Effectiveness and Safety of Intranasal Glucagon for Treatment of Hypoglycemia in Adults
|Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2||Drug: Intranasal Glucagon Drug: Intramuscular Glucagon||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Efficacy and Safety of Intranasal Glucagon for Treatment of Insulin Induced Hypoglycemia in Adults With Diabetes|
- Increase in Plasma Glucose Level to >=70mg/dL or an Increase of >=20mg/dL [ Time Frame: within 30 minutes after receiving glucagon ]Increase in blood glucose to >=70 mg/dL or an increase of >=20 mg/dL within 30 minutes after receiving glucagon, without receiving additional actions to increase the blood glucose level such as oral or intravenous glucose or additional glucagon.
- Nasal and Non-nasal Effects/Symptoms [ Time Frame: 15 to 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 will be assessed at 15, 30, 60 and 90 minutes following administration of glucagon.
- Recovery From Symptoms of Hypoglycemia [ Time Frame: plasma glucose <75 mg/dl to 60 minutes following administration of glucagon ]Recovery from clinical symptoms of hypoglycemia if present as documented using the hypoglycemia symptoms questionnaire which is completed when the plasma glucose reaches <75 mg/dL and at 15, 30, 45 and 60 minutes following administration of glucagon.
- Time From Glucagon Administration to Return of Plasma Glucose to >/=70 mg/dL [ 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 glucagon administration ]
- 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 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 ]
- 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 ]
|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 Glucagon
At one visit, a glucagon dose of 3 mg (equivalent to 30 mg of AMG 504-1 dry powder) will be administered in a nostril with a prefilled delivery device that delivers a single dose upon activation.
Drug: Intranasal Glucagon
Other Name: AMG504-1
Active Comparator: Intramuscular Glucagon
At a separate visit, 1 mg of commercially available recombinant human glucagon United States Pharmacopeia (USP) will be constituted in the provided prefilled disposable syringe containing 1 mL of diluting solution for injection into the deltoid muscle of the non-dominant arm.
Drug: Intramuscular Glucagon
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.
The procedure to evaluate the efficacy of AMG504-1 consists essentially of inducing hypoglycemia by an intravenous (IV) infusion of regular insulin diluted in normal saline. The insulin infusion will be used to decrease the glucose to a target <50 mg/dL. The insulin infusion will be stopped once the plasma glucose is <60 mg/dL. Five minutes after stopping the insulin infusion, participants will be treated with either a 3 mg glucagon dose intranasally or 1 mg of glucagon administered by intramuscular (IM) injection in the deltoid muscle of the non-dominant arm. During the 5-minute period after the insulin infusion has stopped, the glucose level is expected to continue to decrease an additional 15-20 mg/dL.
It is believed that a nadir of <50 mg/dL will be low enough to generate clinical symptoms in most participants yet high enough to avoid impairment of consciousness. Blood glucose levels and adverse events will be carefully monitored for 90 minutes post-dosing. After a wash-out period of 7 days or more, participants will return to the clinic and the procedure repeated with each participant crossed over to the other treatment. As such, each participant will undergo two episodes of insulin-induced hypoglycemia in random order and receive AMG504-1 during one episode and commercially available glucagon (GlucaGen, Novo Nordisk) by IM injection during the other episode.
Please refer to this study by its ClinicalTrials.gov identifier: 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|
|Principal Investigator:||Katrina J Ruedy, MSPH||Jaeb Center for Health Research|