Assessment of Intranasal Glucagon in Children and Adolescents With Type 1 Diabetes
|Diabetes Mellitus, Type 1||Drug: Intranasal Glucagon Drug: Glucagon||Phase 2 Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||Assessment of Intranasal Glucagon in Children and Adolescents With Type 1 Diabetes|
- Percentage of Participants With >= 25 mg/dL Rise in Plasma Glucose [ Time Frame: 0 to 20 minutes following administration of glucagon ]
- Maximum Observed Concentration (Cmax) of Glucagon [ Time Frame: 0 to 90 minutes following glucagon administration ]
- Time to Maximum Concentration (Tmax) of Glucagon [ Time Frame: 0 to 90 minutes following glucagon administration ]
- Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Glucagon [ Time Frame: 0 to 90 minutes following administration of glucagon ]
- Nasal and Non-nasal Effects/Symptoms [ Time Frame: Timepoints of 15 minutes, 30 minutes, 60 minutes, and 90 minutes post 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 is 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 subject and reporting the median/IQR across participants).
- Maximum Concentration (Cmax) of Glucose [ Time Frame: 0 to 90 minutes following glucagon administration ]
- Time to Maximum Concentration (Tmax) of Glucose [ Time Frame: 0 to 90 minutes following glucagon administration ]
- Area Under the Effect Concentration Time Curve (AUEC0-1.5) of Glucose From Time Zero up to 90 Minutes [ Time Frame: 0 to 90 minutes following glucagon administration ]
- The Proportion and 99% Confidence Interval of Participants Achieving at Least a 25 mg/dl Rise in Blood Glucose Above Basal Level [ Time Frame: 0 to 90 minutes following glucagon administration ]
- Time to Achieving ≥25 mg/dl Rise in Plasma Glucose Above Basal Level [ Time Frame: 0 to 90 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.
|Study Start Date:||November 2013|
|Study Completion Date:||January 2015|
|Primary Completion Date:||January 2015 (Final data collection date for primary outcome measure)|
Experimental: Intranasal (IN) Glucagon
Glucagon doses of 2.0 mg and 3.0 mg for participants 4.0 to less than 12.0 years of age and 3.0 mg for those 12.0 to less than 17.0 years of age (equivalent to 20 mg or 30 mg of AMG504-1 dry powder, respectively) were administered in a nostril with a prefilled delivery device that delivered a single dose upon activation.
Drug: Intranasal Glucagon
Other Name: AMG504-1
Active Comparator: Intramuscular (IM) Glucagon
Participants who weigh at least 25 kg (55) lbs were dosed 1 mg of recombinant human glucagon United States Pharmacopeia (USP) which was constituted in the commercially provided prefilled disposable syringe containing 1 mL of diluting solution. For participants who weigh less than 25 kg, the dose was 0.5 mg constituted in 1 mL of diluting solution.
Other Name: GlucaGen HypoKit
Glucagon, the treatment of choice for severe hypoglycemia outside of the hospital setting, is currently available only as a powder that must be mixed with a diluent immediately prior to administration by injection. Although this is a very simple procedure for insulin-using individuals, subjects experiencing severe hypoglycemia cannot inject themselves with glucagon because of the disabling effects of severe neuroglycopenia. For any non-medical person who is confronted with an emergency situation in which a patient with diabetes is in a hypoglycemic coma or suffering hypoglycemia-related convulsions, reconstitution and injection of the current injectable glucagon is a complex and daunting procedure.
When used at the recommended dose of 1 mg by injection, glucagon often causes a substantial, although transient, hyperglycemia that is often accompanied by nausea and vomiting. The data generated to date with AMG504-1 suggest the resulting glucagon pharmacokinetics (PK), although less than that observed with injected glucagon, results in a therapeutic blood glucose increment with a very low incidence of gastrointestinal adverse effects.
Caregivers of children and adolescents with type 1 diabetes are called upon to treat episodes of severe hypoglycemia and may want to use AMG504-1. 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 12.0 to less than 17.0 years of age underwent two visits in random order and received AMG504-1 during one visit and commercially available glucagon (GlucaGen, Novo Nordisk) by IM injection during the other visit. Participants 4.0 to less than 12.0 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 mg dose of AMG504-1 administered during one visit and a 3.0 mg dose of AMG504-1 administered during the other visit. For those randomized to complete two research dosing visits, the dose of intranasal glucagon given during each visit was masked to the participant and study personnel.
Each dosing visit consisted of reducing the plasma glucose level to about 80 mg/dL by increasing the basal insulin infusion rate on the insulin pump or by an intravenous (IV) infusion of regular insulin diluted in normal saline. The insulin infusion was stopped once the plasma glucose was <80 mg/dL. Five minutes after stopping the insulin infusion, participants were treated with either glucagon given intranasally (either 2.0 mg or 3.0 mg for participants 4.0 to less than 12.0 years of age or 3.0 mg for those 12.0 to less than 17.0 years of age) or by intramuscular (IM) injection (1 mg constituted in 1 mL of diluting solution for those 55 lbs or more and 0.5 mg constituted in 1 mL of diluting solution for those who weigh 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 12.0 to less than 17.0 years of age returned to the clinic and the procedure repeated with each participant crossed over to the other treatment. Participants 4.0 to less than 12.0 years assigned to have 2 dosing visits returned to clinic and repeated the procedure with a different dose of intranasal glucagon given. Participants 4.0 to less than 12.0 years assigned to a single dosing visit did not return for a second dosing visit.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01997411
|United States, Colorado|
|Barbara Davis Center for Diabetes|
|Aurora, Colorado, United States, 80045|
|United States, Connecticut|
|New Haven, Connecticut, United States, 06520|
|United States, Florida|
|University of Florida|
|Gainesville, Florida, United States, 32605|
|Nemours Children's Clinic|
|Jacksonville, Florida, United States, 32207|
|United States, Indiana|
|Riley Hospital for Children Indiana University Health|
|Indianapolis, Indiana, United States, 46202|
|United States, Minnesota|
|University of Minnesota|
|Minneapolis, Minnesota, United States, 55454|
|United States, New York|
|Buffalo, New York, United States, 14222|
|Principal Investigator:||Katrina J Ruedy, MSPH||Jaeb Center for Health Research|