URLi (LY900014), a novel ultra-rapid mealtime insulin in Phase 3 development, is shown to reduce postprandial glucose after subcutaneous injection. This 2-part, randomized, double-blind, Phase 1b study evaluated the differences in PK and PD between URLi and insulin lispro (Humalog®; HL) in 30 patients with T1D. Part A used a 6´period crossover design to evaluate safety and compare PK and postprandial glucose response to solid mixed meal tolerance tests (MMTT) with URLi or HL at different injection to mealtime intervals (-15, 0, and +15 min). Part B evaluated the safety, PK, and PD during 2 weeks of multiple daily dosing (immediately before a meal) in a parallel design. In Part A, URLi reduced glucose excursions (assessed as change in area under the concentration curve vs. time [∆AUC]) during the first 2 hours (∆AUC0-2h) and entire 5 hours (∆AUC0´5h) of the MMMT regardless of dose timing (Fig). URLi reduced ∆AUC0-2h by 103% (p=0.008), 39% (p=0.031), and 16% (p=0.096), and ∆AUC0-5h by 40% (p=NS), 44% (p=0.097), and 42% (p=0.026) vs. HL at -15, 0, and +15 min (significance level =0.1. The PK and PD profiles for URLi and HL were sustained after 2 weeks of outpatient dosing (Part B). Similar number of hypoglycemic events occurred between treatments during MMTTs. During 2 weeks of outpatient dosing, the number of events was lower for URLi vs. HL. Local tolerability was similar between treatments.
L. Plum-Moerschel: None. J. Leohr: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Employee; Spouse/Partner; Accenture. Stock/Shareholder; Spouse/Partner; Accenture. R. Liu: Employee; Self; Eli Lilly and Company. Employee; Spouse/Partner; Eli Lilly and Company. S. Reddy: None. M.A. Dellva: Employee; Self; Eli Lilly and Company. S. Lim: None. M. Loh: Employee; Self; Eli Lilly and Company. M.P. Knadler: Other Relationship; Self; Eli Lilly and Company. T. Hardy: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. C.M. Kazda: Employee; Self; Eli Lilly and Company.