Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans

Abstract

Background: The human growth hormone (hGH) has properties making it a potential candidate to treat obesity, however safety issues limit its long-term use. AOD9604 is a peptide fragment of the C-terminus of hGH (Tyr-hGH 177-191 ), which harbors the fat reducing activity of hGH, without its negative effects. In this paper the safety data of AOD9604 obtained in clinical trials are summarized. Methods: Six randomized, double-blind, placebo-controlled trials were performed with AOD9604. Special focus was given to undesired effects associated with hGH treatment: increases in IGF-1 levels, insulin resistance, and impaired glucose tolerance. Blood samples were analyzed for presence of anti-AOD9604 antibodies to exclude immunogenicity. Results: AOD9604 had no effect on serum IGF-1 levels, which confirms the hypothesis that AOD9604 does not act via IGF-1. Results of oral glucose tolerance test demonstrated that, in contrast with hGH, AOD9604 has no negative effect on carbohydrate metabolism. There were no anti-AOD9604 antibodies detected in any of the patients selected for antibody assay. In none of the studies did a withdrawal or serious adverse event occur related to intake of AOD9604. Conclusion: AOD9604 displayed a very good safety and tolerability profile indistinguishable from placebo. AOD9604 did not result in any of the adverse effects associated with full-length hGH treatment. J Endocrinol Metab. 2013;3(1-2):7-15 doi: https://doi.org/10.4021/jem157w