Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a well-characterized and effective class of glucose-lowering agents for the treatment of patients with type 2 diabetes mellitus (T2DM) . To date, all market-authorized GLP-1 RAs are peptides, and only one is administered orally. RGT-075 is a novel, orally bioavailable, small-molecule GLP-1 RA which has shown therapeutic potential in animal models of T2DM. The results of a first-in-human study of RGT-075 are presented.

Methods: A phase 1, randomized, double-blind, placebo-controlled study was conducted to investigate the safety, tolerability, and pharmacokinetics of single escalating oral doses of RGT-075 (15-280 mg) in healthy adult volunteers. Seven cohorts of 8 subjects were enrolled and randomized to treatment with RGT-075 or matching placebo (6 active/2 placebo per cohort) . Plasma and urine samples were collected over 48 hours post-dose and analyzed for RGT-075 concentrations.

Results: A total of 56 healthy adults (64% male, mean age 42.5 years) participated in the study. Treatment-emergent adverse events (TEAEs) were reported by 28 of 56 (50%) subjects (24 subjects treated with RGT-075 and 4 subjects treated with placebo) . There were no serious adverse events, deaths or TEAEs that led to early withdrawal. The majority of TEAEs were considered mild, and the most common TEAEs related to study drug were nausea, vomiting, and headache. Maximum tolerated dose was not reached. Single oral doses of RGT-075 (15-280 mg) resulted in linear increases in Cmax, AUClast, and AUCinf with ascending doses through 240 mg. Mean elimination half-life ranged from 6.3-11.7 hours. Renal clearance of RGT-075 was low to negligible.

Conclusion: Overall, single RGT-075 doses between 15-280 mg were safe and well-tolerated in healthy volunteers. Further clinical development of RGT-075 as a once-daily, oral therapy for T2DM is underway.


M.A.Pirner: Employee; Regor Pharmaceuticals, Inc. J.Lin: None. F.Liu: Employee; Regor Pharmaceuticals Inc. L.Yao: None. M.E.Zettler: Employee; Cardinal Health, Regor Pharmaceuticals Inc. D.J.Valacer: Employee; Regor Pharmaceuticals, Inc.

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