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

NCT ID: NCT01997411

Last Updated: 2018-08-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-30
• Study Completion Date: 2015-01-31

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.

Conditions

Diabetes Mellitus, Type 1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Nasal Glucagon (NG)

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.

Group Type: EXPERIMENTAL

Nasal Glucagon

Intervention Type: DRUG

Intramuscular (IM) Glucagon

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

Group Type: ACTIVE_COMPARATOR

Intramuscular Glucagon

Intervention Type: DRUG

Interventions

Nasal Glucagon

Intervention Type: DRUG

Intramuscular Glucagon

Intervention Type: DRUG

Other Intervention Names

AMG504-1; LY900018; GlucaGen HypoKit

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jaeb Center for Health Research

OTHER

Sponsor Role: collaborator

Locemia Solutions ULC

INDUSTRY

Sponsor Role: collaborator

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

Barbara Davis Center for Diabetes

Aurora, Colorado, United States

Yale University

New Haven, Connecticut, United States

University of Florida

Gainesville, Florida, United States

Nemours Children's Clinic

Jacksonville, Florida, United States

Riley Hospital for Children Indiana University Health

Indianapolis, Indiana, United States

University of Minnesota

Minneapolis, Minnesota, United States

UPA Buffalo

Buffalo, New York, United States

Countries

United States

References

Sherr JL, Ruedy KJ, Foster NC, Piche CA, Dulude H, Rickels MR, Tamborlane WV, Bethin KE, DiMeglio LA, Fox LA, Wadwa RP, Schatz DA, Nathan BM, Marcovina SM, Rampakakis E, Meng L, Beck RW; T1D Exchange Intranasal Glucagon Investigators. Glucagon Nasal Powder: A Promising Alternative to Intramuscular Glucagon in Youth With Type 1 Diabetes. Diabetes Care. 2016 Apr;39(4):555-62. doi: 10.2337/dc15-1606. Epub 2016 Feb 16.

Reference Type: DERIVED

PMID: 26884472 (View on PubMed)

Other Identifiers

I8R-MC-IGBB

Identifier Type: OTHER

Identifier Source: secondary_id

INGluc002

Identifier Type: OTHER

Identifier Source: secondary_id

AMG103

Identifier Type: OTHER

Identifier Source: secondary_id

16418

Identifier Type: -

Identifier Source: org_study_id