Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to determine the efficacy and safety of nasal glucagon compared to intramuscular (IM) glucagon for treatment of insulin-induced hypoglycemia in Japanese participants with diabetes mellitus.
Interventions
DRUGGlucagon Nasal Powder
Administered intranasally
DRUGGlucagon Hydrochloride Solution
Administered IM
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Participants with Type 1 diabetes (T1D) or Type 2 diabetes (T2D) * Body mass Index (BMI) of 18.5 to 30.0 kilograms per meter squared (kg/m2) for T1D, or 18.5 to 35.0 kg/m2 for T2D * Hemoglobin A1c (HbA1c) ≤10%
Exclusion criteria
* Have significant changes in insulin regimen and/ or unstable blood sugar control within the past 3 month * Have received a total daily dose of insulin \>1.2 units per kilogram (U/kg)
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 | Percentage of participants who achieved treatment success during the controlled insulin-induced hypoglycemia in participants with type 1 diabetes mellitus (T1DM) and participants with type 2 diabetes mellitus (T2DM).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 | Description |
|---|---|---|
| Pharmacodynamics (PD): Change From Baseline in Maximal Blood Glucose (BGmax) of Glucagon Nasal Powder and Glucagon Hydrochloride Intramuscular (IM) | Pre-dose, 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, 240 minutes after each glucagon administration | PD assessment measured the change from Baseline in maximal blood glucose (BGmax) of Glucagon Nasal Powder and Glucagon Hydrochloride intramuscular (IM). |
| PD: Time to Maximal Concentration (Tmax) of Glucagon Nasal Powder and Glucagon Hydrochloride IM | Pre-dose, 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, 240 minutes after each glucagon administration | PD assessment measured the time to maximal concentration (Tmax) of Glucagon Nasal Powder and Glucagon Hydrochloride IM. |
| Pharmacokinetics (PK): Change From Baseline in Area Under the Concentration Versus Time Curve From Zero to Time t (AUC [0-tLast]) of Glucagon Nasal Powder and Glucagon Hydrochloride IM | Pre-dose, 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, 240 minutes after each glucagon administration | PK assessment measured the change from baseline in the area under the concentration versus time curve from time zero to time t, where t is the last time point with a measurable concentration of Glucagon Nasal Powder and Glucagon Hydrochloride IM. |
| PK: Change From Baseline in Maximal Concentration (Cmax) of Glucagon Nasal Powder and Glucagon Hydrochloride IM | Pre-dose, 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, 240 minutes after each glucagon administration | PK assessment measured the change from baseline in maximal concentration (Cmax) of glucagon nasal powder and glucagon hydrochloride IM. |
| PK: Change From Baseline in Tmax of Glucagon Nasal Powder and Glucagon Hydrochloride IM | Pre-dose, 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, 240 minutes after each glucagon administration | PK assessment measured the change from baseline in Tmax of Glucagon Nasal Powder and Glucagon Hydrochloride IM. |
Countries
Japan
Participant flow
Pre-assignment details
Participants were randomized to receive either nasal glucagon or intramuscular (IM) glucagon in the first period, followed by the alternate treatment in the second period.
Participants by arm
| Arm | Count |
|---|---|
| Glucagon Nasal Powder/Glucagon Hydrochloride Solution A single dose of 3 mg glucagon nasal powder was administered intranasally | 33 |
| Glucagon Hydrochloride Solution/Glucagon Nasal Powder A single dose of 1 mg glucagon hydrochloride solution was administered IM | 39 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Did not receive treatment | 1 | 2 |
| Period 1 | Physician Decision | 1 | 1 |
| Period 1 | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Glucagon Nasal Powder/Glucagon Hydrochloride Solution | Total | Glucagon Hydrochloride Solution/Glucagon Nasal Powder |
|---|---|---|---|
| Age, Continuous | 41.7 years STANDARD_DEVIATION 11.6 | 50.2 years STANDARD_DEVIATION 13 | 57.5 years STANDARD_DEVIATION 9.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants | 72 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 33 Participants | 72 Participants | 39 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 33 participants | 72 participants | 39 participants |
| Sex: Female, Male Female | 13 Participants | 22 Participants | 9 Participants |
| Sex: Female, Male Male | 20 Participants | 50 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 71 | 0 / 70 |
| other Total, other adverse events | 15 / 71 | 13 / 70 |
| serious Total, serious adverse events | 0 / 71 | 1 / 70 |
Outcome results
Primary
Percentage of Participants Achieving Treatment Success During Controlled Insulin-Induced Hypoglycemia
Percentage of participants who achieved treatment success during the controlled insulin-induced hypoglycemia in participants with type 1 diabetes mellitus (T1DM) and participants with type 2 diabetes mellitus (T2DM).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 randomized participant who completed both treatment visits and had evaluable treatment success data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glucagon Nasal Powder | Percentage of Participants Achieving Treatment Success During Controlled Insulin-Induced Hypoglycemia | 100 percentage of participants |
| Glucagon Hydrochloride Solution | Percentage of Participants Achieving Treatment Success During Controlled Insulin-Induced Hypoglycemia | 100 percentage of participants |
95% CI: [-1.47, 1.47]
Secondary
PD: Time to Maximal Concentration (Tmax) of Glucagon Nasal Powder and Glucagon Hydrochloride IM
PD assessment measured the time to maximal concentration (Tmax) of Glucagon Nasal Powder and Glucagon Hydrochloride IM.
Time frame: Pre-dose, 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, 240 minutes after each glucagon administration
Population: All randomized participants who received at least one dose of study drug and had evaluable PD data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Glucagon Nasal Powder | PD: Time to Maximal Concentration (Tmax) of Glucagon Nasal Powder and Glucagon Hydrochloride IM | 1.00 hour |
| Glucagon Hydrochloride Solution | PD: Time to Maximal Concentration (Tmax) of Glucagon Nasal Powder and Glucagon Hydrochloride IM | 1.50 hour |
Secondary
Pharmacodynamics (PD): Change From Baseline in Maximal Blood Glucose (BGmax) of Glucagon Nasal Powder and Glucagon Hydrochloride Intramuscular (IM)
PD assessment measured the change from Baseline in maximal blood glucose (BGmax) of Glucagon Nasal Powder and Glucagon Hydrochloride intramuscular (IM).
Time frame: Pre-dose, 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, 240 minutes after each glucagon administration
Population: All randomized patients who receive at least 1 dose of the study drug and have evaluable PD data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Glucagon Nasal Powder | Pharmacodynamics (PD): Change From Baseline in Maximal Blood Glucose (BGmax) of Glucagon Nasal Powder and Glucagon Hydrochloride Intramuscular (IM) | 113 milligram/deciliter (mg/dL) | Geometric Coefficient of Variation 32 |
| Glucagon Hydrochloride Solution | Pharmacodynamics (PD): Change From Baseline in Maximal Blood Glucose (BGmax) of Glucagon Nasal Powder and Glucagon Hydrochloride Intramuscular (IM) | 119 milligram/deciliter (mg/dL) | Geometric Coefficient of Variation 33 |
Secondary
Pharmacokinetics (PK): Change From Baseline in Area Under the Concentration Versus Time Curve From Zero to Time t (AUC [0-tLast]) of Glucagon Nasal Powder and Glucagon Hydrochloride IM
PK assessment measured the change from baseline in the area under the concentration versus time curve from time zero to time t, where t is the last time point with a measurable concentration of Glucagon Nasal Powder and Glucagon Hydrochloride IM.
Time frame: Pre-dose, 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, 240 minutes after each glucagon administration
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Glucagon Nasal Powder | Pharmacokinetics (PK): Change From Baseline in Area Under the Concentration Versus Time Curve From Zero to Time t (AUC [0-tLast]) of Glucagon Nasal Powder and Glucagon Hydrochloride IM | 4830 Picogram*hour/milliliter (pg*h/mL) | Geometric Coefficient of Variation 89 |
| Glucagon Hydrochloride Solution | Pharmacokinetics (PK): Change From Baseline in Area Under the Concentration Versus Time Curve From Zero to Time t (AUC [0-tLast]) of Glucagon Nasal Powder and Glucagon Hydrochloride IM | 3240 Picogram*hour/milliliter (pg*h/mL) | Geometric Coefficient of Variation 32 |
Secondary
PK: Change From Baseline in Maximal Concentration (Cmax) of Glucagon Nasal Powder and Glucagon Hydrochloride IM
PK assessment measured the change from baseline in maximal concentration (Cmax) of glucagon nasal powder and glucagon hydrochloride IM.
Time frame: Pre-dose, 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, 240 minutes after each glucagon administration
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Glucagon Nasal Powder | PK: Change From Baseline in Maximal Concentration (Cmax) of Glucagon Nasal Powder and Glucagon Hydrochloride IM | 9520 picogram/milliliter (pg/mL) | Geometric Coefficient of Variation 103 |
| Glucagon Hydrochloride Solution | PK: Change From Baseline in Maximal Concentration (Cmax) of Glucagon Nasal Powder and Glucagon Hydrochloride IM | 3290 picogram/milliliter (pg/mL) | Geometric Coefficient of Variation 37 |
Secondary
PK: Change From Baseline in Tmax of Glucagon Nasal Powder and Glucagon Hydrochloride IM
PK assessment measured the change from baseline in Tmax of Glucagon Nasal Powder and Glucagon Hydrochloride IM.
Time frame: Pre-dose, 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, 240 minutes after each glucagon administration
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Glucagon Nasal Powder | PK: Change From Baseline in Tmax of Glucagon Nasal Powder and Glucagon Hydrochloride IM | 0.25 hour (h) |
| Glucagon Hydrochloride Solution | PK: Change From Baseline in Tmax of Glucagon Nasal Powder and Glucagon Hydrochloride IM | 0.17 hour (h) |