GSK2374697, a Novel Albumin-Binding Domain Antibody (AlbudAb), Extends Systemic Exposure of Exendin-4: First Study in Humans—PK/PD and Safety
2014; Wiley; Volume: 96; Issue: 6 Linguagem: Inglês
10.1038/clpt.2014.187
ISSN1532-6535
AutoresR. O’Connor‐Semmes, Jian Lin, Rebecca J. Hodge, Susan Andrews, Jack P. Chism, Arpita Choudhury, Derek J. Nunez,
Tópico(s)Pharmaceutical studies and practices
ResumoClinical Pharmacology & TherapeuticsVolume 96, Issue 6 p. 704-712 Articles GSK2374697, a Novel Albumin-Binding Domain Antibody (AlbudAb), Extends Systemic Exposure of Exendin-4: First Study in Humans—PK/PD and Safety R L O'Connor-Semmes, Corresponding Author R L O'Connor-Semmes [email protected] GlaxoSmithKline, R&D, Research Triangle Park, North Carolina, USASearch for more papers by this authorJ Lin, J Lin GlaxoSmithKline, R&D, Research Triangle Park, North Carolina, USASearch for more papers by this authorR J Hodge, R J Hodge GlaxoSmithKline, R&D, Research Triangle Park, North Carolina, USASearch for more papers by this authorS Andrews, S Andrews GlaxoSmithKline, R&D, Research Triangle Park, North Carolina, USASearch for more papers by this authorJ Chism, J Chism GlaxoSmithKline, R&D, Research Triangle Park, North Carolina, USASearch for more papers by this authorA Choudhury, A Choudhury GlaxoSmithKline, R&D, King of Prussia, Pennsylvania, USASearch for more papers by this authorD J Nunez, D J Nunez GlaxoSmithKline, R&D, Research Triangle Park, North Carolina, USASearch for more papers by this author R L O'Connor-Semmes, Corresponding Author R L O'Connor-Semmes [email protected] GlaxoSmithKline, R&D, Research Triangle Park, North Carolina, USASearch for more papers by this authorJ Lin, J Lin GlaxoSmithKline, R&D, Research Triangle Park, North Carolina, USASearch for more papers by this authorR J Hodge, R J Hodge GlaxoSmithKline, R&D, Research Triangle Park, North Carolina, USASearch for more papers by this authorS Andrews, S Andrews GlaxoSmithKline, R&D, Research Triangle Park, North Carolina, USASearch for more papers by this authorJ Chism, J Chism GlaxoSmithKline, R&D, Research Triangle Park, North Carolina, USASearch for more papers by this authorA Choudhury, A Choudhury GlaxoSmithKline, R&D, King of Prussia, Pennsylvania, USASearch for more papers by this authorD J Nunez, D J Nunez GlaxoSmithKline, R&D, Research Triangle Park, North Carolina, USASearch for more papers by this author First published: 19 September 2014 https://doi.org/10.1038/clpt.2014.187Citations: 7Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract GSK2374697 is a genetically engineered fusion protein of a human domain antibody to exendin-4. This molecule binds with a high affinity to human serum albumin, creating a long-duration glucagon-like peptide-1 (GLP-1) receptor agonist. This study is the first evaluation of the albumin-binding domain antibody (AlbudAb) drug delivery platform in humans. The aim of this randomized clinical study was to determine the pharmacokinetics, pharmacodynamics, safety, and tolerability of GSK2374697. The pharmacokinetic profile was prolonged, with estimated half-lives ranging from 6 to 10 days. Postprandial glucose and insulin were reduced, and gastric emptying was delayed in healthy subjects, confirming anticipated GLP-1 receptor agonist pharmacology. The safety and tolerability were as expected for a potent GLP-1 agonist. Gradual titration of doses greatly improved tolerability. Rapid tolerance to nausea was observed. Study results support further investigation in type 2 diabetes and for weight loss. Clinical Pharmacology & Therapeutics (2014); 96 6, 704–712. doi:10.1038/clpt.2014.187 Citing Literature Volume96, Issue6Mitochondrial PharmacologyDecember 2014Pages 704-712 RelatedInformation
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