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

Phase 2

Completed

Interventions: Drug: SC Glucagon
Drug: Nasal Glucagon 1 mg
Drug: Nasal Glucagon 2 mg
Drug: Nasal Glucagon 3 mg

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
SC Glucagon	SC Glucagon	Glucagon solution dose of 1 mg administered as a single subcutaneous (SC) injection.
Nasal Glucagon 1 mg	Nasal Glucagon 1 mg	Nasal glucagon (NG) administered as single dose of 1 milligram (mg).
Nasal Glucagon 2 mg	Nasal Glucagon 2 mg	NG administered as single dose of 2 mg.
Nasal Glucagon 3 mg	Nasal Glucagon 3 mg	NG administered as single dose of 3 mg (composed of one dose of 1 mg NG immediately followed by one dose of 2mg NG).

Primary Outcome Measures

Name	Time	Method
Percentage of Responders	Pre-dose; 30 minutes following glucagon administration	Participants with a blood glucose increment of ≥1.5 millimole per liter \[mmol/L) within 15 of nadir (5 minutes post dose) and for at least 10 minutes following nadir.
Number of Participants With at Least One Adverse Event	Within 3 hours post glucagon administration	Safety and tolerability evaluated through the assessment of adverse events. An AE was defined as any untoward medical occurrence in a clinical investigation subject administered the investigational product and which did not necessarily have a causal relationship with this treatment. A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

Secondary Outcome Measures

Name	Time	Method
Maximum Concentration (Cmax) of Baseline-Adjusted Glucose	Pre-dose; 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2.0, 2.5 and 3.0 hours after glucagon administration
Time to Maximum Concentration (Tmax) of Baseline-Adjusted Glucose	Pre-dose; 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2.0, 2.5 and 3.0 hours after glucagon administration
Maximum Change From Baseline Concentration (Cmax) of Glucagon	Pre-dose; 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2.0, 2.5 and 3.0 hours after glucagon administration
Area Under the Curve (AUC0-last) of Baseline Adjusted Glucagon	Pre-dose; 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2.0, 2.5 and 3.0 hours after glucagon administration
Time to Maximum Concentration (Tmax) of Baseline Adjusted Glucagon	Pre-dose; 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2.0, 2.5 and 3.0 hours after glucagon administration