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Assessment of Intranasal Glucagon in Children and Adolescents With Type 1 Diabetes

Primary Purpose

Diabetes Mellitus, Type 1

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Nasal Glucagon

Intramuscular Glucagon

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 1

Eligibility Criteria

4 Years - 16 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

To be eligible, the following inclusion criteria were met:

History of type 1 diabetes and receiving daily insulin therapy from the time of diagnosis for at least 12 months
At least 4 years of age and less than 17 years
Females must have met one of the following criteria:
- Of childbearing potential but agreed to use an accepted contraceptive regimen as described in the study procedure manual throughout the entire duration of the study (from screening until study completion)
- Of non-childbearing potential, defined as a female who had a hysterectomy or tubal ligation, was clinically considered infertile or had not yet reached menarche
In good general health with no conditions that could have influenced the outcome of the trial, and in the judgment of the Investigator was a good candidate for the study based on review of available medical history, physical examination and clinical laboratory evaluations
Willingness to adhere to the study requirements

Exclusion Criteria:

An individual was not eligible if any of the following exclusion criteria were present:

Females who were pregnant according to a positive urine pregnancy test, actively attempting to get pregnant, or were lactating
History of hypersensitivity to glucagon or any related products or 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 have interfered with the absorption, distribution, metabolism or excretion of drugs or could potentiate or predispose to undesired effects
History of pheochromocytoma (i.e. adrenal gland tumor) or insulinoma
History of an episode of severe hypoglycemia (as defined by an episode that required third party assistance for treatment) in the 1 month prior to enrolling in the study
Use of daily systemic beta-blocker, indomethacin, warfarin or anticholinergic drugs
History of epilepsy or seizure disorder
Use of an Investigational Product in another clinical trial within the past 30 days
Blood donation in 3 months prior to first glucagon dosing

Sites / Locations

Barbara Davis Center for Diabetes
Yale University
University of Florida
Nemours Children's Clinic
Riley Hospital for Children Indiana University Health
University of Minnesota
UPA Buffalo

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Nasal Glucagon (NG)

Intramuscular (IM) Glucagon

Arm Description

Nasal glucagon (NG) doses of 2.0 mg and 3.0 mg for participants 4 to less than 12 years of age and 3.0 mg for those 12 to less than 17 years of age were administered in a nostril with a prefilled delivery device that delivered a single dose upon activation.

Participants who weighed at least 25 kilograms (kg)/55 pounds (lbs) were dosed 1 mg of IM glucagon; participants who weighed less than 25 kg/55 lbs, IM glucagon dosed with 0.5 mg

Outcomes

Primary Outcome Measures

Maximum Change From Baseline Concentration (Cmax) of Glucagon

Time to Maximum Concentration (Tmax) of Baseline Adjusted Glucagon

Area Under the Curve (AUC0-1.5) of Baseline Adjusted Glucagon

Maximum Concentration (Cmax) of Baseline-Adjusted Glucose

Time to Maximum Concentration (Tmax) of Baseline-Adjusted Glucose

Area Under the Effect Concentration Time Curve (AUEC0-1.5) of Baseline-Adjusted Glucose From Time Zero up to 90 Minutes

Secondary Outcome Measures

Nasal and Non-nasal Effects/Symptoms

Symptoms of runny nose, nasal congestion and/or itching, sneezing, watery and/or itchy eyes, redness of eyes, and itching of ears and/or throat were assessed prior to administering glucagon and at 15, 30, 60 and 90 minutes following administration of glucagon. This was done via the "Nasal Non-nasal Score Questionnaire". Each of the 9 symptoms is assigned an integer value from 0 to 3; higher values indicate more severe symptoms (a score of 0 indicates no symptoms). The reported results indicate the cohort median out of a possible maximum value of 27 (summing all 9 questions for each participant and reporting the median/IQR across participants).

Number of Participants Achieving at Least a 25 mg/dL Rise in Blood Glucose Above Nadir Level Within 30 Minutes

Time to Achieving ≥25 mg/dL Rise in Plasma Glucose Above Nadir Level Within 30 Minutes

Time (in minutes) when all participants experienced a rise in glucose >=25mg/dL. This is an absolute number and is not a calculated statistic. There is no distribution per cohort.

Full Information

NCT ID

NCT01997411

First Posted

November 22, 2013

Last Updated

August 1, 2018

Sponsor

Eli Lilly and Company

Collaborators

Jaeb Center for Health Research, Locemia Solutions ULC

1. Study Identification

Unique Protocol Identification Number

NCT01997411

Brief Title

Assessment of Intranasal Glucagon in Children and Adolescents With Type 1 Diabetes

Official Title

Assessment of Intranasal Glucagon in Children and Adolescents With Type 1 Diabetes

Study Type

Interventional

2. Study Status

Record Verification Date

August 2018

Overall Recruitment Status

Completed

Study Start Date

November 2013 (undefined)

Primary Completion Date

January 2015 (Actual)

Study Completion Date

January 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

Collaborators

Jaeb Center for Health Research, Locemia Solutions ULC

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study was to assess how glucagon administered nasally, using a nasal dosing delivery device, works in children and adolescents compared with commercially-available glucagon given by injection. In addition, the safety and tolerability of glucagon given nasally was evaluated.

Detailed Description

This study was conducted to permit determination of appropriate dose level(s) for pediatric use based on the safety observations and results of glucagon and glucose assays. Each participant 12 to less than 17 years of age underwent two visits in random order and received glucagon nasal powder once and commercially available glucagon (GlucaGen, Novo Nordisk) by intramuscular (IM) injection once. Participants 4 to less than 12 years were randomly assigned to have either 1 visit with commercially available glucagon (GlucaGen, Novo Nordisk) by IM injection OR to have 2 visits with a 2.0 milligram (mg) dose of glucagon nasal powder administered during one visit and a 3.0 mg dose of glucagon nasal powder administered during the other visit. For those randomized to complete two research dosing visits, the dose of glucagon nasal powder given during each visit was masked to the participant and study personnel. Glucagon was administered after glucose was lowered to <80 mg/dL using insulin if necessary on the dosing day. Participants were treated with either glucagon given nasally (either 2.0 mg or 3.0 mg for participants 4 to less than 12 years of age or 3.0 mg for those 12 to less than 17 years of age) or by intramuscular (IM) injection (1 mg for those 55 pounds [lbs] or more and 0.5 mg for those weighing less than 55 lbs) in the quadriceps muscle of the leg. Blood glucose levels and adverse events were carefully monitored for 90 minutes post-dosing. After a wash-out period of 7 days or more, participants 12 to less than 17 years of age returned to the clinic and the procedure was repeated with each participant crossed over to the other treatment. Participants 4 to less than 12 years assigned to have 2 dosing visits returned to clinic for repeated procedures and received alternate dose of nasal glucagon (NG). Participants 4 to less than 12 years assigned to a single dosing visit did not return for a second dosing visit.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes Mellitus, Type 1

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

IM and NG arms are open labeled. NG cohorts, 2mg and 3mg, are quadruple blinded.

Allocation

Randomized

Enrollment

48 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Nasal Glucagon (NG)

Arm Type

Experimental

Arm Description

Arm Title

Intramuscular (IM) Glucagon

Arm Type

Active Comparator

Arm Description

Participants who weighed at least 25 kilograms (kg)/55 pounds (lbs) were dosed 1 mg of IM glucagon; participants who weighed less than 25 kg/55 lbs, IM glucagon dosed with 0.5 mg

Intervention Type

Drug

Intervention Name(s)

Nasal Glucagon

Other Intervention Name(s)

AMG504-1, LY900018

Intervention Type

Drug

Intervention Name(s)

Intramuscular Glucagon

Other Intervention Name(s)

GlucaGen HypoKit

Primary Outcome Measure Information:

Title

Maximum Change From Baseline Concentration (Cmax) of Glucagon

Time Frame