Safety and Efficacy of a Novel Glucagon Formulation in Type 1 Diabetic Patients Following Insulin-induced Hypoglycemia (AMG102)

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.

Study Overview

• Status: Completed
• Conditions: Hypoglycemia
• Intervention / Treatment: Drug: Nasal Glucagon 1 mg; Drug: Nasal Glucagon 2 mg; Drug: SC Glucagon; Drug: Nasal Glucagon 3 mg

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3P 3P1
      • Algorithme Pharma

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nasal Glucagon 1 mg; Nasal glucagon (NG) administered as single dose of 1 milligram (mg).	Drug: Nasal Glucagon 1 mg; Other Names: LY900018; Dry Powder Nasal Glucagon; AMG504-1
Experimental: Nasal Glucagon 2 mg; NG administered as single dose of 2 mg.	Drug: Nasal Glucagon 2 mg; Other Names: LY900018; Dry Powder Nasal Glucagon; AMG504-1
Active Comparator: SC Glucagon; Glucagon solution dose of 1 mg administered as a single subcutaneous (SC) injection.	Drug: SC Glucagon; Other Names: Glucagon; Glucagon for injection (rDNA origin)
Experimental: 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).	Drug: Nasal Glucagon 3 mg; Other Names: LY900018; Dry Powder Nasal Glucagon; AMG504-1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Responders	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.	Pre-dose; 30 minutes following glucagon administration
Number of Participants With at Least One Adverse Event	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.	Within 3 hours post glucagon administration

Secondary Outcome Measures

Outcome Measure	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: Locemia Solutions ULC

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: March 15, 2012
• First Submitted That Met QC Criteria: March 15, 2012
• First Posted (Estimate): March 16, 2012

Study Record Updates

• Last Update Posted (Actual): September 23, 2019
• Last Update Submitted That Met QC Criteria: September 5, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Hypoglycemia; Diabetes mellitus
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hypoglycemia; Physiological Effects of Drugs; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Glucagon; Glucagon-Like Peptide 1
• Other Study ID Numbers: 16416; I8R-MC-IGBA (Other Identifier: Eli Lilly and Company); AMG102 (Other Identifier: Locemia Solutions ULC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)