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

NCT01556594 | Completed Phase 2 Results

• 3 other identifiers: 16416I8R-MC-IGBAAMG102
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypoglycemia

Keywords

Hypoglycemia; Diabetes mellitus

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• 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

Study Arms (4)

Nasal Glucagon 1 mg

EXPERIMENTAL

Nasal glucagon (NG) administered as single dose of 1 milligram (mg).

Drug: Nasal Glucagon 1 mg

Nasal Glucagon 2 mg

EXPERIMENTAL

NG administered as single dose of 2 mg.

Drug: Nasal Glucagon 2 mg

SC Glucagon

ACTIVE COMPARATOR

Glucagon solution dose of 1 mg administered as a single subcutaneous (SC) injection.

Drug: SC Glucagon

Nasal Glucagon 3 mg

EXPERIMENTAL

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

Interventions

Nasal Glucagon 1 mg DRUG

Also known as: Dry Powder Nasal Glucagon, AMG504-1, LY900018

Nasal Glucagon 1 mg

Nasal Glucagon 2 mg DRUG

Also known as: Dry Powder Nasal Glucagon, AMG504-1, LY900018

Nasal Glucagon 2 mg

SC Glucagon DRUG

Also known as: Glucagon, Glucagon for injection (rDNA origin)

SC Glucagon

Nasal Glucagon 3 mg DRUG

Also known as: Dry Powder Nasal Glucagon, AMG504-1, LY900018

Nasal Glucagon 3 mg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead
• Locemia Solutions ULC: collaborator

Study Sites (1)

Algorithme Pharma

Montreal, Quebec, H3P 3P1, Canada

Location

MeSH Terms

Conditions

Hypoglycemia; Diabetes Mellitus

Interventions

Glucagon; Injections

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Proglucagon; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Drug Administration Routes; Drug Therapy; Therapeutics

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2012
• First Posted: March 16, 2012
• Study Start: March 1, 2012
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: September 23, 2019
• Results First Posted: August 13, 2014

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• 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.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

Locations

CA (1)