2483-PUB: Glycemic Control with Pramlintide and Insulin Coformulations: Preclinical Evaluation of a Novel Single Injection, Room Temperature Stable Formulation

Mealtime pramlintide (PRAM) and insulin (INS) reduce postprandial glucose excursions, mimics natural pancreas physiology and improves glycemic control. Due to differences in physico-chemical characteristics of PRAM and INS, mixing these two products can cause precipitation. Xeris has developed novel room temperature stable co-formulations to overcome precipitation, simplify dose administration and reduce injection burden. Streptozotocin (65 mg/kg) treated SD rats were given co-formulations of PRAM and Regular Insulin (RI) or Lispro Insulin (LISPRO) as a single injection and compared with dual injection of commercial Symlin, Humulin, or Humalog. Blood samples were evaluated for plasma glucose and PK. A sparse sampling PK scheme resulted in ∼30% CV for glucose values. Mean glucose profiles with reductions in glucose AUC by treatment (efficacy). PRAM-INS single injection co-formulations showed comparable efficacy and PK profiles to two injection commercial products. Consistent with PRAM's known pharmacological action, there was no glucose lowering with PRAM alone. These results support clinical development of room temperature stable PRAM-INS co-formulations.