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

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.

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