Pharmacokinetic Properties of Fast-Acting Insulin Aspart Administered in Different Subcutaneous Injection Regions

Abstract

Background: Fast-acting insulin aspart (faster aspart) is insulin aspart set in a new formulation with faster initial absorption after subcutaneous administration. This study investigated the pharmacokinetic properties, including the absolute bioavailability, of faster aspart when administered subcutaneously in the abdomen, upper arm or thigh.

Methods: In a randomised, open-label, crossover trial, 21 healthy male subjects received a single injection of faster aspart at five dosing visits: 0.2 U/kg subcutaneously in the abdomen, upper arm and thigh, intramuscularly in the thigh and 0.02 U/kg intravenously. Blood sampling for pharmacokinetics was performed pre-dose and frequently thereafter until 12 h post-dose (8 h after intravenous administration).

Results: Onset of appearance (~3 min), time to 50% of maximum concentration (t Early 50% Cmax; ~20 min) and time to maximum concentration (t max; ~55 min) were all similar between injection regions. Early exposure within the first 2 h after injection (AUCIAsp,0-1h and AUCIAsp,0-2h) as well as maximum concentration (C max) were comparable for the abdomen and upper arm, but were ~25% lower for the thigh as seen previously for other mealtime insulin products. Total exposure (AUCIAsp,0-t) was similar for the abdomen, upper arm and thigh, and absolute bioavailability was ~80% after subcutaneous administration of faster aspart in all three injection regions.

Conclusion: The current study supports the ultra-fast pharmacokinetic characteristics of faster aspart across different injection regions, with administration in the abdomen and upper arm resulting in greater early exposure than in the thigh. ClinicalTrials.gov identifier: NCT02089451.

Conflict of interest statement

Funding

This study was funded by Novo Nordisk.

Conflict of interest

Tim Heise is a shareholder in Profil, which received research funds from Adocia, AstraZeneca, Becton Dickinson, Biocon, Boehringer Ingelheim, Dance Biopharm, Eli Lilly, Grünenthal, Gulf Pharmaceutical Industries, Johnson & Johnson, Marvel, MedImmune, Medtronic, Novartis, Novo Nordisk, Roche Diagnostics, Sanofi, Senseonics and Zealand Pharma. In addition, Tim Heise is a member of advisory panels for Novo Nordisk and received speaker honoraria and travel grants from Eli Lilly, Mylan and Novo Nordisk. Karen Margrete Due Thomsen and Hanne Haahr are employees and shareholders of Novo Nordisk. Ulrike Hövelmann, Leszek Nosek and Bettina Sassenfeld declare no conflicts of interest.

Figures

Fig. 1

Study design and subject disposition. Each subject participated in a total of five dosing visits in randomised sequence. All dosing visits were separated by a washout period of 3–12 days. The three randomised subjects who did not complete the trial were all due to withdrawal of consent (one before first dosing, one after subcutaneous administration in the thigh and one after intravenous administration and subcutaneous administration in the abdomen and upper arm). I.m. intramuscularly, i.v. intravenously, N number of subjects, s.c. subcutaneously

Fig. 2

Mean observed serum insulin aspart concentration-time profiles for 0.2 U/kg faster aspart administered subcutaneously in the abdomen, upper arm or thigh