Double-Blind Crossover Study of Ultra-Rapid AT247 Compared with NovoLog and Fiasp during Continuous Subcutaneous Infusion (CSII) Assessed by a Hyperinsulinemic Euglycemic Clamp

Background: AT247 is a novel insulin aspart formulation designed for ultra rapid absorption following subcutaneous injection to achieve optimal postprandial glycemic control. Method: Adults (29) with T1DM were randomized to 6 treatment sequences of AT247, Novolog (N), and Fiasp (F). Bolus (0.15 U/kg) and basal (0.02 U/kg/h) doses of insulin were administered via CSII for 3 days. PK and PD were assessed using euglycemic clamps on days (D) 1 and 3. Results: A higher early insulin exposure (AUCIns 0-30min mU/L/h) was observed for AT247 (16.7) vs N (6.3*) or F (13.0**) on D1, Fig 1A. The difference for AT247 was maintained on D3 (20.8) vs N (10.5*) but not vs F (19.2). A higher early glucose lowering effect (AUCGIR 0-60 mins mg/kg) was observed for AT247 (144.4) vs N (70.4*) but not vs F (145.8) on D1 only, Fig 1B. Time to early 50% Cmax insulin (h) occurred earlier for AT247 (0.18) compared to N (0.43*) and F (0.28**) on D1 and D3 (AT247 0.17; N 0.33**; F 0.22**). Statistical significance was p<0.05* or p<0.01**. AT247 was well tolerated with no significant adverse effects. Conclusions: The faster absorption of AT247 resulted in higher early insulin exposure than for F or N following bolus dose delivery during CSII. The demonstrated PK profile of AT247 supports further investigation into its potential to further improve automated insulin delivery. Disclosure M.Hompesch: Board Member; ProSciento, Consultant; Wiley-Blackwell, Employee; ProSciento, Stock/Shareholder; ProSciento. F.J.Lawrence: None. J.Jezek: None. D.J.Gerring: Employee; Arecor. T.Pieber: Advisory Panel; Arecor, Novo Nordisk A/S, Consultant; Lilly, Research Support; AstraZeneca, Novo Nordisk A/S, Sanofi, Speaker's Bureau; Roche Diagnostics.