Safety and Efficacy of a Novel Glucagon Formulation in Type 1 Diabetic Patients Following Insulin-induced Hypoglycemia

Phase II Study to Investigate the Safety and Efficacy of 2 Dose Levels of a Novel Glucagon Formulation Compared to Commercially Available Glucagon in Type 1 Diabetic Patients Following Insulin-induced Hypoglycemia

In this study, participants with Type 1 diabetes received insulin through an infusion into a vein to reduce their blood glucose, and then received nasal glucagon (NG) or glucagon for injection under the skin, and their blood glucose was measured for 3 hours.

The main objective of this study was to evaluate the safety and efficacy of intranasal and subcutaneous glucagon (SC) in reversing insulin-induced hypoglycemia in participants with type 1 diabetes.

In the study, up to four (4) treatments were administered as a single dose either intranasally or subcutaneously to eighteen (18) male or female participants under fasting conditions and following the use of insulin to lower blood glucose. The participants were assigned at random to a group that received one treatment for each of the 3 study periods. The glucagon administrations were separated by approximately 7 calendar days. For 2 participants, a single dose of 3 mg NG was administered at the 4th period that was separated by at least 21 calendar days from the 3rd period.

Inclusion Criteria:

• History of type 1 diabetes between 2 and 30 years
• Receiving daily insulin injections or insulin pump therapy for at least 2 years
• If patient is taking Lantus, Levemir or equivalent once-daily in the evening as basal insulin, must be willing to transition to once-daily in the morning at least 48 hours prior to 1st dosing, and to follow this dosing regimen for the entire duration of the study
• Body mass index (BMI) greater than or equal to 20.00 and below or equal to 33.00 kg/m2
• Female patients must not be pregnant, and must be using effective contraception.
• Light-, non- or ex-smokers. A light smoker is defined as someone smoking 10 cigarettes or less per day for at least 3 months before day 1 of this study. An ex smoker is defined as someone who completely stopped smoking for at least 6 months before day 1 of this study

Exclusion Criteria:

• History of an episode of severe hypoglycemia (as defined by an episode that required third party assistance for treatment) in the previous 6 months before day 1 of this study
• Score ≥4 on the Clarke Hypoglycemia Awareness survey at screening
• Presence or history of pheochromocytoma (i.e. adrenal gland tumor)
• Presence or history of significant upper respiratory or allergic (i.e., seasonal rhinitis) disease
• Presence of clinically significant findings on nasal examination and bilateral anterior rhinoscopy
• Known presence of hereditary problems of galactose and /or lactose intolerance
• History of significant hypersensitivity to glucagon or any related products as well as severe hypersensitivity reactions (like angioedema) to any drugs