811-P: Once-Weekly Insulin SHR-3167 vs. Insulin Glargine U100 (IGlar U100) in Healthy Subjects

by sugaradmin



Introduction and Objective: This trial assessed the PD, PK, and safety of SHR-3167 vs IGlar U100 in healthy subjects.Methods: This was an open-label, two-period, single-sequence trial. Sixteen healthy males were enrolled into two cohorts. Both cohorts received a single injection of IGlar U100 (0.4 U/kg), following a 7-day washout, and then received a single injection of SHR-3167 at 0.3 and 0.6 mg/kg, respectively. Subjects underwent a 24-h euglycemic glucose clamp on Day 1 after IGlar U100 injection, and three clamps after SHR-3167 injection including a 24-h clamp on Day 7. Primary endpoint was the area under the curve for glucose infusion rate (AUCGIR).Results: In each cohort, eight subjects received IGlar U100, and seven received SHR-3167. Mean coefficient of variation in blood glucose (BG), deviation from the target BG, and rate of off-target in BG during the clamp were 3.9%, 3.1%, and 1.6% for IGlar U100, 2.8%, 2.5%, and 0.1% for SHR-3167 at 0.3 mg/kg, and 3.4%, 2.5%, and 1.6% for SHR-3167 at 0.6 mg/kg with high clamp quality. C-peptide levels were consistently lower than baseline levels during all the clamp periods. Mean AUCGIR,0-24h was 3357.6 mg/kg for IGlar U100 on Day 1, 1889.7 mg/kg for SHR-3167 at 0.3 mg/kg, and 3546.8 mg/kg for SHR-3167 at 0.6 mg/kg on Day 7, indicating an approximately linear dose-glucose-lowering effect for SHR-3167, and showing similar AUCGIR between SHR-3167 at 0.6 mg/kg and IGlar U100. Cmax of SHR-3167 was achieved at 3 days, and the geomean t1/2 was 10.8 to 12.1 days. The Cmax and AUC0-∞ of SHR-3167 were 27.4 nmol/L and 593 day*nmol/L at 0.3 mg/kg, and 55.5 nmol/L and 1050 day*nmol/L at 0.6 mg/kg. SHR-3167 exposure increased proportionally within the investigated dose range. Only one subject who received SHR-3167 at 0.6 mg/kg reported asymptomatic hypoglycemia. SHR-3167 was safe and well tolerated.Conclusion: The PD/PK profiles, and safety of SHR-3167 support its potential as once-weekly regimen for glycemic management.

Disclosure

C. Tang: None. L. Wan: None. H. Chen: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. X. Wu: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. K. Shen: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. Y. Dong: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. Y. Ma: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Funding

Jiangsu Hengrui Pharmaceuticals Co., Ltd (sponsor)



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