Clinical trial NCT01994746: Efficacy and Safety of Nasal Glucagon for Treatment of Hypoglycemia in Adults
Official title: Efficacy and Safety of Nasal Glucagon for Treatment of Insulin Induced Hypoglycemia in Adults With Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 1
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: T1D Exchange Clinic Network Coordinating Center
name: Locemia Solutions ULC
First posted: 2013-11-26
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and safety of 3 milligrams (mg) glucagon (glucagon nasal powder) administered nasally compared with commercially available glucagon given by intramuscular injection.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

To be eligible, the following inclusion criteria must be met:

* Clinical diagnosis of either type 1 diabetes receiving daily insulin since the time of diagnosis for at least 2 years or type 2 diabetes receiving multiple daily insulin doses for at least 2 years
* At least 18.0 years of age and less than 65.0 years
* Body mass index (BMI) greater than or equal to 20.0 and below or equal to 35.0 kilograms per meter squared (kg/m²)
* Weighs at least 50 kg (110 pounds)
* Females must meet one of the following criteria:

  * Of childbearing potential but agree to use an accepted contraceptive regimen as described in the study procedure manual throughout the entire duration of the study (from the screening until study completion)
  * Of non-childbearing potential, defined as a female who has had a hysterectomy or tubal ligation, is clinically considered infertile or is in a menopausal state (at least 1 year without menses)
* In good general health with no conditions that could influence the outcome of the trial, and in the judgment of the Investigator is 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 is not eligible if any of the following exclusion criteria are present:

* Females who are pregnant according to a positive urine pregnancy test, actively attempting to get pregnant, or are 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 interfere 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
* Regularly consumes 3 or more alcoholic beverages per day
* Use of an Investigational Product in another clinical trial within the past 30 days
* Donated 225 milliliters (mL) or more of blood in the previous 8 weeks before the first glucagon dosing

Primary outcomes:
measure: Increase in Plasma Glucose Level to >=70mg/dL or an Increase of >=20mg/dL From Glucose Nadir
timeFrame: 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)
Secondary outcomes:
measure: Nasal and Non-nasal Effects/Symptoms
timeFrame: Pre-dose; 15, 30, 60, and 90 post glucagon administration
measure: Recovery From Symptoms of Hypoglycemia
timeFrame: Pre-dose;15, 30, 45 and 60 minutes following administration of glucagon
measure: Time From Glucagon Administration to Blood Glucose >/=70 mg/dL or an Increase ≥20 mg/dL in Blood Glucose From Nadir
timeFrame: Pre-dose; 5, 10, 15, 20, 25, and 30 minutes following glucagon administration
measure: Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Baseline-Adjusted Glucagon
timeFrame: Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration
measure: Maximum Change From Baseline Concentration (Cmax) of Glucagon
timeFrame: Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration
measure: Time to Maximum Change From Baseline Concentration (Tmax) of Glucagon
timeFrame: Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 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, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration
measure: Maximum Change From Baseline Concentration (Cmax) of Glucose
timeFrame: Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration
measure: Time to Maximum Change From Baseline Concentration (Tmax) of Glucose
timeFrame: Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration
Other outcomes:
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: 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
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
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: Rickels MR, Ruedy KJ, Foster NC, Piche CA, Dulude H, Sherr JL, Tamborlane WV, Bethin KE, DiMeglio LA, Wadwa RP, Ahmann AJ, Haller MJ, Nathan BM, Marcovina SM, Rampakakis E, Meng L, Beck RW; T1D Exchange Intranasal Glucagon Investigators. Intranasal Glucagon for Treatment of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes: A Randomized Crossover Noninferiority Study. Diabetes Care. 2016 Feb;39(2):264-70. doi: 10.2337/dc15-1498. Epub 2015 Dec 17.