Hypoglycemia, Diabetes Mellitus, Type 1
Conditions
Brief summary
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).
Interventions
DRUGNasal Glucagon
Administered nasally
Administered IM
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Treatment Success During Controlled Insulin-Induced Hypoglycemia | Pre-dose up to 30 minutes post each glucagon administration | 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. |
Secondary
| Measure | 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 |
Countries
Germany
Participant flow
Pre-assignment details
In each period, either 3 milligram (mg) nasal glucagon (NG) or 1 mg intramuscular (IM) Glucagon was administered. After a wash-out period of at least 1 day (24 hours) from the first period (first visit), participants crossed over to the alternate glucagon treatment in period 2 (second visit).
Participants by arm
| Arm | Count |
|---|---|
| Glucagon All enrolled participants who received either 3 mg NG or 1 mg IM Glucagon. | 70 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Visit of Glucagon Treatment | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Glucagon |
|---|---|
| Age, Continuous | 41.7 years STANDARD_DEVIATION 12.7 |
| Body Mass Index (BMI) | 25.53 kilogram per square meter (kg/m2) STANDARD_DEVIATION 2.97 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 70 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 175.21 Centimeter (cm) STANDARD_DEVIATION 8.43 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 70 Participants |
| Region of Enrollment Germany | 70 participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 43 Participants |
| Weight | 78.79 Kilogram (kg) STANDARD_DEVIATION 13.28 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 70 | 0 / 69 |
| other Total, other adverse events | 34 / 70 | 35 / 69 |
| serious Total, serious adverse events | 0 / 70 | 0 / 69 |
Outcome results
Primary
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.
Time frame: Pre-dose up to 30 minutes post each glucagon administration
Population: All participants who completed both treatment visits with evaluable data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nasal Glucagon (NG) | Percentage of Participants Achieving Treatment Success During Controlled Insulin-Induced Hypoglycemia | 66 Participants |
| IM Glucagon | Percentage of Participants Achieving Treatment Success During Controlled Insulin-Induced Hypoglycemia | 66 Participants |
95% CI: [-1.52, 1.52]
Secondary
PD: Time to Maximum Concentration (Tmax) of Baseline-Adjusted Glucose
Time frame: Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60, and 90 minutes after glucagon administration
Population: All enrolled participants who received at least 1 dose of the study drug with evaluable PD data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nasal Glucagon (NG) | PD: Time to Maximum Concentration (Tmax) of Baseline-Adjusted Glucose | 1.00 Hour (hr) |
| IM Glucagon | PD: Time to Maximum Concentration (Tmax) of Baseline-Adjusted Glucose | 1.50 Hour (hr) |
Secondary
Pharmacodynamics (PD): Change From Baseline in Maximal Blood Glucose (BGmax)
Time frame: Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60, and 90 minutes after glucagon administration
Population: All enrolled participants who received at least 1 dose of the study drug with evaluable PD data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nasal Glucagon (NG) | Pharmacodynamics (PD): Change From Baseline in Maximal Blood Glucose (BGmax) | 132 Milligrams per deciliter (mg/dL) | Geometric Coefficient of Variation 36 |
| IM Glucagon | Pharmacodynamics (PD): Change From Baseline in Maximal Blood Glucose (BGmax) | 161 Milligrams per deciliter (mg/dL) | Geometric Coefficient of Variation 29 |
Secondary
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Tlast (AUC[0-tlast]) of Baseline Adjusted Glucagon
Time frame: Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, and 240 minutes after glucagon administration
Population: All enrolled participants who received at least 1 dose of the study drug with evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nasal Glucagon (NG) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Tlast (AUC[0-tlast]) of Baseline Adjusted Glucagon | 2740 picogram*hour per millilitre (pg*hr/mL) | Geometric Coefficient of Variation 68 |
| IM Glucagon | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Tlast (AUC[0-tlast]) of Baseline Adjusted Glucagon | 3320 picogram*hour per millilitre (pg*hr/mL) | Geometric Coefficient of Variation 40 |
Secondary
PK: Maximum Change From Baseline Concentration (Cmax) of Glucagon
Time frame: Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, and 240 minutes after glucagon administration
Population: All enrolled participants who received at least 1 dose of the study drug with evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nasal Glucagon (NG) | PK: Maximum Change From Baseline Concentration (Cmax) of Glucagon | 6130 picograms per millilitre (pg/mL) | Geometric Coefficient of Variation 74 |
| IM Glucagon | PK: Maximum Change From Baseline Concentration (Cmax) of Glucagon | 3750 picograms per millilitre (pg/mL) | Geometric Coefficient of Variation 44 |
Secondary
PK: Time to Maximum Concentration (Tmax) of Baseline Adjusted Glucagon
Time frame: Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, and 240 minutes after glucagon administration
Population: All enrolled participants who received at least 1 dose of the study drug with evaluable PK data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nasal Glucagon (NG) | PK: Time to Maximum Concentration (Tmax) of Baseline Adjusted Glucagon | 0.25 Hour (hr) |
| IM Glucagon | PK: Time to Maximum Concentration (Tmax) of Baseline Adjusted Glucagon | 0.25 Hour (hr) |