Appraisal of ICH E14/S7B Q&As adopted in February 2022 using thorough QT/QTc study data for a4-integrin antagonist carotegrast methyl in Japanese healthy subjects

Article Gastroenterology & Hepatology

AJM300 (carotegrast methyl), an oral antagonist of α4-integrin, as induction therapy for patients with moderately active ulcerative colitis: a multicentre, randomised, double-blind, placebo-controlled, phase 3 study

Katsuyoshi Matsuoka et al.

Summary: This study evaluated the efficacy and safety of oral small-molecule drug AJM300 in patients with moderately active ulcerative colitis, showing that AJM300 could be a novel induction therapy for this condition.

LANCET GASTROENTEROLOGY & HEPATOLOGY (2022)

添加到收藏夹

Article Cardiac & Cardiovascular Systems

Cardiohemodynamic and Arrhythmogenic Effects of the Anti-Atrial Fibrillatory Compound Vanoxerine in Halothane-Anesthetized Dogs

Mihoko Hagiwara-Nagasawa et al.

Summary: Vanoxerine shows inhibitory effects on ionic currents and has potential in treating atrial fibrillation; however, high doses may lead to adverse effects such as prolonged repolarization and increased atrial refractoriness. These findings suggest that vanoxerine may not be an ideal anti-atrial fibrillatory drug due to its potential for triggering torsade de pointes.

CARDIOVASCULAR TOXICOLOGY (2021)

添加到收藏夹

Review Pharmacology & Pharmacy

Time for a Fully Integrated Nonclinical-Clinical Risk Assessment to Streamline QT Prolongation Liability Determinations: A Pharma Industry Perspective

Hugo M. Vargas et al.

Summary: Efficient assessment of drug-induced QTc prolongation remains a concern of drug developers and regulators worldwide. While successful, nonclinical evaluations currently have minimal impact on clinical QTc prolongation assessment. Fully integrating nonclinical and clinical data can simplify drug development processes.

CLINICAL PHARMACOLOGY & THERAPEUTICS (2021)

添加到收藏夹

Review Pharmacology & Pharmacy

Translational Models and Tools to Reduce Clinical Trials and Improve Regulatory Decision Making for QTc and Proarrhythmia Risk (ICH E14/S7B Updates)

David G. Strauss et al.

Summary: After certain drugs were withdrawn from the market due to the risk of drug-induced torsade de pointes (TdP), the ICH released guidelines focusing on the assessment of surrogate biomarkers for TdP in 2005. Vargas et al. proposed that double-negative nonclinical data may not require detailed clinical QTc evaluation due to low probability of QTc prolongation and TdP, leading to the ICH releasing a new Draft Guideline to address this. The ICH's new guidelines aim to reduce Thorough QT (TQT) studies using double-negative nonclinical data and achieving a low-risk determination in situations where TQT studies are not feasible.

CLINICAL PHARMACOLOGY & THERAPEUTICS (2021)

添加到收藏夹

Article Pharmacology & Pharmacy