), Victor Poon (2), Phyllis Chan (2), René Bruno (3)

Model Based Meta Analysis

Understanding onset and response of two key endpoints in Systemic Lupus Erythematosus
Anna Largajolli,1 Raj Thatavarti,1 Matthew L. Zierhut,1 Garrett Nieddu,2 Tjerk JH Bueters,2 Nancy Kim,2 Martin Johnson3

Clinical Model-Based Meta-Analysis applied to Vaccine Development for SARS-CoV-2 Variants
Anna Largajolli (1), Akshita Chawla (2), Bhargava Kandala (2), Soumya Perinparajah (1), Nele Plock (1), Kenny Watson (1), Niharika Gandhapuneti (1), Raj Thatavarti (1), S. Y. Amy Cheung (1), Rik de Greef (1), Jeffrey R. Sachs (2)

Comparative assessment of incretin therapies on weight loss through a model-based meta-analysis approach
Akshita Chawla, Peter Chang, Li Qin, Matthew L. Zierhut, Maria Trujillo

Impact of censoring on non-linear effect modeling of aggregate-level survival data
Renwei Zhang (1), Tingjie Guo (1), Li Qin (2), Rik de Greef (2), Matthew L. Zierhut (2), Laura B. Zwep (1), J. G. Coen van Hasselt (1)

Methodology
mlcov: New Machine Learning Based R package for Covariate Selection
Ibtissem Rebai, Vincent Duval, Ayman Akil, James Craig, Mike Talley, Anna Largajolli, and Floris Fauchet

Mastering upset plots: a comprehensive tutorial for effective data visualization in pharmacometrics and drug development
Mahmoud A. Aafifi (1), Samer Mouksassi (1)

The Applied Pharmacometrics Training Program – Year 3 Sustainability
Innocent Gerald Asiimwe1,2, Samer Mouksassi3, Rik de Greef4, Eric Decloedt5, Paolo Denti2,6, Phumla Sinxadi2,6, Catriona Waitt1,2,7, Goonaseelan (Colin) Pillai2,6,8

nlmixr2, rxode2 and Monolix: interchangeable models using monolix2rx and babelmixr2
Matthew Fidler (1, 9), William S. Denney (2, 9), John Harrold (8, 9), Richard Hooijmakers (4, 9), Rik Schoemaker (3, 9), Max Taubert(1, 9), Mirjam Trame (5, 9), Theodoros Papathanasiou (6, 9), Justin Wilkins (3, 9)

FOCE generalized log-likelihood using nlmixr2
Matthew Fidler (1, 7), William S. Denney (2, 7), John Harrold (7), Richard Hooijmakers (4, 7), Max Taubert (1, 7), Mirjam N. Trame (5, 7), Theodoros Papathanasiou (6, 7), Rik Schoemaker (3, 7), Justin Wilkins (3, 7)

The drug titration paradox in the presence of intra-individual variation: can we estimate the true concentration-effect relationship?
Sebastiaan C. Goulooze (1), Elke H.J. Krekels (2,3) Martijn van Noort (1), Catherijne A.J. Knibbe (3,4)

The International Society of Pharmacometrics’ Special Interest Group on Quantitative Systems Pharmacology (ISoP QSP SIG): Recent Developments and Future Vision
Cesar Pichardo-Almarza (1), Krina Mehta (2), Anna Kondic (3), Yannis Androulakis (4), Marissa Renardy (5), Lourdes Cucurull-Sanchez (6)

Beyond the Liver; In Silico Screening for Tissue-Specific Oligonucleotide Delivery Receptors
Abdallah Derbalah (1), Felix Stader (1), Cong Liu (1), Adriana Zyla (1), Armin Sepp (1)

Performance of Machine Learning Algorithms for Model Selection
Xinnong Li (1), Mark Sale (2), Keith Nieforth (2), James Craig (2), Fenggong Wang (3), David Solit (4), Kairui Feng (3), Meng Hu (3), Robert Bies(1), Liang Zhao (3)

Drug/Disease Modelling

The impact of drug properties and severity of obesity on renal clearance through glomerular filtration and active tubular secretion
Tan Zhang (1), Elisa A.M. Calvier (2), Elke H.J. Krekels (1,3)*, Catherijne A.J. Knibbe (1,4)*

Physiologically Based Pharmacokinetic modelling of the Drug-Drug Interaction between Ivacaftor and Lefamulin in Cystic Fibrosis patients
Wolfgang W. Wicha1, Magali Amiel2, Alice Ke2, Hannah Jones2, Steven P. Gelone3

Time-dependent pharmacokinetics of hydromethylthionine mesylate (HMTM), a tau aggregation inhibitor, in healthy volunteers and patients with Alzheimer’s Disease
Eline van Maanen (1), Antonio Goncalves (1), Lu Chen (1), Floris Fauchet (1), Sinziana Cristea (1), James Smith (1), Tom Baddeley (2,3), Fiona Hewitt (2), Bjoern Schelter (2,3), Claude Wischik (2,3)

Quantifying the sensitivity and specificity of CYP450 probe drugs in predicting in vivo enzyme activity under (patho)physiological conditions
A. M. (Marinda) van de Kreeke (1)*, Laura M. de Jong (1)*, Mariam Ahmadi (1), Jesse J. Swen (2), Catherijne A.J. Knibbe (1,3), J.G. Coen van Hasselt (1), Martijn L. Manson (1), Elke H.J. Krekels (1,4) *both authors contributed equally

Physiologically based pharmacokinetic modelling to predict the concentration-time profile of an antibody-drug conjugate and hepatic and renal impairment.
Felix Stader, Cong Liu, Adriana Zyla, Abdallah Derbalah, Armin Sepp

Pharmacometric modelling to describe pharmacokinetics and exposure-response of ivermectin in adolescent patients infected with Trichuris trichiura
David Ajayi (1,2), Ochuko M. Orherhe (1,3), Goonaseelan (Colin) Pillai (1,4,5), Samer Mouksassi (1,6), Britta Steffens (7), Dominic Bräm (7), Viviane Sprecher (8,9), Daniela Hoffmann (8,9), Michael Buettcher (7,9,10), Jean T. Coulibaly (11,12), Said M. Ali (13), Jennifer Keiser (8,9), Marc Pfister (7,11)

Population PK and exposure-response modeling to support the design of trials with Debio 0123, a WEE1 inhibitor, in cancer patients
Vito Dozio (1), Philippe B. Pierrillas (2), Kyriakos P. Papadopoulos (3), Hans Gelderblom (4), Sandrine Micallef (1), Camille Riff (1), Hashim Michla (1), Tri Tat (1), Marie-Claude Roubaudi-Fraschini (1), Noemie Luong (1), Mokhtar Omar (1), Rikke Frederiksen Franzen (1), Melanie Wirth (1), Caroline Mathon (1), Victor Rodriguez Freixinos (1), Esteban Rodrigo Imedio (1), Anne Bellon (1)

A PBPK model of 4β-hydroxycholesterol, an endogenous biomarker for hepatic CYP3A activity.
Aneesh Karkhanis (1), Matthew Harwood (1), Frederic Bois (1), Sibylle Neuhoff (1)

External Validation of a Population Pharmacokinetic Model for Morphine and its Metabolites in Children under 3 Years who Underwent Cardiothoracic Surgery
Maria Xiberras (1,2), Gerdien Zeilmaker-Roest (2), Swantje Völler (1), Elke H.J. Krekels (1,3), A.J. (Bram) Valkenburg (4), Dick Tibboel (2), Enno Wildschut (2), Catherijne A.J. Knibbe (1,5)

Assessing the impact of choosing different estimated glomerular filtration rate (eGFR) equations on pharmacokinetic models: A proof-of-concept study with illustrative examples
(1, 2) Thao-Nguyen Pham, (2) Yu-Wei Lin, (2) S. Y. Amy Cheung

Natural disease progression model with transition probabilities to describes the continuum of Alzheimer’s disease
Noel Patson1,2*, Marwa E.Elhefnawy 2,3*, Samer Mouksassi 4, Goonaseelan (Colin) Pillai 2,5, Emmanuel Chigutsa 6, Ivelina Gueorguieva 7

Same Dissolution Profile – Different Virtual Bioequivalence (VBE) Outcome! Input-Dependent Propagation of Between Subject Variability (BSV) in Gut Physiology to Dissolution and VBES
Masoud Jamei, SVP R & D, David Turner, Amin Rostami-Hodjegan

Population PK and PKPD modeling of TBA-7371 in Healthy Adults and Adults with tuberculosis
Shayne Watson (1), Micha Levi (1), David Holtzman (1), David Salinger (2), Kelly Stinson (1), Aparna Anderson (1), Elizabeth Grekas (1), Charles Wells (1)

The impact of being born Small for Gestational Age (SGA) on the clearance of vancomycin versus morphine and midazolam
Anne van Rongen (1), Madelein E. Nuis (1), Runyi Ma (1), Karel Allegaert (2,3,4), Swantje Völler (1), Anne Smits (3,6), Robert B. Flint (4,7), Saskia N. de Wildt (7,8), Dick Tibboel (9), Sinno H.P. Simons (7), Elke H.J. Krekels (1,5), Catherijne A.J. Knibbe (1,7,10)

Relative impact of CYP2D6 phenotype, physiological changes and hepatic extraction ratio on drug exposure during pregnancy
Karen Rowland Yeo

Clinical Applications

Successful validation of a model-informed precision dosing instrument for meropenem in critically ill patients, the DoseCalculator, against NONMEM®
Franz Eric Weber (1,2), Ferdinand Anton Weinelt (1,2), Christin Nyhoegen (1), Frieder Pfäfflin (3), Anja Theloe (4), Ulrike Trost (3), Peggy Kießling (5), Wilhelm Huisinga (6), Sebastian Georg Wicha (7), Robin Michelet (1), Stefanie Hennig (1,8,9), Miriam Songa Stegemann (3), Charlotte Kloft (1)

Real-World Data (RWD) in Pharmacometrics

Real World Data – Realistic Population — Evidence for Unrecognized Pharmacokinetics of Renally Eliminated Drugs
Nick Holford (1), Conor J O’Hanlon (1), Karel Allegaert (2), Brian Anderson (3), Amilcar Falcão (4), Nicolas Simon (5), Yoke-Lin Lo (6), Alison H Thomson (7), Catherine M Sherwin (8), Evelyne Jacqz-Aigrain (9), Carolina Llanos-Paez (10), Stefanie Hennig (11) , Linas Mockus (12), Carl Kirkpatrick (13)

RDarwin: An R package for Machine Learning using pyDarwin and Certara’s pharmacometrics modeling language (PML) and NLME engine
Keith Nieforth (1), Mark Sale (1), James Craig (1), Michael Tomashevskiy(1)