Abstract

Objectives: To evaluate the pharmacokinetics, pharmacodynamics, and tolerability of JY09, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, in healthy subjects.
Materials and methods: 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.
Results: In healthy Chinese subjects, JY09 exhibited a dose-dependent increase in AUC_0–inf and C_max from 0.7 to 6.0 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 6.0 mg compared to the placebo group. JY09 was well tolerated in healthy Chinese subjects following a single dose of up to 6.0 mg. 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.
Conclusion: JY09 has a long half-life of ~ 9.3 days, with an acceptable safety profile.

#These authors contribute equally to this article.

Author Details

Authors

• Guangyu Yang^1,
• Bei Cao^1,
• Yuanxun Yang¹
• Yan Geng¹
• Hui Lin¹
• Junyi Jiang¹
• Yu Zhao¹
• Zuyi Weng¹
• Chen Zhang¹
• Yi Bai²
• Juan Li¹

Departments

• ¹ Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, and
• ²  Beijing Eastern Biotech, Co., Ltd., Beijing, China

Address


Junvi Li, PhD
Phase I Clinical Trial Unit, Nanjing Drum Tower Hospital, No. 321, Zhong Shan Road, Nanjing, 210008, China


and
Yi Bai
Beijing Eastern Biotech, Co., Ltd.
No.2 Rongjing Dong Street
Beijing Economic and Technolegical Development Zone
Beijing, China
Email: [email protected] and [email protected]

Citation