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Efficacy and Safety of Nasal Glucagon for Treatment of Hypoglycemia in Adults

Primary Purpose

Diabetes Mellitus, Type 1

Status

Completed

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Nasal Glucagon

Intramuscular Glucagon

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 1

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Nasal Glucagon

Intramuscular Glucagon

Arm Description

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.

At a separate visit, 1 mg of glucagon was administered into the deltoid muscle of the non-dominant arm (intramuscular [IM]).

Outcomes

Primary Outcome Measures

Increase in Plasma Glucose Level to >=70mg/dL or an Increase of >=20mg/dL From Glucose Nadir

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.

Secondary Outcome Measures

Nasal and Non-nasal Effects/Symptoms

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

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

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

Maximum Change From Baseline Concentration (Cmax) of Glucagon

Time to Maximum Change From Baseline Concentration (Tmax) of Glucagon

Area Under the Effect Concentration Time Curve (AUEC0-1.5) of Baseline-Adjusted Glucose From Time Zero up to 90 Minutes

Maximum Change From Baseline Concentration (Cmax) of Glucose

Time to Maximum Change From Baseline Concentration (Tmax) of Glucose

Full Information

NCT ID

NCT01994746

First Posted

November 20, 2013

Last Updated

September 5, 2019

Sponsor

Eli Lilly and Company

Collaborators

T1D Exchange Clinic Network Coordinating Center, Locemia Solutions ULC

1. Study Identification

Unique Protocol Identification Number

NCT01994746

Brief Title

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

2. Study Status

Record Verification Date

September 2019

Overall Recruitment Status

Completed

Study Start Date

November 2013 (undefined)

Primary Completion Date

January 2015 (Actual)

Study Completion Date

January 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

Collaborators

T1D Exchange Clinic Network Coordinating Center, Locemia Solutions ULC

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes Mellitus, Type 1

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

77 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Nasal Glucagon

Arm Type

Experimental

Arm Description

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.

Arm Title

Intramuscular Glucagon

Arm Type

Active Comparator

Arm Description

At a separate visit, 1 mg of glucagon was administered into the deltoid muscle of the non-dominant arm (intramuscular [IM]).

Intervention Type

Drug

Intervention Name(s)

Nasal Glucagon

Other Intervention Name(s)

AMG504-1, LY900018

Intervention Type

Drug

Intervention Name(s)

Intramuscular Glucagon

Other Intervention Name(s)

GlucaGen HypoKit

Primary Outcome Measure Information:

Title

Increase in Plasma Glucose Level to >=70mg/dL or an Increase of >=20mg/dL From Glucose Nadir

Description

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)

Secondary Outcome Measure Information:

Title

Nasal and Non-nasal Effects/Symptoms

Description

Time Frame

Pre-dose; 15, 30, 60, and 90 post glucagon administration

Title

Recovery From Symptoms of Hypoglycemia

Description

Time Frame

Pre-dose;15, 30, 45 and 60 minutes following administration of glucagon

Title

Time From Glucagon Administration to Blood Glucose >/=70 mg/dL or an Increase ≥20 mg/dL in Blood Glucose From Nadir

Description

The mean 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

Title

Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Baseline-Adjusted Glucagon

Time Frame