Safety, Pharmacokinetics and Pharmacodynamics of Multiple Escalating Doses of PEGylated Exenatide (PB-119) in Healthy Volunteers.

BACKGROUND AND

objectiveAt present, the deficiency of β-cell function is progressive in patients with type 2 diabetes mellitus. Exenatide cannot only control blood glucose well, but also promotes the regeneration and proliferation of islet β-cells and improves the function of β cells. However, it needs to be given twice a day, and there are many adverse reactions such as nausea. PEGylated exenatide (study code: PB-119) needs to be administered only once a week. The purpose of this experiment was to evaluate the safety, pharmacokinetics and pharmacodynamics of an escalating dose regimen of subcutaneous PEGylated exenatide injections in healthy subjects.

methodsTwelve healthy young adult subjects in each group received once-weekly subcutaneous injections of 165 μg, 330 μg, and 660 μg PEGylated exenatide for 6 weeks. Plasma drug concentration was determined in venous blood collected across selected time points. Safety and tolerability were evaluated by monitoring adverse events, laboratory parameters, and electrocardiogram. Blood glucose, insulin,  glucagon and C peptide were monitored at different time points to evaluate the pharmacodynamics of PEGylated exenatide.

resultsA total of 11, 10, and 12 subjects completed the study in 165 µg, 330 µg, and 660 µg dose groups, respectively. After 6 consecutive weeks of administration, the t

conclusionA once-weekly subcutaneous injection of 165 µg and 330 µg PEGylated exenatide is safe. No significant effects on blood glucose or pancreatic hormone levels were observed in the subjects within these dose groups. The pharmacokinetic parameters of PEGylated exenatide may be affected by immunogenicity. CLINICAL TRIALS REGISTRATION: The study is registered at clinicaltrials.gov (No. NCT03062774).