A Study of Nasal Glucagon in Participants With Type 1 Diabetes Mellitus

Study Overview
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Brief Summary
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The purpose of this study is to compare a needle-free treatment of hypoglycemia with nasal glucagon (study drug) to a marketed glucagon administered by the intramuscular (IM) route, in participants with type 1 diabetes mellitus (T1DM).

Official Title
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Comparison of Glucagon Administered by Either the Nasal (LY900018) or Intra-muscular (GlucaGen®) Routes in Adult Patients With Type 1 Diabetes Mellitus During Controlled Insulin-Induced Hypoglycemia

Conditions
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Hypoglycemia, Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: Nasal Glucagon
* Drug: Intramuscular Glucagon


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Type 1 Diabetes Mellitus (T1DM) for at least 2 years and receiving daily insulin since the time of diagnosis Exclusion Criteria: Have a history of hypersensitivity to glucagon or any related products or severe hypersensitivity reactions (such as angioedema) to any drugs Have a history of pheochromocytoma (that is, adrenal gland tumor) or insulinoma Occurrence of an episode of severe hypoglycemia (defined as requiring the assistance of another person in the 1 month prior to enrolling in the study) Have a history of epilepsy or seizure disorder Are women who are pregnant or lactating Have, except for the current regimen of insulin therapy and concomitant medication, regular use of or intended use of any over-the-counter or prescription medications or nutritional supplements that treat hyperglycemia or insulin resistance or that promote weight loss within 14 days before dosing Daily use of systemic beta-blocker, indomethacin, warfarin or anticholinergic drugs Require daily insulin treatment greater than (>)1.5 unit/kilograms (U/kg)/body weight

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nasal Glucagon<br>Single dose of Nasal Glucagon. | Drug: Nasal Glucagon<br>* Administered nasally<br>* Other names: LY900018;|
| Active Comparator: Intramuscular Glucagon<br>Single intramuscular (IM) dose of Glucagon. | Drug: Intramuscular Glucagon<br>* Administered IM<br>* Other names: GlucaGen®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Treatment Success During Controlled Insulin-Induced Hypoglycemia | Treatment success is defined as an increase in plasma glucose to greater than or equal to (≥) 70 milligrams per deciliter (mg/dL) or an increase of ≥20 mg/dL from plasma glucose nadir, without receiving additional actions to increase the plasma glucose concentration. Nadir is defined as the minimum plasma glucose concentration at the time of or within 10 minutes following glucagon administration. | Pre-dose up to 30 minutes post each glucagon administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamics (PD): Change From Baseline in Maximal Blood Glucose (BGmax) |  | Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60, and 90 minutes after glucagon administration | 
| PD: Time to Maximum Concentration (Tmax) of Baseline-Adjusted Glucose |  | Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60, and 90 minutes after glucagon administration | 
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Tlast (AUC[0-tlast]) of Baseline Adjusted Glucagon |  | Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, and 240 minutes after glucagon administration | 
| PK: Maximum Change From Baseline Concentration (Cmax) of Glucagon |  | Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, and 240 minutes after glucagon administration | 
| PK: Time to Maximum Concentration (Tmax) of Baseline Adjusted Glucagon |  | Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, and 240 minutes after glucagon administration |