Background/Aims To assess the dose‐proportionality of single oral doses of a sustained‐release formulation of desvenlafaxine succinate (DVS‐SR) in healthy subjects. Methods A randomized single‐dose crossover study was conducted in 24 healthy male subjects. Three (3) doses (100, 300, and 600 mg) were given by using 100‐mg tablets after a medium‐fat breakfast. Routine laboratory tests, vital signs, and electrocardiograms (ECG) were measured throughout the study. Plasma concentrations of desvenlafaxine (DV) were analyzed by model‐independent methods and linear dose proportionality of Cmax and AUC were assessed by an exponential regression model. Results DV was slowly absorbed (mean tmax of 7 to 8 hours) with slow elimination (mean t1/2 of 11 hours). Cmax and AUC increased linearly over the dose range of 100 to 600 mg. The between‐subject variability was low with the percent coefficient of variations (%CV) under 25% for Cmax, t1/2, and AUC. Nausea and dizziness were the most common adverse events. No clinically relevant changes occurred in ECG intervals and laboratory tests. Conclusion Increases in the Cmax and AUC of DV were linear over the dose range studied (100, 300, and 600 mg). DVS‐SR was generally well tolerated at all doses. Clinical Pharmacology & Therapeutics (2005) 77, P82–P82; doi:
Background Respiratory syncytial virus (RSV) is a major cause of infant morbidity and mortality worldwide and could be preventable by vaccination in pregnancy. Methods We conducted a randomized, placebo-controlled phase 2b trial evaluating safety, immunogenicity, and potential efficacy of a bivalent RSV prefusion F vaccine (RSVpreF) in pregnant women and their infants. Participants were randomized between 24- and 36-weeks’ gestation to receive 120 or 240 µg RSVpreF, with or without aluminum hydroxide, or placebo. Results This final analysis includes 579 women and 572 infants in 4 countries (Argentina, Chile, South Africa, and the US); 462 (79.8%) women received RSVpreF. Postvaccination reactions, most commonly injection site pain, fatigue, and myalgia, were generally mild-to-moderate. Adverse events (AEs) in the month following vaccination (maternal) or birth (infant) were mostly anticipated events in pregnancy and the neonatal period, respectively, and were similar between vaccine and placebo groups. No AEs were considered related to vaccination. For all RSVpreF groups, 50% neutralizing titers for both RSV-A and RSV-B rose sharply by 2 weeks after vaccination. At delivery occurring a mean of ∼8 weeks later, geometric mean titer (GMT) ratios for combined RSV-A/B between vaccine and placebo recipients’ infants were 10.9 to 13.6. Transplacental transfer ratios (all groups) were 1.39 to 1.83. Infant GMTs were higher in infants whose mothers had received RSVpreF versus placebo through 6 months of life; the estimated half-life of infant combined 50% RSV-A/B neutralizing titers was 41 days. Infants of women immunized across the range of assessed gestational ages had similar cord blood titers and transplacental transfer ratios. Observed efficacy (95% CI) against medically attended and severe medically attended infant RSV lower respiratory tract illness (LRTI) through 180 days in an exploratory analysis was 84.7% (21.5%, 97.6%) and 91.5% (-5.6%, 99.8%), respectively. Conclusion RSVpreF was well-tolerated in pregnant women, elicited robust neutralizing responses with efficient transplacental transfer, and has the potential to prevent infant RSV LRTI. Disclosures Eric A. F. Simões, MD, M.B., B.S., DCH, Abbvie: DSMB|Astra Zeneca: Grant/Research Support|Bill and Melinda Gates Foundation: Grant/Research Support|Bill and Melinda Gates Foundation: DSMB|GSK Inc.: DSMB|Johnson and Johnson: Grant/Research Support|Merck Inc: Advisor/Consultant|Merck Inc: Grant/Research Support|Nivavax: Grant/Research Support|Pfizer Inc: Advisor/Consultant|Pfizer Inc: Grant/Research Support|Regeneron: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Shabir A. Madhi, MBBCh, FCPaeds, MMed, PhD, AstraZeneca: Funding to institution for conduct of study Kimberly J. Center, M.D., Pfizer: Employee|Pfizer: Stocks/Bonds Jose M. Novoa Pizarro, MD, AstraZeneca: Grant/Research Support|Medimmune: Grant/Research Support|MSD: Grant/Research Support|Pfizer: Grant/Research Support|Regeneron: Grant/Research Support Kena A. Swanson, Ph.D., Pfizer: employee of Pfizer David Radley, MS, Pfizer: Employee|Pfizer: Stocks/Bonds Stephanie B. McGrory, B.S.N., Pfizer: Employee|Pfizer: Stocks/Bonds Emily A. Gomme, Ph.D., Pfizer: Stocks/Bonds Daniel A. Scott, MD, Pfizer: Employee|Pfizer: Stocks/Bonds Kathrin U. Jansen, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds William C. Gruber, MD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Alejandra C. Gurtman, M.D., Pfizer: employee of Pfizer.
Pediatric central nervous system cancers are the leading disease-related cause of death in children and there is urgent need for curative therapeutic strategies for these tumors. To address the urgency, Children’s Brain Tumor Network (CBTN) has advanced an open science model to accelerate the research discovery for pediatric brain tumors. In first phase of Open Pediatric Brain Tumor Atlas (OpenPBTA) effort CBTN together with Pacific Pediatric Neuro-Oncology Consortium (PNOC) and Gabriella Miller Kids First Data Resource Center (KFDRC) created and characterized over 1000 clinically annotated pediatric brain tumors. The second phase of the OpenPBTA, through resource awards and collaboration across KFDRC, the NCI Childhood Cancer Data Initiative (CCDI), Clinical Proteomic Tumor Analysis Consortium (CPTAC), Center for Cancer Research and partnered institutions and foundations has expanded molecular characterization for an additional 1900 pediatric brain tumor patients and their families. This includes the processing and characterization of >8000 specimens across >50 brain tumor diagnoses. This expansion builds off multimodal data including whole genome, RNA, miRNA and methylation sequencing, proteomics, lipidomics and/or metabolomics. Molecular data is linked to longitudinal clinical data, imaging data, histology images, and pathology reports. The data deposition in the cloud-based environment of the NCI’s CCDI and KFDRC to provide near real-time integration, dissemination, processing, and sharing capability. The approach leverages the DRC platform’s cloud-based computational environment through CAVATICA portal shareable pipelines. Data can be explored via PedcBioPortal, a data visualization/analysis application integrating additional public and deposited datasets. This OpenPBTA expansion released with no embargo provides one of the largest deeply characterized cohorts of samples and associated clinical data for >3000 pediatric brain tumor patients. CBTN’s open-science, rapid-release model aims to accelerate pediatric biomarker and drug discovery research and supports clinical trial development on behalf of changing the outcome for kids with brain tumors.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.