Trial · Interventional

CompletedPhase 3Results postedRegistry data

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

NCTNCT01994746Other id16422Other idINGluc001Other idI8R-MC-IGBCOther idAMG106

Open at ClinicalTrials.govAsk about this trial

Overview

Status: Completed
Phase: Phase 3
Enrollment: 77 participants (actual)
Sponsor: Eli Lilly and Company · Industry
Design: Randomized · Open label (no masking)
Countries: 1 country
United States
Start: Nov 2013
Primary completion: Jan 2015
Completion: Jan 2015
First posted: 26 Nov 2013 (estimated)
Last update posted: 23 Sept 2019
Conditions: Diabetes Mellitus, Type 1

Timeline

1 trial · 1 completed · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

2013201420152016

Ph 3
Efficacy and Safety of Nasal Glucagon for Treatment of Hypoglycemia in Adults
NCT01994746
Nov 2013 to Jan 2015

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

Nasal GlucagonDrug
Intramuscular GlucagonDrug

Arms2

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

Primary outcomes1

Outcomes the sponsor listed as primary.

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)
Registry description
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 outcomes(9)

Nasal and Non-nasal Effects/Symptoms
Time frame · Pre-dose; 15, 30, 60, and 90 post glucagon administration
Registry description
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
Registry description
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
Registry description
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

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

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

Group	Value (percentage of participants)
Nasal Glucagon (NG)	98.7
Intramuscular (IM) Glucagon	100

Secondary and other outcome results(7)

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

Nasal and Non-nasal Effects/Symptoms

Group	Value (units on a scale)
Nasal Glucagon (NG)	0.00
Intramuscular (IM) Glucagon	0.00

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

Recovery From Symptoms of Hypoglycemia

Group	Value (units on a scale)	Spread
Nasal Glucagon (NG)	8.0	7.7
Intramuscular (IM) Glucagon	7.8	7.1

Secondary outcomeNumber· Pre-dose; 5, 10, 15, 20, 25, and 30 minutes following glucagon administration

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

Group	Value (minutes)
Nasal Glucagon (NG)	16.2
Intramuscular (IM) Glucagon	12.2

Secondary outcomeMean· Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration

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

Group	Value (hourpicograms per milliliter (hrpg/mL))	Spread
Nasal Glucagon (NG)	1882.48	1216.27
Intramuscular (IM) Glucagon	2521.87	971.07

Secondary outcomeMean· 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

Group	Value (picograms per milliliter (pg/mL))	Spread
Nasal Glucagon (NG)	3025.37	1981.62
Intramuscular (IM) Glucagon	3553.43	1746.66

Secondary outcomeMedian· 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

Group	Value (hours)
Nasal Glucagon (NG)	0.33
Intramuscular (IM) Glucagon	0.25

Secondary outcomeMean· 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

Group	Value (hr*mg/dL)	Spread
Nasal Glucagon (NG)	106.39	42.60
Intramuscular (IM) Glucagon	124.47	38.95

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
Nasal Glucagon (NG)At one visit, 3 mg of NG.	–	0 / 77	44 / 77
Intramuscular (IM) GlucagonAt a separate visit, 1 mg of IM glucagon.	–	0 / 77	35 / 76

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies2

Studies that cite this trial.

Studies with results

2 studies on this page

PubMed tag: none · 2024

10 results

Nasal Glucagon Reverses Insulin-induced Hypoglycemia With Less Rebound Hyperglycemia: Pooled Analysis of Clinical Trials.

Seaquist et al. 2024Journal of the Endocrine Societycited by 2

PMID 38444629PMC10913376DOI 10.1210/jendso/bvae034PUB-38444629

Free to read · publisher termsCC BY-NC-ND10 results

Read at source See results (10)

Indexing hint: Randomized controlled trial · 2016

4 results

Intranasal Glucagon for Treatment of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes: A Randomized Crossover Noninferiority Study.

Rickels et al. 2016Diabetes carecited by 85

PMID 26681725PMC4722945DOI 10.2337/dc15-1498PUB-26681725

Rights unknown4 results

Source link See results (4)

Eligibility

Who could join, as posted.

Sex: All
Age: from 18 Years up to 64 Years
Healthy volunteers: Not accepted

Inclusion and exclusion criteria, as posted

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

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