231-OR: Phase I Study Investigating the PD, PK, and Safety of AT247 in Comparison with Novorapid and Fiasp

Background: AT247, an ultra-rapid acting formulation of insulin aspart designed for faster absorption following s.c. injection, will lead to better postprandial glycaemic control and is key to the development of closed-loop pump systems. Method: Plasma glucose and serum insulin concentrations were measured in 19 adult male participants with T1DM following a single s.c. dose (0.3 U/Kg) of insulin in a randomised, double-blind, cross over euglycaemic clamp study. Results: Data presented as median; range. AT247 had a faster onset of glucose lowering effect than NovoRapid® and Fiasp® (onset of action: 17; 12-30 vs. 37; 20-88 vs. 23;16-50 mins). The early glucose lowering effect was greater for AT247 than NovoRapid® and Fiasp® (AUCGIR 0-60min: 212; 63-465 vs. 49; 0-303 vs. 91; 11-300 mg/kg; GIR=glucose infusion rate) (Fig 1A). Similarly, greater initial insulin exposure was seen for AT247 compared to NovoRapid® and Fiasp® (AUC Insulin 0-60min: 111; 48-205 vs. 41; 12-147 vs. 66; 25-188 mU*h/L). In addition, offset of exposure occurred earlier for AT247 than NovoRapid® and Fiasp® (time to late 50% Cmax Insulin: 173; 89-414 vs. 212; 106-389 vs. 221;106-441 mins). (Fig 1B). Comparisons are statistically significant with p Conclusion: AT247 has a superior (left-shifted) time-action and time-concentration profile as compared to both NovoRapid® and Fiasp®. Disclosure T.R. Pieber: Advisory Panel; Self; ADOCIA, Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker’s Bureau; Self; Novo Nordisk A/S, Roche Diagnostics K.K. T. Augustin: None. C. Magnes: None. D.J. Gerring: None. J. Jezek: None. S.J. Howell: None. L. Zakrzewski: None. F.J. Lawrence: None. E. Svehlikova: None.