Safety and Efficacy of ZP-Glucagon to Injectable Glucagon for Hypoglycemia

Study Overview
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Brief Summary
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The purpose of this study is to determine whether glucagon administered by microneedle patch is comparable to glucagon administered by injection pen in the treatment of insulin-induced hypoglycemia.

Detailed Description
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The purpose of this study is to compare ZP-Glucagon transdermal patch system at doses of 0.5 mg and 1 mg to glucagon by injection at doses of 0.5 mg and 1 mg by means of a 4 way crossover open label design. Eligible subjects giving informed consent will be randomised to a treatment sequence of each of the four treatments in one week intervals. At each treatment visit, subjects will undergo an insulin induction procedure designed to safely induce hypoglycemia, and then have a treatment applied, either by injection or by patch, and then monitored for return to normoglycemia.

Official Title
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A Randomized Open-label Crossover Study to Compare the Safety and Efficacy of ZP-Glucagon to Injectable Glucagon in the Treatment of Insulin-induced Hypoglycemia in Subjects With Type-1 Diabetes

Conditions
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Hypoglycemia

Intervention / Treatment
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* Drug: Glucagon (ZP-Glucagon)
* Drug: Glucagon (GlucaGen)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women or men 18 to 60 years with type-1 diabetes on daily insulin treatment (basal-bolus injection regimen or insulin pump) for at least two years, on a total daily dose that has been stable for the last 3 months preceding enrollment (no more than 20% variation), and with a current level of glycated hemoglobin between 6.5% and 10% Exclusion Criteria: Any history of hypoglycemic coma or hypoglycemic seizures. Any episode of severe hypoglycemia (requiring treatment) within one month prior to study start. Any history of pheochromocytoma or insulinoma

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ZP-Glucagon 0.5 mg<br>glucagon applied to the ZP transdermal microneedle patch system at a dose of 0.5 mg applied by means of a purpose built reusable applicator and worn for 30 minutes | Drug: Glucagon (ZP-Glucagon)<br>* chemically synthesized glucagon as delivered via transdermal microneedle patch system for 30 minutes<br>* Other names: glucagon;|
| Experimental: ZP-Glucagon 1.0 mg<br>glucagon applied to the ZP transdermal microneedle patch system at a dose of 1.0 mg applied by means of a purpose built reusable applicator and worn for 30 minutes | Drug: Glucagon (ZP-Glucagon)<br>* chemically synthesized glucagon as delivered via transdermal microneedle patch system for 30 minutes<br>* Other names: glucagon;|
| Active Comparator: Glucagon by injection, 0.5 mg<br>glucagon applied as GlucaGen (NovoNordisk) injector system at a dose of 0.5 mg | Drug: Glucagon (GlucaGen)<br>* recombinant glucagon administered via subcutaneous injection<br>* Other names: glucagon;|
| Active Comparator: Glucagon by injection, 1.0 mg<br>glucagon applied as GlucaGen (NovoNordisk) injector system at a dose of 0.5 mg | Drug: Glucagon (GlucaGen)<br>* recombinant glucagon administered via subcutaneous injection<br>* Other names: glucagon;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects achieving normoglycemia |  | 30 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time at which normoglycemia is first reached |  | 3 hours | 
| Time at which maximal glucose levels are reached |  | 3 hours | 
| Increases in blood glucose by 15 minute intervals |  | 3 hours | 
| Peak Plasma Concentration (Cmax) |  | 3 hours | 
| Area under the plasma concentration versus time curve (AUC) |  | 3 hours |