Clinical trial NCT01997411: 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
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Diabetes Mellitus, Type 1
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: Jaeb Center for Health Research
name: Locemia Solutions ULC
First posted: 2013-11-28
Enrollment: 48
Sex: ALL
Minimum age (years): 4
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum Change From Baseline Concentration (Cmax) of Glucagon
timeFrame: Pre-dose; 5, 10, 15, 20, 30, 40, 60 and 90 minutes following glucagon administration
measure: Time to Maximum Concentration (Tmax) of Baseline Adjusted Glucagon
timeFrame: Pre-dose; 5, 10, 15, 20, 30, 40, 60 and 90 minutes following glucagon administration
measure: Area Under the Curve (AUC0-1.5) of Baseline Adjusted Glucagon
timeFrame: Pre-dose; 5, 10, 15, 20, 30, 40, 60 and 90 minutes following glucagon administration
measure: Maximum Concentration (Cmax) of Baseline-Adjusted Glucose
timeFrame: Pre-dose; 5, 10, 15, 20, 30, 40, 60 and 90 minutes following glucagon administration
measure: Time to Maximum Concentration (Tmax) of Baseline-Adjusted Glucose
timeFrame: Pre-dose; 5, 10, 15, 20, 30, 40, 60 and 90 minutes following glucagon administration
measure: Area Under the Effect Concentration Time Curve (AUEC0-1.5) of Baseline-Adjusted Glucose From Time Zero up to 90 Minutes
timeFrame: Pre-dose; 5, 10, 15, 20, 30, 40, 60 and 90 minutes following glucagon administration
Secondary outcomes:
measure: Nasal and Non-nasal Effects/Symptoms
timeFrame: Pre-dose;15, 30, 60 and 90 minutes following glucagon administration
measure: Number of Participants Achieving at Least a 25 mg/dL Rise in Blood Glucose Above Nadir Level Within 30 Minutes
timeFrame: Pre-dose; 5, 10, 15, 20, and 30 minutes following glucagon administration
measure: Time to Achieving ≥25 mg/dL Rise in Plasma Glucose Above Nadir Level Within 30 Minutes
timeFrame: Pre-dose; 5, 10, 15, 20, and 30 minutes following glucagon administration
Other outcomes:
measure: Percentage of Participants With >= 25 mg/dL Rise in Plasma Glucose Within 30 Minutes
timeFrame: Pre-dose; 5, 10,15, 20, and 30 minutes following glucagon administration
Locations:
city: Aurora
country: United States
facility: Barbara Davis Center for Diabetes
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Indianapolis
country: United States
facility: Riley Hospital for Children Indiana University Health
state: Indiana
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Buffalo
country: United States
facility: UPA Buffalo
state: New York
Study officials:
affiliation: Eli Lilly and Company
name: 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
References:
citation: 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.