93-LB: A Randomized Clinical Trial of Safety, Pharmacokinetics, and Pharmacodynamics of Weekly Dosing Supagutide in Healthy Chinese Subjects

Abstract

Supaglutide (Supa) is a novel once-weekly, human-derived long-acting GLP-1 analogue developed for patients with type 2 diabetes. In this study, we investigated the safety, pharmacokinetics (PK) , pharmacodynamics (PD) and potential immunogenicity of single-dose subcutaneous injections of Supa in healthy subjects. In this double-blind, single dose-escalation, 14-week trial, 48 healthy subjects were randomized to subcutaneous Supa treatment (ranging from 0.375 to 9 mg) or placebo arms for 2 weeks. PK profile and safety parameters were assessed. PD parameters (glucose and insulin concentrations) were measured following an oral glucose tolerance test (OGTT) (Day 3) . The half-life of Supa was approximately 120 h with a median Tmax ranging from 48 to 72 h (Table 1) . Supa treatment significantly reduced body weight compared to placebo in a dose-dependent and time-dependent fashion. OGTT results showed that Supa at all doses investigated significantly decreased glucose levels during the test, suggesting increased glucose tolerance. Supa was safe and well-tolerated in healthy subjects with some increase in mild to moderate gastrointestinal symptoms with escalating doses. No subjects developed anti-Supa antibodies. The safety, PK and PD profiles supported Supa as a long-acting injectable medication for glycemic control and weight loss, as an alternative GLP-1 therapy. Disclosure A. Ma: None. J. Li: None. G. J. Prud’homme: None. D. Zhu: n/a. Q. Wang: None. Y. Zhou: None. Y. Lou: None. Y. Liao: None. A. Shao: None. Z. Wang: None. Y. Jiang: None. Q. Cui: None. Y. Zhao: None. Funding Ministry of Science and Technology (No. 2011ZX09102, No. 2017ZX09303001) , Shanghai Science and Technology Department (No. 2017ZX09303001)