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Clinical Trial
. 2023 Apr 1;46(4):757-764.
doi: 10.2337/dc22-1054.

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

Eva Svehlikova  1 , Nicole L Ashcroft  2 , Christina Gatschelhofer  1 , David Gerring  2 , Vera Höller  1 , Jan Jezek  2 , Bettina Lackner  3 , Fiona Lawrence  2 , Vijay Pillai  2 , Maria Ratzer  3 , Martina Urschitz  1 , Michael Wolf  1 , Thomas R Pieber  1   3
Affiliations
Clinical Trial

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

Eva Svehlikova et al. Diabetes Care. .

Abstract

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 s.c.) in a crossover design, followed by an 8-h 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.

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Conflict of interest statement

Duality of Interest. The Medical University of Graz and Joanneum Research have received payment from the sponsor to conduct this research. N.L.A., D.G., J.J., F.L., and V.P. are employees of Arecor Limited. T.R.P. has received research support from AstraZeneca, Novo Nordisk, and Sanofi and has served on advisory panels for Arecor Limited, Eli Lilly and Company, Novo Nordisk, and Roche Diabetes Care. No other potential conflicts of interest relevant to this article were reported.

Figures

None
Graphical abstract
Figure 1
Figure 1
PK and PD of a novel U500 insulin aspart formulation (AT278 U500; orange line) and insulin aspart (IAsp U100; gray line) after s.c. administration of 0.3 units/kg in men with type 1 diabetes. Mean serum insulin aspart concentration-time profiles for 8 h (A) and 2 h (B) postdose and mean GIR-time profiles for 8 h (C) and 2 h (D) postdose. Variability bands show the SEM. Number of participants was 38 for both study medications.
See this image and copyright information in PMC

References

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