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GSK2374697, a Novel Albumin‐Binding Domain Antibody (AlbudAb), Extends Systemic Exposure of Exendin‐4: First Study in Humans—PK/PD and Safety
Author(s) -
O'ConnorSemmes R L,
Lin J,
Hodge R J,
Andrews S,
Chism J,
Choudhury A,
Nunez D J
Publication year - 2014
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2014.187
Subject(s) - tolerability , pharmacokinetics , agonist , pharmacology , pharmacodynamics , postprandial , glucagon like peptide 1 receptor , gastric emptying , clinical pharmacology , medicine , albumin , receptor , chemistry , adverse effect , insulin , stomach
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