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

Status

Completed

Phases

Phase 2Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01997411

Enrollment

Registered

2013-11-28

Start date

2013-11-30

Completion date

2015-01-31

Last updated

2018-08-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes Mellitus, Type 1

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.

Interventions

DRUGNasal Glucagon

DRUGIntramuscular Glucagon

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Masking description

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

Eligibility

Sex/Gender

ALL

Age

4 Years to 16 Years

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

Design outcomes

Primary

Measure	Time frame
Area Under the Effect Concentration Time Curve (AUEC0-1.5) of Baseline-Adjusted Glucose From Time Zero up to 90 Minutes	Pre-dose; 5, 10, 15, 20, 30, 40, 60 and 90 minutes following glucagon administration
Time to Maximum Concentration (Tmax) of Baseline Adjusted Glucagon	Pre-dose; 5, 10, 15, 20, 30, 40, 60 and 90 minutes following glucagon administration
Area Under the Curve (AUC0-1.5) of Baseline Adjusted Glucagon	Pre-dose; 5, 10, 15, 20, 30, 40, 60 and 90 minutes following glucagon administration
Maximum Concentration (Cmax) of Baseline-Adjusted Glucose	Pre-dose; 5, 10, 15, 20, 30, 40, 60 and 90 minutes following glucagon administration
Time to Maximum Concentration (Tmax) of Baseline-Adjusted Glucose	Pre-dose; 5, 10, 15, 20, 30, 40, 60 and 90 minutes following glucagon administration
Maximum Change From Baseline Concentration (Cmax) of Glucagon	Pre-dose; 5, 10, 15, 20, 30, 40, 60 and 90 minutes following glucagon administration

Secondary

Measure	Time frame	Description
Nasal and Non-nasal Effects/Symptoms	Pre-dose;15, 30, 60 and 90 minutes following glucagon administration	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	Pre-dose; 5, 10, 15, 20, and 30 minutes following glucagon administration	—
Time to Achieving ≥25 mg/dL Rise in Plasma Glucose Above Nadir Level Within 30 Minutes	Pre-dose; 5, 10, 15, 20, and 30 minutes following glucagon administration	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.

Other

Measure	Time frame
Percentage of Participants With >= 25 mg/dL Rise in Plasma Glucose Within 30 Minutes	Pre-dose; 5, 10,15, 20, and 30 minutes following glucagon administration

Countries

United States

Participant flow

Participants by arm

Arm	Count
4 to <8 Years Old IM Glucagon Cohort Participants who were 4 to \< 8 years old at the time of enrollment into the study randomized to receive only the intramuscular glucagon at one visit.	6
4 to <8 Years Old NG Cohort Participants who were 4 to \< 8 years old at the time of enrollment into the study randomized to receive 2.0 or 3.0 mg of nasal glucagon at two separate visits. Order of these visits was randomized.	12
8 to <12 Years Old IM Glucagon Cohort Participants who were 8 to \< 12 years old at the time of enrollment into the study randomized to receive only the intramuscular glucagon at one visit.	6
8 to <12 Years Old NG Cohort Participants who were 8 to \< 12 years old at the time of enrollment into the study randomized to receive 2.0 or 3.0 mg of nasal glucagon at two separate visits. Order of these visits was randomized.	12
12 to <17 Years Old NG/IM Cohort Participants who were 12 to \< 17 years old at the time of enrollment into the study randomized to receive either intramuscular glucagon or nasal glucagon at two separate visits. Order of these visits was randomized.	12
Total	48

Baseline characteristics

Characteristic	4 to <8 Years Old IM Glucagon Cohort	4 to <8 Years Old NG Cohort	8 to <12 Years Old IM Glucagon Cohort	8 to <12 Years Old NG Cohort	12 to <17 Years Old NG/IM Cohort	Total
Age, Continuous	6.8 years	6.8 years	11.1 years	11.1 years	14.5 years	10.6 years
Duration of Diabetes	3.1 years	2.7 years	5.3 years	4.3 years	5.9 years	3.9 years
Local HbA1c	7.6 percent STANDARD_DEVIATION 0.5	8.3 percent STANDARD_DEVIATION 0.8	7.5 percent STANDARD_DEVIATION 1.1	8.1 percent STANDARD_DEVIATION 0.7	8.2 percent STANDARD_DEVIATION 1.5	8.0 percent STANDARD_DEVIATION 1
Region of Enrollment United States	6 Participants	12 Participants	6 Participants	12 Participants	12 Participants	48 Participants
Sex: Female, Male Female	0 Participants	3 Participants	3 Participants	5 Participants	5 Participants	16 Participants
Sex: Female, Male Male	6 Participants	9 Participants	3 Participants	7 Participants	7 Participants	32 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	5 / 6	6 / 12	5 / 12	6 / 6	5 / 11	6 / 12	7 / 12	9 / 12
serious Total, serious adverse events	1 / 6	0 / 12	0 / 12	0 / 6	0 / 11	0 / 12	0 / 12	0 / 12