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. Disclosure S. Thohan: None. W.T. Hu: None. M.J. Donovan: None. S.J. Prestrelski: Employee; Self; Xeris Pharmaceuticals, Inc. M.S. Choi: None. D.M. Hester: None.
Insulin therapy is the primary treatment option for patients with type 1 and 2 diabetes. Despite considerable advances in insulin chemistry, delivery, and pharmacology, only a small percentage of diabetic patients achieve near normal glycemic levels. Xeris has developed novel room temperature stable insulin formulations that may offer duration of efficacy advantages over commercially available options. 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). XeriSol™ insulins showed comparable efficacy and pharmacokinetic profiles commercial products with up to 4 hours of glycemic control. Xerisol formulations of Insulin and Lispro showed trends for lower sustained means (30-240 min) for glucose levels and slightly longer half-lives than comparative doses of commercial Humulin and Humalog. Disclosure S. Thohan: None. M.J. Donovan: None. W.T. Hu: None. M.S. Choi: None. D.M. Hester: None. S.J. Prestrelski: Employee; Self; Xeris Pharmaceuticals, Inc.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.