114-LB: GX-G6, a Novel Long-Acting Glucagon-Like Peptide Receptor Agonist: Result of Phase I Study in Healthy Volunteers

Abstract

GLP-1 receptor agonists are widely used in T2DM. GX-G6 is a hyFcTM fused long acting GLP-1, and is a proposed alternative to other GLP-1 agents. In this phase I, randomized, double-blind, placebo-controlled, single ascending dose study, 8 subjects randomly received GX-G6 or its matching placebo in a 6:2 ratio, in each of 6 cohorts at 0.01, 0.02, 0.04, 0.08, 0.16 and 0.24 mg/kg. Primary endpoint was safety and tolerability. Pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity were also assessed. GX-G6 was well tolerated, and no subject experienced hypoglycemia. Decreased appetite was the most common treatment-emergent adverse event which resolved spontaneously without treatment. GX-G6 was rapidly absorbed and its average terminal half-life ranged 62-92 hours. AUC0-t and Cmax increased in dose-proportional manner. No dose dependency in plasma glucose level was observed in healthy subject setting. However, in the OGTT, tendency of decrease in glucose concentration compared to placebo was demonstrated at 0.5 hours. No subjects developed antibodies against GX-G6. Single SC doses of GX-G6 were safe and well-tolerated in a dose range of 0.01 to 0.24 mg/kg in healthy subjects. Dose dependent and durable PK profile and OGTT results show potentials of GX-G6 to be both weekly and twice-monthly treatment for T2DM. [Clinicaltrials.gov: NCT03651466]. Disclosure M. Byun: None. J. Woo: None. Y. Sung: None.