A5028399560- Influenza Virus Research Studies
- Respiratory viral infections research
- Liver Disease Diagnosis and Treatment
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Carcinogens and Genotoxicity Assessment
- Computational Drug Discovery Methods
- Drug-Induced Hepatotoxicity and Protection
- Pharmacogenetics and Drug Metabolism
- Metabolomics and Mass Spectrometry Studies
- Alcohol Consumption and Health Effects
- Long-Term Effects of COVID-19
- Liver physiology and pathology
- SARS-CoV-2 detection and testing
- Chemotherapy-induced organ toxicity mitigation
- Viral Infections and Immunology Research
- Cancer-related Molecular Pathways
- MicroRNA in disease regulation
- Genomics, phytochemicals, and oxidative stress
- Renal and related cancers
- Drug Transport and Resistance Mechanisms
- interferon and immune responses
- Gene expression and cancer classification
- Chronic Kidney Disease and Diabetes
- Acute Kidney Injury Research
Shionogi (Japan)
2015-2025
University Hospital Kyoto Prefectural University of Medicine
2025
Futaba (Japan)
2007-2023
Osaka Prefecture University
2012-2019
University of North Carolina at Chapel Hill
2010-2016
Texas A&M University
2015
National Institute of Biomedical Innovation, Health and Nutrition
2006-2014
Hankyu Hanshin Holdings (Japan)
2014
Ehime University
2008
Tokyo University of Agriculture and Technology
2002
Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease. It has shown therapeutic activity in preclinical models A and B virus infections, including strains resistant to current antiviral agents.We conducted two randomized, double-blind, controlled trials involving otherwise healthy outpatients with acute uncomplicated influenza. After dose-ranging (10 40 mg) placebo-controlled trial, we undertook placebo- oseltamivir-controlled trial single, weight-based doses...
Abstract Baloxavir acid (BXA), derived from the prodrug baloxavir marboxil (BXM), potently and selectively inhibits cap-dependent endonuclease within polymerase PA subunit of influenza A B viruses. In clinical trials, single doses BXM profoundly decrease viral titers as well alleviating symptoms. Here, we characterize impact on BXA susceptibility replicative capacity variant viruses detected in post-treatment monitoring studies. We find that I38T substitution is a major pathway for reduced...
Single-dose baloxavir rapidly reduces influenza virus titers and symptoms in patients with uncomplicated influenza, but viruses reduced vitro susceptibility due to amino acid substitutions at position 38 of polymerase acidic protein (PA/I38X) sometimes emerge.We evaluated the kinetics, risk factors, effects on clinical virologic outcomes emergence PA/I38X-substituted viruses.Viruses containing PA/I38X were identified 3-9 days after treatment 9.7% (36/370) patients, whom 85.3% had transient...
This phase 2b part of a randomized 2/3 study assessed the efficacy and safety ensitrelvir for mild-to-moderate coronavirus disease 2019 (COVID-19) during Omicron epidemic.Patients were (1:1:1) to orally receive fumaric acid 125 mg (375 on day 1) or 250 (750 placebo once daily 5 days. The co-primary endpoints change from baseline in severe acute respiratory syndrome 2 (SARS-CoV-2) titer 4 time-weighted average up 120 hours total score predefined 12 COVID-19 symptoms. Safety was through...
This multicenter, double-blind, phase 2a part of a 2/3 study assessed the efficacy and safety ensitrelvir, novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3C-like protease inhibitor, in Japanese patients with mild-to-moderate disease 2019 (COVID-19) or asymptomatic SARS-CoV-2 infection. Sixty-nine were randomized (1:1:1) to orally receive 5-day ensitrelvir fumaric acid (375 mg on day 1 followed by 125 daily, 750 250 daily) placebo up until 28.
Importance Treatment options for COVID-19 are warranted irrespective of the presence risk factors severe disease. Objective To assess efficacy and safety ensitrelvir in patients with mild to moderate COVID-19. Design, Setting, Participants This phase 3 part a 2/3, double-blind, placebo-controlled randomized clinical trial was conducted from February 10 July 10, 2022, 28-day follow-up period, at 92 institutions Japan, Vietnam, South Korea. Patients (aged 12 <70 years) within 120...
Quantitative structure-activity relationship (QSAR) modeling and toxicogenomics are typically used independently as predictive tools in toxicology. In this study, we evaluated the power of several statistical models for predicting drug hepatotoxicity rats using different descriptors molecules, namely, their chemical profiles. The records were taken from Toxicogenomics Project rat liver microarray database containing information on 127 drugs ( http://toxico.nibio.go.jp/datalist.html ). model...
Human hepatocellular carcinoma (HCC) develops most often as a complication of fibrosis or cirrhosis. While human studies HCC provide crucial insights into the molecular signatures HCC, seldom do they address etiology HCC. Mouse models are essential tools for investigating pathogenesis HCC; however, overwhelming majority cancer in rodents not feature liver fibrosis. Detailed this unit is protocol an experimental mouse model that arises association with advanced The disease induced by single...
Baloxavir marboxil (baloxavir) is a polymerase acidic protein (PA) endonuclease inhibitor with clinical efficacy in the treatment of uncomplicated influenza, including outpatients at increased risk for complications. The postexposure prophylactic baloxavir household setting unclear.We conducted multicenter, double-blind, randomized, placebo-controlled trial to evaluate contacts index patients confirmed influenza during 2018-2019 season Japan. participants were assigned 1:1 ratio receive...
We assessed the safety and effectiveness of baloxavir marboxil administration in Japanese children with influenza.This open-label study administered 1 weight-adjusted dose to 107 aged 1-11 years laboratory-confirmed, febrile influenza virus infection ≤48 hours duration.Adverse events (AEs) were reported 34.6% patients, most commonly vomiting (7.5%); no serious AEs or causing discontinuation occurred. The median time alleviation illness was 44.6 (95% confidence interval, 38.9-62.5 hours),...
Limited treatment options exist for patients with mild-to-moderate coronavirus disease 2019 (COVID-19), irrespective of vaccination history or risk status. Ensitrelvir is a novel oral severe acute respiratory syndrome 2 (SARS-CoV-2) 3C-like (3CL) protease inhibitor. While phase studies ensitrelvir have demonstrated promising results in treating COVID-19, evaluation its clinical efficacy due to shifting status and emergence the Omicron variant represents significant challenges. Here, we...
This study aimed to evaluate the effectiveness of ensitrelvir, an oral antiviral, in reducing hospitalization risk outpatients at high-risk for severe COVID-19 during Omicron era. was a retrospective using large Japanese health insurance claims database. It included symptoms who received their first diagnosis between November 2022 and July 2023. The aged ≥ 18 years. primary endpoint all-cause 4-week period from date outpatient medication, comparing ensitrelvir group (n = 5177) no antiviral...
Ensitrelvir, a severe acute respiratory syndrome coronavirus-2 main protease inhibitor, has demonstrated clinical and virologic efficacy in previous studies. In this global phase 3 trial, nonhospitalized adults with mild-to-moderate coronavirus disease 2019 (COVID-19) symptom onset within 5 days were randomized (1:1) to receive once-daily ensitrelvir (375 mg day 1, 125 2-5) or blinded matching placebo. The primary endpoint was the restricted mean time sustained (≥2 days) resolution of 15...
Hepatocellular carcinoma (HCC) mostly develops in patients with advanced fibrosis; however, the mechanisms of interaction between a genotoxic insult and fibrogenesis are not well understood.This study tested hypothesis that fibrosis promotes HCC via mechanism involves activation liver stem cells.First, B6C3F1 mice were administered diethylnitrosamine (DEN; single ip injection 1 mg/kg at 14 days age).Second, carbon tetrachloride (CCl 4 ; 0.2 ml/kg, 2/week starting 8 weeks age) was for 9 or to...
ABSTRACT Cardiotoxicity is one of the major safety concerns in drug development. Therefore, detecting and monitoring cardiotoxicity throughout preclinical clinical studies important for pharmaceutical companies. The present study was conducted order to explore a plasma miRNA biomarker rats. As organ specificity an factor biomarker, we analyzed microarray dataset 55 organs/tissues normal male Based on this analysis, 5 miRNAs consisting miR‐208 (heart‐specific), miR‐1, miR‐133a, miR‐133b...
Abstract MicroRNAs (miRNAs) are small (~22 nucleotide) noncoding RNAs that play pivotal roles in regulation of gene expression. The value miRNAs as circulating biomarkers is now broadly recognized; such tissue-specific can be used to monitor tissue injury and several pathophysiological conditions organs. In addition, miRNA profiles normal organs tissues important for obtaining a better understanding the source modulated blood how those modulations reflect various physiological toxicological...
This exploratory analysis of the double-blind, phase 3, SCORPIO-SR trial assessed effect ensitrelvir in preventing post coronavirus disease 2019 (COVID-19) condition (PCC). Patients with mild-to-moderate COVID-19 were randomized (1:1:1) within 120 h symptom onset; received 5-day oral 125 mg (375 on day 1), 250 (750 or a matching placebo once daily; and for severity typical PCC symptoms using self-administered questionnaire. In total, 341, 317, 333 patients 125-mg, 250-mg, groups,...
Abstract Background Ensitrelvir is an oral SARS-CoV-2 3CL protease inhibitor developed to treat COVID-19. In the Phase3 SCORPIO-SR trial targeting mild/moderate COVID-19 patients, proportion of patients who experienced Post Condition (PCC) until Day 337 was lower in ensitrelvir groups than placebo group [A. Fukushi et al. The Ninth ESWI Influenza Conference]. Here we report effect on PCC less symptomatic enrolled another part, Phase2b/3. Proportion with Post-COVID-19 and risk reduction...