Ado09, A Co-Formulation Of The Amylin Analogue Pramlintide And The Insulin Analogue A21g, Lowers Postprandial Blood Glucose Versus Insulin Lispro In Type 1 Diabetes

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 mu g. 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 increment 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 ( increment 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.