Pharmacokinetics, pharmacodynamics, andtolerability of JY09 in healthy Chinese subjects: A titrating, dose-escalating study.

Abstract

To evaluate the pharmacokinetics, pharmacodynamics, and tolerability of JY09, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, in healthy subjects. Healthy subjects were enrolled into 5 cohorts (0.3, 0.7, 1.5, 3.0, and 6.0 mg JY09) and received subcutaneous JY09 or placebo according to a randomized, double-blind, placebo-controlled, single-center, dose-escalating phase I trial design. Blood samples were collected over a 42-day period, and JY09 in plasma was determined by an electrochemical luminescence method. For the pharmacodynamic evaluation, oral glucose tolerance tests (OGTTs) were conducted predose and on day 5 after the target dose, during which plasma glucose, insulin, C-peptide, and glucagon concentrations were analyzed. Tolerability was assessed using physical examination and queries, vital sign measurements, laboratory analysis, and detection of immunogenicity. In healthy Chinese subjects, JY09 exhibited a dose-dependent increase in AUC0-inf and Cmax from 0.7to6.0 mg JY09. The half-life of JY09 was ~9.3 days, and the peak concentration was reached at ~60-72 hours. Following the OGTT, an increase in C-peptide concentration was observed after exposure to JY09 at the dose of 6.0mg compared to the placebo group. JY09 was well tolerated in healthy Chinese subjects following a single dose of up to 6.0mg. No symptomatic hypoglycemia was reported, and the most commonly observed adverse event was suppressed appetite, and its incidence was dose-dependent. Four subjects (13%) developed anti-JY09 antibodies. JY09 has a long half-life of ~9.3 days, with an acceptable safety profile.