Pharmacokinetics and Pharmacodynamics of BIOD-961 vs. Marketed Glucagons

Study Overview
=================
Brief Summary
-----------------
BIOD-961 is a dry powder formulation of glucagon intended for use in a device that mixes (reconstitutes) the powder with liquid to make it easier for users to treat patients with severe hypoglycemia. The purpose of this study is to evaluate how much BIOD-961 absorbs into the bloodstream, how much it raises glucose concentrations (the intended effect) and compare to two glucagon products already on the market.

Detailed Description
-----------------
Subjects receive on separate days, in random order one of the following: 1 mg BIOD-961 intramuscularly (IM), 1 mg Lilly (IM), 1 mg Novo (IM), 1 mg BIOD-961 subcutaneously (SC), 1 mg Lilly (SC), and 1 mg Novo (SC).

Official Title
-----------------
Pharmacokinetics and Pharmacodynamics of BIOD-961 vs. Glucagon for Injection (Eli Lilly) and GlucaGen® (Novo Nordisk) Administered by Subcutaneous and Intramuscular Injection in Normal, Healthy Volunteers

Conditions
-----------------
Hypoglycemia

Intervention / Treatment
-----------------
* Drug: BIOD-961
* Drug: Lilly Glucagon
* Drug: Novo Glucagon


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Body Mass Index: 18.5-25.0 kg/m2 inclusive. Subject has provided informed consent and has signed and dated an informed consent form before any trial-related activities. Exclusion Criteria: Type 1 or type 2 diabetes mellitus. History of pheochromocytoma, insulinoma, glucagonoma, or glycogen storage disease. History of regular alcohol consumption as defined by alcohol intake exceeding 7 drinks per week for females or 14 drinks per week for males, where 1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor. Significant cardiovascular (to include New York Heart Association (NYHA) Class III or- IV functional capacity or uncontrolled hypertension), respiratory, gastrointestinal, hepatic, renal, neurological, psychiatric and/or hematological disease. Any significant cardiovascular event history, including angina, myocardial infarction, therapeutic coronary procedure (e.g, percutaneous transluminal coronary angioplasty, coronary bypass surgery), stroke, or transient ischemic attack. Females who are breast feeding, pregnant, or intending to become pregnant during the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIOD-961, 1 mg IM<br>Intramuscular delivery of BIOD-961. | Drug: BIOD-961<br>* BIOD-961 is a lyophilized glucagon formulation.<br>|
| Active Comparator: Lilly Glucagon, 1 mg IM<br>Intramuscular delivery of Lilly glucagon. | Drug: Lilly Glucagon<br> <br> |
| Active Comparator: Novo Glucagon, 1 mg IM<br>Intramuscular delivery of Novo glucagon. | Drug: Novo Glucagon<br> <br> |
| Experimental: BIOD-961, 1 mg SC<br>Subcutaneous delivery of BIOD-961, | Drug: BIOD-961<br>* BIOD-961 is a lyophilized glucagon formulation.<br>|
| Active Comparator: Lilly Glucagon, 1 mg SC<br>Subcutaneous delivery of Lilly glucagon. | Drug: Lilly Glucagon<br> <br> |
| Active Comparator: Novo Glucagon, 1 mg SC<br>Subcutaneous delivery of Novo glucagon. | Drug: Novo Glucagon<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucagon maximal concentration and area under curve |  | 240 minutes post dose | 
| Glucose maximal concentration and area under curve |  | 240 minutes after dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to maximal glucagon concentration |  | 240 minutes after dose | 
| Time to maximal glucose concentration |  | 240 minutes after dose | 
| Maximal glucose excursion |  | 240 minutes after dose | 
| Area under the glucose time curve from 0 to return to baseline after blood glucose peaked |  | 240 minutes after dose |