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| ID | Type | Description | Link |
|---|---|---|---|
| INGluc001 | Other Identifier | Jaeb Center for Health Research | |
| I8R-MC-IGBC | Other Identifier | Eli Lilly and Company | |
| AMG106 | Other Identifier | Locemia |
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| Name | Class |
|---|---|
| T1D Exchange Clinic Network Coordinating Center | UNKNOWN |
| Locemia Solutions ULC | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Nasal Glucagon | Experimental | 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. |
|
| Intramuscular Glucagon | Active Comparator | At a separate visit, 1 mg of glucagon was administered into the deltoid muscle of the non-dominant arm (intramuscular [IM]). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nasal Glucagon | Drug |
|
| |
| Intramuscular Glucagon |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
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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:
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:
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| Name | Affiliation | Role |
|---|---|---|
| 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 | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Barbara Davis Center for Diabetes | Aurora | Colorado | 80045 | United States | ||
| Yale University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26681725 | Background | 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. | |
| 38444629 |
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Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
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77 Type 1 (T1D) and 6 Type 2 diabetes (T2D) participants were recruited. Results reported include T1D participants only since this was the pre-specified primary population.
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| ID | Title | Description |
|---|---|---|
| FG000 | NG 1st/IM Glucagon 2nd | At the first visit, 3 milligrams (mg) of nasal glucagon (NG). At the second visit, 1 mg of intramuscular (IM) glucagon. |
| FG001 | IM Glucagon 1st/NG 2nd | At the first visit, 1 mg of IM glucagon. At the second visit, 3 mg of NG glucagon. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Visit |
| ||||||||||||||||
| Second Visit |
|
Participants that received at least one does of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | At one visit, a nasal glucagon (NG) dose of 3 mg. At another visit, 1 mg intramuscular (IM) glucagon The order of the visits were randomized. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | All enrolled participants who completed both eligible Study/Dosing Visits. | Posted | Number | percentage of participants | 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) |
|
Through study completion, up to 48 days
Included all participants received at least one dose of glucagon.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Nasal Glucagon (NG) | At one visit, 3 mg of NG. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 800-545-5979 |
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| Drug |
|
|
| Pre-dose; 15, 30, 60, and 90 post glucagon administration |
| 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. | Pre-dose;15, 30, 45 and 60 minutes following administration of glucagon |
| 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. | Pre-dose; 5, 10, 15, 20, 25, and 30 minutes following glucagon administration |
| Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Baseline-Adjusted Glucagon | 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 | 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 | 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 | 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 | 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 | Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration |
| New Haven |
| Connecticut |
| 06520 |
| United States |
| University of Florida | Gainesville | Florida | 32605 | United States |
| Riley Hospital for Children Indiana University Health | Indianapolis | Indiana | 46202 | United States |
| University of Minnesota | Minneapolis | Minnesota | 55454 | United States |
| UPA Buffalo | Buffalo | New York | 14222 | United States |
| Oregon Health and Science University | Portland | Oregon | 97239 | United States |
| University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| Derived |
| Seaquist E, Gimenez M, Yan Y, Matsuhisa M, Kao CY, Wadwa RP, Nagai Y, Khunti K. Nasal Glucagon Reverses Insulin-induced Hypoglycemia With Less Rebound Hyperglycemia: Pooled Analysis of Clinical Trials. J Endocr Soc. 2024 Feb 26;8(4):bvae034. doi: 10.1210/jendso/bvae034. eCollection 2024 Feb 19. |
| COMPLETED |
|
| NOT COMPLETED |
|
| Participants |
| No |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants | No |
|
| Race (NIH/OMB) | Count of Participants | Participants | No |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | Intramuscular (IM) Glucagon | At a separate visit, 1 mg of IM glucagon. |
|
|
| Secondary | 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). | All enrolled T1D participants that completed the required dosing visits. Study dosing visits occur on Day 0 and then again after the washout period between Day 7 to Day 28. | Posted | Median | Inter-Quartile Range | units on a scale | Pre-dose; 15, 30, 60, and 90 post glucagon administration |
|
|
|
| Secondary | 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. | All enrolled participants who completed at least one post administration survey. | Posted | Mean | Standard Deviation | units on a scale | Pre-dose;15, 30, 45 and 60 minutes following administration of glucagon |
|
|
|
| Secondary | 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. | All enrolled participants that completed the required dosing visits with eligible glucose and glucagon levels. Study dosing visits occur on Day 0 and then again after the washout period between Day 7 to Day 28. | Posted | Number | minutes | Pre-dose; 5, 10, 15, 20, 25, and 30 minutes following glucagon administration |
|
|
|
| Secondary | Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Baseline-Adjusted Glucagon | All enrolled participants that completed the required dosing visits with available pharmacokinetics (PK) data. Study dosing visits occurred on Day 0 and then again after the washout period between Day 7 to Day 28. | Posted | Mean | Standard Deviation | hour*picograms per milliliter (hr*pg/mL) | Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration |
|
|
|
| Secondary | Maximum Change From Baseline Concentration (Cmax) of Glucagon | All enrolled participants that completed the required dosing visits with available pharmacokinetics (PK) data. Study dosing visits occurred on Day 0 and then again after the washout period between Day 7 to Day 28. | Posted | Mean | Standard Deviation | picograms per milliliter (pg/mL) | Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration |
|
|
|
| Secondary | Time to Maximum Change From Baseline Concentration (Tmax) of Glucagon | All enrolled participants that completed the required dosing visits with available pharmacokinetics (PK) data. Study dosing visits occurred on Day 0 and then again after the washout period between Day 7 to Day 28. | Posted | Median | Full Range | hours | Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration |
|
|
|
| Secondary | Area Under the Effect Concentration Time Curve (AUEC0-1.5) of Baseline-Adjusted Glucose From Time Zero up to 90 Minutes | All enrolled participants that completed the required dosing visits with available pharmacodynamics (PD) data. Study dosing visits occurred on Day 0 and then again after the washout period between Day 7 to Day 28. | Posted | Mean | Standard Deviation | hr*mg/dL | Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration |
|
|
|
| Secondary | Maximum Change From Baseline Concentration (Cmax) of Glucose | All enrolled participants that completed the required dosing visits with available pharmacodynamics (PD) data. Study dosing visits occurred on Day 0 and then again after the washout period between Day 7 to Day 28. | Posted | Mean | Standard Deviation | milligrams per deciliter (mg/dL) | Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration |
|
|
|
| Secondary | Time to Maximum Change From Baseline Concentration (Tmax) of Glucose | All enrolled participants that completed the required dosing visits with available pharmacodynamics (PD) data. Study dosing visits occurred on Day 0 and then again after the washout period between Day 7 to Day 28. | Posted | Median | Full Range | hours | Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration |
|
|
|
| 0 |
| 77 |
| 44 |
| 77 |
| EG001 | Intramuscular (IM) Glucagon | At a separate visit, 1 mg of IM glucagon. | 0 | 77 | 35 | 76 |
| Nausea | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | MedDRA 17.0 | Systematic Assessment |
|
| Eye pain | Eye disorders | MedDRA 17.0 | Systematic Assessment |
|
| Facial pain | General disorders | MedDRA 17.0 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
|
| Nasal discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
|
| Nasal edema | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 17.0 | Systematic Assessment |
|
| Lethargy | General disorders | MedDRA 17.0 | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
|
| Eye pruritus | Eye disorders | MedDRA 17.0 | Systematic Assessment |
|
| Lacrimation increased | Eye disorders | MedDRA 17.0 | Systematic Assessment |
|
| Ocular hyperemia | Eye disorders | MedDRA 17.0 | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA 17.0 | Systematic Assessment |
|
| Disturbance in attention | Psychiatric disorders | MedDRA 17.0 | Systematic Assessment |
|
| Somnolence | General disorders | MedDRA 17.0 | Systematic Assessment |
|
| Hot flush | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
|
| Hyperhidrosis | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
|
| Upper airway cough syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
|
| Hyperglycemia | Endocrine disorders | MedDRA 17.0 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 17.0 | Systematic Assessment |
|
| Headache | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
|
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| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| 30 minutes post glucagon administration |
|
| 60 minutes post glucagon administration |
|
| 90 minutes post glucagon administration |
|
| 30 minutes post glucagon administration |
|
| 45 minutes post glucagon administration |
|
| 60 minutes post glucagon administration |
|