Abstrato

A study investigating the pharmacokinetic properties of insulin degludec/insulin aspart in healthy Chinese subjects

Shi Aixin, Li Yang, Xie Panpan, Qi Wenyuan, Yang Lei, Xu Hongfei, Zhang Ran, Hanne Haahr*

Objective: This study aimed to characterize the pharmacokinetic (PK) properties of the insulin degludec (degludec)/insulin aspart (IAsp) co-formulation (IDegAsp) in healthy Chinese subjects, and compare these with previous findings in Caucasian and Japanese subjects.

Methods: In this single-center, open-label study, 24 healthy Chinese adults received a single dose (SD) of IDegAsp (0.5 U/kg body weight). Regular blood sampling for serum IAsp and degludec measurements was performed for the first 20 hours, and less frequently up to 120 hours post-dose.

Results: Total exposure of IAsp (AUC_{IAsp,total,SD}) was estimated as 541 pmol·h/L (95% confidence interval [CI] 502;582), maximum concentration (C_max,IAsp,SD) as 217 pmol/L (95%CI 193;244), time to maximum concentration (t_max,IAsp,SD) as 1 hour, and onset of appearance as 14 min. Total exposure of degludec (AUC_{degludec,total,SD}) was estimated as 88,271 pmol·h/L (95%CI 83,615;93,187), maximum concentration (C_{max,degludec,SD}) as 3472 pmol/L (95%CI 3013;4002), and time to maximum degludec concentration (t_{max,degludec,SD}) as 10.5 hours. Importantly it should be noted that serum concentrations of degludec and IAsp cannot be directly compared and are not additive, as concentrations differ by several orders of magnitude due to the reversible binding of degludec to serum albumin. Six treatment-emergent adverse events occurred in three subjects; none were serious. The PK properties of IAsp and degludec were consistent with those observed in previous trials in Japanese and Caucasian subjects.

Conclusion: The rapid absorption of IAsp and the ultra-long PK profile of degludec were present in healthy Chinese subjects. The clinical benefits of IDegAsp observed in previous IDegAsp studies are expected in Chinese patients, and no specific IDegAsp dosing recommendations should be required. Clinicaltrials.gov identifier: NCT02844790