Search

Aim: To compare the safety, pharmacokinetics and pharmacodynamics of ADO09 with insulin lispro (Lispro) and separate subcutaneous injections of human insulin and pramlintide (Ins&Pram) in 24 subjects with type 1 diabetes. Methods: At three dosing visits, participants received single doses of ADO09, Ins&Pram or Lispro immediately before eating a standardized mixed meal together with 1 g of acetaminophen, which was used as a surrogate marker to evaluate the kinetics of gastric emptying. Premeal blood glucose was adjusted to 126 mg/dL ± 10% by means of insulin and glucose infusions. The insulin dose was 7.5 U and the pramlintide dose was 45 μg. Blood glucose, glucagon and acetaminophen concentrations were assessed as pharmacodynamic endpoints; insulin and pramlintide concentrations were analysed as pharmacokinetic endpoints, and safety and tolerability were assessed. Results: Compared with Lispro, ADO09 reduced postprandial blood glucose (ppBG) excursions by more than 95% in the first hour postmeal (mean ± SD ∆AUC BG 0‐1 h: 1.4 ± 9.9 mg*h/dL vs. 43.5 ± 15.3 mg*h/dL; p <.0001). Maximum ppBG was significantly improved with ADO09 (∆BGmax 87.0 ± 35.5 mg/dL) versus both Lispro (109.2 ± 31.1 mg/dL; p =.0133) and Ins&Pram (109.4 ± 44.3 mg/dL; p =.0357). Gastric emptying with ADO09 was similar to Ins&Pram and significantly slower than with Lispro. All treatments were well tolerated and both adverse events and hypoglycaemic events were rare during the meal test procedure. Conclusion: ADO09 was well tolerated and markedly reduced ppBG compared with Lispro. ADO09 formulation was generally similar to the separate administration of insulin and pramlintide, except for a better BG level in the 4‐8 h interval postmeal. These positive results warrant further investigations with ADO09. [ABSTRACT FROM AUTHOR]

We investigated the pharmacodynamics (PD) and pharmacokinetics (PK) of BioChaperone insulin Lispro (BCLIS), faster insulin aspart (FIA) and insulin aspart (ASP) in patients with type 1 diabetes using an insulin pump. In this randomized, double‐blind, three‐way crossover glucose clamp study, 43 patients received a bolus dose of each insulin (0.15 U/kg) in addition to a basal rate (0.01 U/kg/h), delivered via an insulin pump. With BCLIS, the AUC‐GIR,0–60 minutes (primary endpoint) was improved compared to ASP (least square means ratio, 1.63; 95% CI, 1.44–1.88; P < 0.0001) and was similar compared to FIA (least square means ratio, 1.06; 95% CI, 0.94–1.18; P = 0.4609). BCLIS showed faster‐on PD (tearly0.5GIRmax) than ASP and faster‐off PD (tlate0.5GIRmax) than both FIA and ASP. BCLIS also demonstrated significantly higher early exposure (AUCins, 0–60 minutes) and lower late exposure (AUCins,120–600 minutes) than both other insulins. In patients with type 1 diabetes using an insulin pump, BCLIS better mimics prandial insulin secretion and action than ASP and shows a faster off‐PD than FIA. [ABSTRACT FROM AUTHOR]