Preclinical studies in animal models of obesity and inflammation have shown that oral administration of ARD-101, a potential TAS2R agonist, reduced food intake and body weight and downregulated inflammatory cytokines. We present results from a first-in-human phase 1 randomized, placebo-controlled trial that evaluated safety, pharmacokinetics, and pharmacodynamics of single or multiple ascending doses of oral ARD-101 (40, 100, and 240 mg) in healthy adults. A total of 43 subjects were randomly assigned and dosed to ARD-101 or placebo with 42 subjects completing the study treatment. ARD-101 was found to be99% restricted to the gut with minimal systemic exposure, demonstrated a favorable safety profile, and was well tolerated at all dose levels. Blood samples taken 1 hour after administration showed that subjects dosed with 240 mg of ARD-101 had elevated circulating levels of several gut peptide hormones. It is postulated that ARD-101 activates enteroendocrine cells to achieve its effects regulating metabolism and inflammation. The phase 1 clinical results demonstrated safety of ARD-101 and indicated activation of gut peptide hormone release in healthy adults. Further clinical trials will evaluate ARD-101 in patients with metabolic and inflammatory disorders.
