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.

Human sports drug testing by mass spectrometry

“…AOD-9604 was in clinical trials being developed as anti-obesity therapeutic (Halpern & Mancini, 2003;Mancini & Halpern, 2006) but desired effects remained modest under all investigated administration routes. Nevertheless, the substance was subjected to GRAS (Generally Recognized As Safe) assessment and received the respective status under conditions of intended use in foods, that is, for oral administration that was found to be well tolerated (Stier, Vos, & Kenley, 2013). The clandestine use of AOD-9604 (and other non-approved peptidic compounds) was uncovered in a recent anti-doping investigation (Harcourt, Marclay, & Clothier, 2014) and material was confiscated at various occasions (Vanhee et al, 2014), underlining the necessity of test methods for experimental drug candidates, requiring information on their metabolism and elimination in humans.…”

Safety and Metabolism of AOD9604, a Novel Nutraceutical Ingredient for Improved Metabolic Health

“…Two oral phase IIb studies with 300 and 500 obese adults were performed to assess efficacy (body mass reduction), safety and tolerability. In all human studies, AOD9604 was found to be safe and well tolerated [38]. Effects of AOD9604 on weight loss were seen in initial trials but were not seen in the last study in which an intensive diet and exercise regime was incorporated.…”

Identification and characterization of peptide drugs in unknown pharmaceutical preparations seized by the Belgian authorities: case report on AOD9604

“…Furthermore this peptide was also a subject of a sports scandal in an Australian football team . AOD9604 is currently being studied for its ability to reduce adipose fat tissue and could increase the power to weight ratios. For this reason the peptide is banned by the WADA under Section S0, indicating that the substance is still under pre‐clinical and clinical development and has not been approved for therapeutic use by any government health authority in the world…”