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

<p>  </p> <p>OBJECTIVE</p> <p>To evaluate the pharmacokinetics, pharmacodynamics, and safety of a novel U500 insulin aspart formulation (AT278 U500) compared with insulin aspart (IAsp U100).</p> <p>RESEARCH DESIGN AND METHODS</p> <p>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.</p> <p>RESULTS</p> <p>With AT278 U500, onset of appearance in serum was 6 min earlier (<em>P</em> <0.0001) and reached 50% of maximum concentration 23 min faster (<em>P</em> <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 (<em>P</em> <0.05). With AT278 U500, onset of action was 10 min earlier (<em>P</em> <0.0001) and reached 50% of maximum glucose infusion rate 20 min faster (<em>P</em> <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 (<em>P</em> <0.0001). Overall insulin exposure and glucose-lowering effect were comparable. No significant safety findings were observed.</p> <p>CONCLUSIONS</p> <p>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.</p>