A Single Center, Open-Labeled Trial to Investigate the Pharmacokinetics of Insulin Detemir in Healthy Taiwanese Subjects

Abstract

Backgrounds: Insulin detemir (NN304) is a long-acting insulin analogue reported to provide more predictable blood glucose level throughout the day, leading to a lower within-subject variability compared to NPH insulin. Pharmacokinetic profiles of insulin detemir had not been investigated in Taiwanese. This study was to determine whether there is a difference between Taiwanese subjects in pharmacokinetic profile of insulin detemir compared to Caucasian subjects. Methods: Pharmacokinetic profile of insulin detemir was measured in twenty male Taiwanese (NN304-3023). Eligible subjects were given insulin detemir as a single dose subcutaneous injection at 0.5 U/kg body weight in the mid-thigh using NovoPen® 3 device. 32-hour serum insulin detemir concentrations were measured. Hypoglycemia and other adverse events were recorded. The results were compared to data obtained from a previous trial in Caucasian subjects (NN304-1451). Results: There was no significant difference between Taiwanese (NN304-3023) and Caucasian (NN304-1451) in the primary endpoint, AUC(0–∞) , and the secondary endpoints, AUC(0–24h), and t1/2. However, the secondary endpoints, Cmax was 40% higher, tmax was shorter (270.0 vs 420.0 min) and AUC(0–5h) was 2-fold more in Taiwanese. When only male subjects were included in the comparator trial (NN304-1451), the t1/2 was significantly shorter in Taiwanese (348 min vs 404 min). There was no significant difference in the mean blood glucose concentrations between Taiwanese and Caucasian subjects. A single episode of hypoglycemia (53 mg/dL) was reported in a 24-year-old male approximately 2.5 hours after the administration of insulin detemir. He was able to treat himself for the episode. Conclusion: In this pharmacokinetic evaluation of a single dose administration of insulin detemir in Taiwanese male subjects, the AUC(0–∞) , and AUC(0–24h) were not different from that of Caucasians in the comparator trial. However, insulin detemir appeared to be more rapidly absorbed in Taiwanese males. Further studies are warranted to elucidate its pharmacodynamic response and mechanisms. Finally, there was no clinically relevant safety concern raised in this study (Funded by research grant from Novo Nordisk, Taiwan, first registration (22/12/2011) ClinicalTrials.gov number, NCT01497587).