Pharmacokinetics and Pharmacodynamics of a Novel U500 Insulin Aspart Formulation: A Randomized, Double-Blind, Crossover Study in People With Type 1 Diabetes

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posted on 2023-01-30, 00:10 authored by Eva Svehlikova, Nicole L. Ashcroft, Christina Gatschelhofer, David Gerring, Vera Höller, Jan Jezek, Bettina Lackner, Fiona Lawrence, Vijay Pillai, Maria Ratzer, Martina Urschitz, Michael Wolf, Thomas R. Pieber

OBJECTIVE

To evaluate the pharmacokinetics, pharmacodynamics, and safety of a novel U500 insulin aspart formulation (AT278 U500) compared with insulin aspart (IAsp U100).

RESEARCH DESIGN AND METHODS

This single-center, randomized, double-blind study was conducted in 38 men with type 1 diabetes (body weight ≤100 kg and total insulin dose <1.2 units/kg/day). Participants received a single dose of either AT278 U500 or IAsp U100 (0.3 units/kg subcutaneously) in a crossover design, followed by an 8-hour euglycemic clamp in the absence of basal insulin.

RESULTS

With AT278 U500, onset of appearance in serum was 6 min earlier (P <0.0001) and reached 50% of maximum concentration 23 min faster (P <0.0001). Insulin exposure with AT278 U500 was 4.0-fold higher within the first 30 min (95% CI 3.29; 4.90), 1.5-fold higher within the first 60 min (95% CI 1.35; 1.76), and statistically superior up to 90 min postdose (P <0.05). With AT278 U500, onset of action was 10 min earlier (P <0.0001) and reached 50% of maximum glucose infusion rate 20 min faster (P <0.0001). The glucose-lowering effect with AT278 U500 was 8.9-fold higher within the first 30 min (95% CI 5.96; 17.46), 2.4-fold higher within the first 60 min (95% CI 1.92; 3.22), and statistically superior up to 2 h postdose (P <0.0001). Overall insulin exposure and glucose-lowering effect were comparable. No significant safety findings were observed.

CONCLUSIONS

AT278 U500 offers rapid-acting characteristics in a reduced dose volume, with accelerated absorption and onset of action compared with IAsp U100 in the studied population.