Clinical Usability of Intranasal Glucagon in Treatment of Hypoglycemia

A Multiple Center, Open Label, Prospective, Observational Study to Evaluate the Effectiveness and Ease-of-Use of AMG504-1 Administered in the Home or Work Environments for Treating Episodes of Hypoglycemia in Patients With Type 1 Diabetes

Up to two hundred (200) adult participants with type 1 diabetes (T1D) aged 18 to 75 years will be selected for inclusion in the study. The target is to obtain treatment response and user-experience data following use of nasal glucagon (AMG504-1) in treating episodes of hypoglycemia. The population will be enriched to include participants who suffer from impaired hypoglycemia awareness.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus; Hypoglycemia; Drug-Specific Antibodies
• Intervention / Treatment: Drug: Nasal Glucagon

Detailed Description

This study is designed to evaluate the effectiveness of nasal glucagon (NG) administered under clinical use conditions in treating episodes of hypoglycemia in persons with T1D.

This study also aims to assess the ease with which caregivers can administer the experimental medication in treatment of hypoglycemic events.

The study will also generate data on the participants' assessment of local tolerability and provide information on immunogenicity of nasal glucagon with regards to the potential development of anti-glucagon antibodies.

• Study Type: Interventional
• Enrollment (Actual): 129
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4G2
    • Centre Hospitalier de l'Université de Québec
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3C 0N2
      • Winnipeg Clinic
  • Ontario
    • Smiths Falls, Ontario, Canada, K7A 4W8
      • Diabetes Clinic
  • Quebec
    • Montreal, Quebec, Canada, H2W 1R7
      • IRCM
    • Sherbrooke, Quebec, Canada, J1G 5K2
      • Centre de recherche d'endocrinologie Godin & St-Pierre
    • Westmount, Quebec, Canada, H3Z 1E5
      • Applied Medical Informatics Research
• United States
  • Massachusetts
    • Waltham, Massachusetts, United States, 02451-1136
      • New England Diabetes and Endocrinology Center (NEDEC)
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • New York
    • Albany, New York, United States, 12206
      • Albany Medical College Division of Community Endocrinology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or Female Person with diabetes (PWD) lives with or is in frequent contact with one or more caregivers who are available to administer the glucagon in case of an episode of severe or moderate hypoglycemia
• With a history of type 1 diabetes >1 year
• At least 18 years of age but not older than 75 years
• Body mass index (BMI) greater than or equal to 18.50 and below 35.00 kg/m2.
• PWD will be otherwise healthy according to medical history, general physical examination (including vital signs), nasal examination, and laboratory tests (biochemistry, hematology, and urinalysis).
• For female subjects, a urine pregnancy test must be negative.

Exclusion Criteria:

• Presence or history of pheochromocytoma (i.e. adrenal gland tumor) or insulinoma.
• Use of a daily systemic beta-blockers, indomethacin, warfarin or anticholinergic drugs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nasal glucagon; 3 mg nasal glucagon powder delivered using a nasal powder dosing device.	Drug: Nasal Glucagon; 3 mg nasal glucagon powder; Other Names: LY900018; AMG504-1; Dry-Mist Nasal Glucagon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Awakening or Returning to a Normal Status Within 30 Minutes Following Studied Drug of Administration	Responses to questions completed by the caregiver were used to assess this outcome. An episode of severe hypoglycemia was defined as an episode wherein the person with diabetes is clinically incapacitated to the point where the person requires third-party assistance to treat the hypoglycemia. An episode of moderate hypoglycemia episode was defined as an episode wherein the person with diabetes was showing signs of neuroglycopenia and had a glucometer reading of approximately 60 milligrams per deciliter (mg/dL) (3.3 millimoles per liter [mmol/L]) or less based on a blood sample taken at or near the time of treatment.	Within 30 minutes after each drug administration for an episode of hypoglycemia

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver	Measurement for Degree of difficulty: opening the kit, Degree of difficulty: understanding the instructions on how to use the kit, Degree of difficulty: administering the medication into the nostril, Degree of satisfaction is 1 (Very Difficult) to 7 (Very Easy). Measurement for Dry Mist Nasal Glucagon will be easy to teach other caregivers, Nasal formulation of glucagon is less intimidating for caregivers, Nasal Glucagon is easy to carry and would be willing to carry it, nasal delivery of glucagon is preferable. Level of agreement 1 (Strongly Disagree) to 7 (Strongly Agree).	After each drug administration for an episode of hypoglycemia
Percentage of Participants With Adverse Events (AEs) Reported Through the Nasal Score Questionnaire	Adverse events solicited through the Nasal Score Questionnaire included: runny nose, nasal congestion (nostrils plugged), nasal itching, sneezing, watery eyes, itchy eyes, redness of eyes, itching of ears, itching of throat, and other. A summary of other nonserious AEs, and all Serious Adverse Events (SAEs), regardless of causality, is located in the Reported Adverse Events section.	Within 2 hours of full recovery from a hypoglycemic event

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Glucose Levels Over Time	The participants' blood glucose level was measured by the caregiver using a glucometer at baseline (just prior to dosing and right after the study drug administration), 15, 30 and 45 minutes after nasal glucagon administration.	Baseline (just prior to dosing or right after study drug administration) , 15, 30 and 45 minutes after drug administration for an episode of hypoglycemia
Number of Participants With Treatment-Emergent Glucagon Anti-Drug Antibodies (ADA)	Treatment-Emergent ADA includes treatment-induced ADA ('Not Detected' ADA at baseline and at least one post-baseline 'Detected' ADA sample with a corresponding titer of (1:20) and treatment-boosted ADA (with 'Detected' ADA at baseline and at least one post-baseline 'Detected' ADA sample with a corresponding titer that is at least 4-fold higher than the baseline titer.	Baseline and End of Study (6 months)

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: June 12, 2014
• First Submitted That Met QC Criteria: June 20, 2014
• First Posted (Estimate): June 24, 2014

Study Record Updates

• Last Update Posted (Actual): October 15, 2019
• Last Update Submitted That Met QC Criteria: September 27, 2019
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Hypoglycemia; Diabetes Mellitus; Immunogenicity; Glucagon; Anti-glucagon Antibody
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hypoglycemia; Physiological Effects of Drugs; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Glucagon; Glucagon-Like Peptide 1
• Other Study ID Numbers: 16427; I8R-MC-B002 (Other Identifier: Eli Lilly and Company); AMG108 (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 Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.