Comparative Pharmacokinetic/Pharmacodynamic Study of Liquid Stable Glucagon Versus Lyophilized Glucagon in Type 1 Diabetes Subjects

• Published in: Journal of diabetes science and technology 2016-09, Vol.10 (5), p.1101-1107
• Main Authors: Castle, Jessica R., Youssef, Joseph El, Branigan, Deborah, Newswanger, Brett, Strange, Poul, Cummins, Martin, Shi, Leon, Prestrelski, Steven
• Format: Article
• Language: English
• Subjects: Adult; Blood Glucose - drug effects; Cross-Over Studies; Diabetes Mellitus, Type 1 - drug therapy; Double-Blind Method; Female; Gastrointestinal Agents - administration & dosage; Gastrointestinal Agents - adverse effects; Gastrointestinal Agents - pharmacokinetics; Glucagon - administration & dosage; Glucagon - adverse effects; Glucagon - pharmacokinetics; Humans; Hypoglycemic Agents - administration & dosage; Insulin - administration & dosage; Insulin Infusion Systems; Male; Middle Aged; Original; Transdermal Patch; Young Adult
• ISSN: 1932-2968; 1932-2968; 1932-3107
• DOI: 10.1177/1932296816653141

Background: There is currently no stable liquid form of glucagon commercially available. The aim of this study is to assess the speed of absorption and onset of action of G-Pump™ glucagon at 3 doses as compared to GlucaGen®, all delivered subcutaneously via an OmniPod®. Methods: Nineteen adult subjects with type 1 diabetes participated in this Phase 2, randomized, double-blind, cross-over, pharmacokinetic/pharmacodynamic study. Subjects were given 0.3, 1.2, and 2.0 µg/kg each of G-Pump glucagon and GlucaGen via an OmniPod. Results: G-Pump glucagon effectively increased blood glucose levels in a dose-dependent fashion with a glucose Cmax of 183, 200, and 210 mg/dL at doses of 0.3, 1.2, and 2.0 µg/kg, respectively (P = ns vs GlucaGen). Mean increases in blood glucose from baseline were 29.2, 52.9, and 77.7 mg/dL for G-Pump doses of 0.3, 1.2, and 2.0 µg/kg, respectively. There were no statistically significant differences between treatments in the glucose T50%-early or glucagon T50%-early with one exception. The glucagon T50%-early was greater following G-Pump treatment at the 2.0 μg/kg dose (13.9 ± 4.7 min) compared with GlucaGen treatment at the 2.0 μg/kg dose (11.0 ± 3.1 min, P = .018). There was more pain and erythema at the infusion site with G-Pump as compared to GlucaGen. No serious adverse events were reported, and no unexpected safety issues were observed. Conclusions: G-Pump glucagon is a novel, stable glucagon formulation with similar PK/PD properties as GlucaGen, but was associated with more pain and infusion site reactions as the dose increased, as compared to GlucaGen.