Pavan K. Vaddady

Exposure-Overall Survival Analysis for Quizartinib in Newly Diagnosed Patients with FLT3-Internal-Tandem-Duplication-Positive Acute Myeloid Leukemia

Giovanni Smania, Anaïs Glatard, Pavan K. Vaddady, Shintaro Nakayama et autres

Objectives: Quizartinib, a highly potent type II FMS-like receptor tyrosine kinase 3 (FLT3) inhibitor, was evaluated in newly diagnosed FLT3-ITD-positive acute myeloid leukemia (AML) patients in the phase 3 QuANTUM-First trial [ 1]. It was administered in combination with standard induction and …

Quantitative Medicine: A Journal of Our Society, by Our Community, for Advancing Global Health

Pavan K. Vaddady, Rajanikanth Madabushi

Integrated Two-Analyte Population Pharmacokinetics Model of Patritumab Deruxtecan (HER3-DXd) Monotherapy in Patients with Solid Tumors

Yuan Xu, Mark Andrew Lee, Rujuta H. Joshi, Xiaoning Wang et autres

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Exposure–Response Relationships in Patients with Non‐Small‐Cell Lung Cancer and Other Solid Tumors Treated with Patritumab Deruxtecan (HER3‐DXd)

Li Li, Mark Andrew Lee, Rujuta H. Joshi, Yuan Xu et autres

Patritumab deruxtecan (HER3-DXd, also known as MK-1022), an antibody-drug conjugate consisting of a human epidermal growth factor receptor 3 (HER3) antibody attached to a topoisomerase I inhibitor payload (DXd), has demonstrated efficacy in patients with metastatic breast cancer and non-small cell lung …

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Population pharmacokinetic analysis of quizartinib in patients with newly diagnosed FLT3 ‐internal‐tandem‐duplication‐positive acute myeloid leukemia

Pavan K. Vaddady, Anaïs Glatard, Giovanni Smania, Shintaro Nakayama et autres

Abstract The population pharmacokinetics (PK) of quizartinib and its pharmacologically active metabolite AC886 have been previously described in healthy volunteers (HV) and relapsed/refractory (R/R) FLT3‐internal‐tandem‐duplication‐positive (FLT3‐IDT‐positive) acute myeloid leukemia (AML) patients receiving quizartinib monotherapy. In this analysis, we characterized the population PK …

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Concentration‐ QTcF analysis of quizartinib in patients with newly diagnosed FLT3 ‐internal‐tandem‐duplication‐positive acute myeloid leukemia

Pavan K. Vaddady, Giovanni Smania, Shintaro Nakayama, Hiroyuki Inoue et autres

Abstract Quizartinib prolongs QT interval through inhibition of the slow delayed rectifier potassium current (IKs). We used non‐linear mixed‐effects modeling to explore the relationship between quizartinib and its pharmacologically active metabolite AC886 and the Fridericia‐corrected QT interval (QTcF) in newly diagnosed acute …

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Within‐chain parallelization—Giving Stan Jet Fuel for population modeling in pharmacometrics

Casey Davis, Pavan K. Vaddady

Stan is a powerful probabilistic programming language designed mainly for Bayesian data analysis. Torsten is a collection of Stan functions that handles the events (e.g., dosing events) and solves the ODE systems that are frequently present in pharmacometric models. To perform a …

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Dose Optimization in Oncology Drug Development: An International Consortium for Innovation and Quality in Pharmaceutical Development White Paper

Divya Samineni, Karthik Venkatakrishnan, Ahmed A. Othman, Yazdi K. Pithavala et autres

The landscape of oncology drug development has witnessed remarkable advancements over the last few decades, significantly improving clinical outcomes and quality of life for patients with cancer. Project Optimus, introduced by the U.S. Food and Drug Administration, stands as a groundbreaking endeavor …

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Application of the model‐informed drug development paradigm to datopotamab deruxtecan dose selection for late‐stage development

Yasong Lu, Shuang Liang, Ying Sen Hong, Naoyuki Tajima et autres

To replace the conventional maximum tolerated dose (MTD) approach, a paradigm for dose optimization and dose selection that relies on model-informed drug development (MIDD) approaches has been proposed in oncology. Here, we report our application of an MIDD approach during phase I …

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Artificial Intelligence for Quantitative Modeling in Drug Discovery and Development: An Innovation and Quality Consortium Perspective on Use Cases and Best Practices

Nadia Terranova, Didier Renard, Mohamed H. Shahin, Sujatha S. Menon et autres

Recent breakthroughs in artificial intelligence (AI) and machine learning (ML) have ushered in a new era of possibilities across various scientific domains. One area where these advancements hold significant promise is model-informed drug discovery and development (MID3). To foster a wider adoption …

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Pharmacokinetics, Safety, and Tolerability of Imipenem/Cilastatin/Relebactam in Children with Confirmed or Suspected Gram‐Negative Bacterial Infections: A Phase 1b, Open‐Label, Single‐Dose Clinical Trial

John S. Bradley, Nataliia I. Makieieva, Camilla Tøndel, Emmanuel Roilides et autres

Abstract Imipenem/cilastatin/relebactam is approved for the treatment of serious gram‐negative bacterial infections in adults. This study assessed the pharmacokinetics (PK), safety, and tolerability of a single dose of imipenem/cilastatin/relebactam (with a fixed 2:1 ratio of imipenem/cilastatin to relebactam, and with a maximum …

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A Randomized, Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Novel Insulin Dimer

Geoffrey A Walford, Kelly Duncan, Moises Hernandez, Pavan K. Vaddady et autres

Insulin molecules of size much greater than natural insulin have been synthesized and studied with the intention of widening the therapeutic window between adequate glycemic control and hypoglycemia as compared with conventional insulins. MK-1092 is a synthetic insulin dimer with favorable properties …

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