Clinical Usability of Nasal Glucagon in Treatment of Hypoglycemia in Children and Adolescents

A Multiple Center, Open Label, Prospective Study to Evaluate the Effectiveness and Ease-Of-Use of AMG504-1 Administered in the Home or School Environments for Treating Hypoglycemia in Children and Adolescents With T1D

Up to fifty (50) children and adolescents with type 1 diabetes (T1D) aged 4 to ˂18 years at time of enrolment will be selected for inclusion in the study. The target is to obtain treatment response and user-experience data following use of Nasal Glucagon (LY900018) in treating episodes of hypoglycemia.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus; Hypoglycemia
• 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 moderate or severe 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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tallahassee, Florida, United States, 32308
      • Private Clinic
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • Private Clinic
  • Massachusetts
    • Waltham, Massachusetts, United States, 02451-1136
      • New England Diabetes and Endocrinology Center (NEDEC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Availability for the entire study period.
• Motivated Child/Adolescent with diabetes (C/AWD) and caregiver(s) and absence of intellectual problems likely to limit the validity of consent to participate in the study or the compliance with protocol requirements; ability to cooperate adequately; ability to understand and observe the instructions of the qualified investigator or designee.
• C/AWD lives with one or more caregivers who are available to administer the glucagon in case of an episode of severe or moderate hypoglycemia.
• Male or female C/AWD with a history of type 1 diabetes >1 year.
• C/AWD aged of at least 4 years of age but less than 18 years.

• A female C/AWD must meet one of the following criteria:

  a) Participant is of child-bearing potential and agrees to use one of the accepted contraceptive regimens throughout the entire duration of the study (from the pre-trial evaluation and enrollment visit until study completion). An acceptable method of contraception includes one of the following: (i) Abstinence from heterosexual intercourse (ii) Systemic contraceptives (birth control pills, injectable/implantable/ insertable hormonal birth control products, transdermal patch) (iii) Intrauterine device (iv) Condom with spermicide, OR b) Participant is of non-child-bearing potential, defined as a female who had had a hysterectomy or tubal ligation, is clinically considered infertile or has not yet reached menarche.

• In good general health with no conditions that could influence the outcome of the trial, and in the judgment of the Investigator is a suitable candidate for the study based on review of available medical history, physical examination and clinical laboratory evaluations.
• Willingness to adhere to the protocol requirements.

Exclusion Criteria:

• Females who are pregnant according to a positive urine pregnancy test, actively attempting to get pregnant, or lactating.
• History of significant hypersensitivity to glucagon, or any related products as well as severe hypersensitivity reactions (such as angioedema) to any drugs.
• Presence of cardiovascular, gastrointestinal, liver or kidney disease, or any other conditions which in the judgment of the investigator could interfere with the absorption, distribution, metabolism or excretion of drugs or could potentiate or predispose to undesired effects.
• Presence or history of pheochromocytoma (i.e. adrenal gland tumor) or insulinoma.
• Use of daily systemic beta-blockers, indomethacin, warfarin or anticholinergic drugs.
• Concomitant maintenance therapy with any drug that would influence the outcome of the trial, at the discretion of the Investigator and the Sponsor.
• Regular consumption of 3 or more units of alcoholic beverages per day.
• Current participation in another clinical trial, intent to enroll in another clinical trial during this clinical study or use of an Investigational Product (in another clinical trial) within the prior 30 days.

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; A single dose of 3mg glucagon nasal powder administered using a nasal powder delivery device for the treatment of moderate or severe hypoglycemic events; a maximum of 4 events per participant during the study.	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
Number of Participants Awakening or Returning to a Normal Status Within 30 Minutes Following Studied Drug of Administration	Responses to questions completed by the caregiver are used to assess this outcome. An episode of severe hypoglycemia is generally defined as an event associated with severe neuroglycopenia usually resulting in coma or seizure and requiring parenteral therapy (glucagon or intravenous glucose) administered by a third party. In this study moderate hypoglycemia is defined as an episode wherein the child/adolescent with diabetes has symptoms and/or signs of neuroglycopenia and has a blood glucose ≤3.9 millimoles per liter (mmol/L) (70 milligram per deciliter [mg/dL]) based on a blood sample taken at or close to 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 by Completion of Questionnaire by the Caregiver	Assess ease-of-use of intranasal administered glucagon in the hands of caregivers of participants who may be called upon to treat episodes of hypoglycemia. 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, Dry Mist Nasal Glucagon is easy to carry and would be willing to carry it, Intranasal 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 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 non-serious AEs, and all SAE's, 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
Change in Blood Glucose Level Over Time	Glucometer-based measurements of blood glucose after the studied drug administration. The participants' change in blood glucose level from baseline (just prior to dosing or right after the study drug administration) was measured by the caregiver using a glucometer at 15, 30 and 45 minutes after NG administration. The change in glucose was calculated from each time point (15, 30 and 45 minutes) minus the baseline.	Baseline (just prior to dosing or right after study drug administration), 15, 30 and 45 minutes after drug administration for an episode of hypoglycemia

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: March 25, 2015
• First Submitted That Met QC Criteria: March 25, 2015
• First Posted (Estimate): March 30, 2015

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

• 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: 16423 (Other Identifier: City of Hope Medical Center); I8R-MC-B001 (Other Identifier: Eli Lilly and Company); AMG109 (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)