Efficacy and Safety of Nasal Glucagon for Treatment of Hypoglycemia in Adults
|ClinicalTrials.gov Identifier: NCT01994746|
Recruitment Status : Completed
First Posted : November 26, 2013
Results First Posted : October 10, 2016
Last Update Posted : September 23, 2019
|Condition or disease||Intervention/treatment||Phase|
|Diabetes Mellitus, Type 1||Drug: Nasal Glucagon Drug: Intramuscular Glucagon||Phase 3|
Each glucagon dosing visit was conducted after an overnight fast of at least 8 h with a starting plasma glucose >= 90 mg/dL. Hypoglycemia was induced by an intravenous (IV) infusion of regular insulin diluted in normal saline during the clinic visit. Five minutes after stopping the insulin infusion (once the plasma glucose was <60 mg/dL), participants were treated with either a 3 mg glucagon dose nasally or 1 mg of glucagon administered by intramuscular (IM) injection.
After a wash-out period of 7 days or more, participants returned to the clinic and the procedure repeated with each participant crossed over to the other treatment. As such, each participant underwent two episodes of insulin-induced hypoglycemia in random order and received glucagon nasal powder during one episode and commercially available glucagon (GlucaGen, Novo Nordisk) by IM injection during the other episode.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||77 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||None (Open Label)|
|Official Title:||Efficacy and Safety of Nasal Glucagon for Treatment of Insulin Induced Hypoglycemia in Adults With Diabetes|
|Study Start Date :||November 2013|
|Actual Primary Completion Date :||January 2015|
|Actual Study Completion Date :||January 2015|
Experimental: Nasal Glucagon
At one visit, a glucagon dose of 3 mg was administered in a nostril with a prefilled delivery device that delivers a single dose upon activation.
Drug: Nasal Glucagon
Active Comparator: Intramuscular Glucagon
At a separate visit, 1 mg of glucagon was administered into the deltoid muscle of the non-dominant arm (intramuscular [IM]).
Drug: Intramuscular Glucagon
Other Name: GlucaGen HypoKit
- Increase in Plasma Glucose Level to >=70mg/dL or an Increase of >=20mg/dL From Glucose Nadir [ Time Frame: Within 30 minutes after receiving glucagon at both dosing visits (glucose was measured at pre-dose; 5, 10, 15, 20, 25, and 30 minutes following glucagon administration) ]Increase in blood glucose to ≥70 mg/dL or an increase of ≥20 mg/dL from glucose nadir within 30 minutes after receiving study glucagon, without receiving additional actions to increase the blood glucose level defines treatment success. Due to the residual activity of circulating insulin, glucose nadir was defined as the minimum glucose measurement at the time of, or within 10 minutes following glucagon administration.
- Nasal and Non-nasal Effects/Symptoms [ Time Frame: Pre-dose; 15, 30, 60, and 90 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. 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 subject and reporting the median/IQR across participants).
- Recovery From Symptoms of Hypoglycemia [ Time Frame: Pre-dose;15, 30, 45 and 60 minutes following administration of glucagon ]Recovery from hypoglycemia symptoms were assessed using the Edinburgh Hypoglycemia Scale. The Edinburgh Hypoglycemia Symptom Scale measures the intensity of 15 commonly experienced hypoglycemic symptoms on a 7-point Likert scale (1 = not present, 7 = very intense). The higher the score, the more intense the hypoglycemia symptoms. The sum of each symptom score would yield a range of 15 to 105 (i.e., 15 x 7 =105). The total score was calculated as the sum of each symptom score minus 15, and summarized at each time point by treatment group.
- Time From Glucagon Administration to Blood Glucose >/=70 mg/dL or an Increase ≥20 mg/dL in Blood Glucose From Nadir [ Time Frame: Pre-dose; 5, 10, 15, 20, 25, and 30 minutes following glucagon administration ]The mean time from glucagon administration to blood glucose >/=70 mg/dL or an increase ≥20 mg/dL in blood glucose from nadir.
- Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Baseline-Adjusted Glucagon [ Time Frame: Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration ]
- Maximum Change From Baseline Concentration (Cmax) of Glucagon [ Time Frame: Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration ]
- Time to Maximum Change From Baseline Concentration (Tmax) of Glucagon [ Time Frame: Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration ]
- Area Under the Effect Concentration Time Curve (AUEC0-1.5) of Baseline-Adjusted Glucose From Time Zero up to 90 Minutes [ Time Frame: Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration ]
- Maximum Change From Baseline Concentration (Cmax) of Glucose [ Time Frame: Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration ]
- Time to Maximum Change From Baseline Concentration (Tmax) of Glucose [ Time Frame: Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01994746
|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|
|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|
|United States, Oregon|
|Oregon Health and Science University|
|Portland, Oregon, United States, 97239|
|United States, Pennsylvania|
|University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Study Director:||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)||Eli Lilly and Company|