Healthy
Conditions
Brief summary
The main purpose of this study was to evaluate the safety and tolerability of nasal glucagon (NG). The study drug was delivered into the participant's nostril (intranasally) or was given as an injection just under the skin (subcutaneously) once in each of four study periods. The study lasted about 23 days for each participant.
Interventions
DRUGNasal Glucagon
Administered intranasally.
DRUGGlucagon
Administered SC.
Sponsors
Locemia Solutions ULC
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Body mass index (BMI) greater than or equal to 20.00 and below or equal to 28.00 kg/m². * Light-, non- or ex-smokers. * Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on physical examination and/or clinical laboratory evaluations (hematology, biochemistry, ECG and urinalysis).
Exclusion criteria
* Presence of any nose piercings. * History of significant hypersensitivity to glucagon or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs. * Presence of significant gastrointestinal, liver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects. * Presence of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease. * Presence of clinically significant findings on nasal examination and bilateral anterior rhinoscopy. * Fasting blood glucose above 5.0 millimoles per liter (mmol/L) at screening, following a 12-hour fasting period. * Fasting blood glucose assessed with a glucose meter above 5.5 mmol/L 0.5 hour before each dosing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One or More Serious Adverse Event(s) (SAEs) | Baseline through Study Completion (Day 23) | Safety and tolerability evaluated through the assessment of adverse events. A SAE (serious adverse event) was defined as any untoward medical occurrence in a clinical investigation, which did not necessarily have a causal relationship with this treatment. A summary of other non-serious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section. |
Secondary
| Measure | Time frame |
|---|---|
| PD: Time to Maximum Concentration (Tmax) of Baseline-Adjusted Glucose | Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to T (AUC[0-tlast]) of Baseline Adjusted Glucagon | Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment |
| PK: Area Under the Curve Extrapolated to Infinity (AUC[0-inf]) of Baseline Adjusted Glucagon | Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment |
| Pharmacodynamics (PD): Area Under the Effect Concentration Time Curve (AUEC₀-₄) of Glucose | Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment |
| PK: Maximum Change From Baseline Concentration (Cmax) of Glucagon | Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment |
| PD: Baseline-Adjusted Glucose Maximum Concentration (BGmax) | Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment |
| PK: Time to Maximum Concentration (Tmax) of Baseline Adjusted Glucagon | Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment |
Countries
Canada
Participant flow
Recruitment details
This was a four-period crossover study in which participants received a single dose of study drug in each period, with seven days between each dose.
Participants by arm
| Arm | Count |
|---|---|
| All Participants In each of four study periods, a single dose of either NG or SC glucagon was administered. | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 33 years STANDARD_DEVIATION 9 |
| Race/Ethnicity, Customized Black | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 14 Participants |
| Region of Enrollment Canada | 16 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 15 | 6 / 14 | 8 / 16 | 6 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 14 | 0 / 16 | 0 / 15 |
Outcome results
Primary
Number of Participants With One or More Serious Adverse Event(s) (SAEs)
Safety and tolerability evaluated through the assessment of adverse events. A SAE (serious adverse event) was defined as any untoward medical occurrence in a clinical investigation, which did not necessarily have a causal relationship with this treatment. A summary of other non-serious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
Time frame: Baseline through Study Completion (Day 23)
Population: All randomized participants who entered study period four.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NG 0.5 mg | Number of Participants With One or More Serious Adverse Event(s) (SAEs) | 0 Participants |
| NG 1 mg | Number of Participants With One or More Serious Adverse Event(s) (SAEs) | 0 Participants |
| NG 2 mg | Number of Participants With One or More Serious Adverse Event(s) (SAEs) | 0 Participants |
| SC Glucagon 1 mg | Number of Participants With One or More Serious Adverse Event(s) (SAEs) | 0 Participants |
Secondary
PD: Baseline-Adjusted Glucose Maximum Concentration (BGmax)
Time frame: Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment
Population: All randomized participants with evaluable PD data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NG 0.5 mg | PD: Baseline-Adjusted Glucose Maximum Concentration (BGmax) | 0.811 millimole per liter (mmol/L) | Standard Error 0.119 |
| NG 1 mg | PD: Baseline-Adjusted Glucose Maximum Concentration (BGmax) | 1.92 millimole per liter (mmol/L) | Standard Error 0.173 |
| NG 2 mg | PD: Baseline-Adjusted Glucose Maximum Concentration (BGmax) | 3.20 millimole per liter (mmol/L) | Standard Error 0.252 |
| SC Glucagon 1 mg | PD: Baseline-Adjusted Glucose Maximum Concentration (BGmax) | 3.28 millimole per liter (mmol/L) | Standard Error 0.326 |
Secondary
PD: Time to Maximum Concentration (Tmax) of Baseline-Adjusted Glucose
Time frame: Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment
Population: All randomized participants with evaluable PD data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NG 0.5 mg | PD: Time to Maximum Concentration (Tmax) of Baseline-Adjusted Glucose | 0.33 hour (h) |
| NG 1 mg | PD: Time to Maximum Concentration (Tmax) of Baseline-Adjusted Glucose | 0.36 hour (h) |
| NG 2 mg | PD: Time to Maximum Concentration (Tmax) of Baseline-Adjusted Glucose | 0.50 hour (h) |
| SC Glucagon 1 mg | PD: Time to Maximum Concentration (Tmax) of Baseline-Adjusted Glucose | 0.37 hour (h) |
Secondary
Pharmacodynamics (PD): Area Under the Effect Concentration Time Curve (AUEC₀-₄) of Glucose
Time frame: Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment
Population: All randomized participants with evaluable PD data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NG 0.5 mg | Pharmacodynamics (PD): Area Under the Effect Concentration Time Curve (AUEC₀-₄) of Glucose | -0.168 millimole*hour per liter (mmol*h/L) | Standard Error 0.202 |
| NG 1 mg | Pharmacodynamics (PD): Area Under the Effect Concentration Time Curve (AUEC₀-₄) of Glucose | 0.0617 millimole*hour per liter (mmol*h/L) | Standard Error 0.177 |
| NG 2 mg | Pharmacodynamics (PD): Area Under the Effect Concentration Time Curve (AUEC₀-₄) of Glucose | 0.566 millimole*hour per liter (mmol*h/L) | Standard Error 0.324 |
| SC Glucagon 1 mg | Pharmacodynamics (PD): Area Under the Effect Concentration Time Curve (AUEC₀-₄) of Glucose | 0.448 millimole*hour per liter (mmol*h/L) | Standard Error 0.49 |
Secondary
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to T (AUC[0-tlast]) of Baseline Adjusted Glucagon
Time frame: Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment
Population: All randomized participants with evaluable PK data. In the NG 0.5 mg arm, all participants had serum glucagon levels that were below the lower limit of quantification (100 picogram per milliliter \[pg/mL\]) except for one participant at one time point.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| NG 0.5 mg | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to T (AUC[0-tlast]) of Baseline Adjusted Glucagon | NA picogram*hour per milliliter (pg*h/mL) | — |
| NG 1 mg | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to T (AUC[0-tlast]) of Baseline Adjusted Glucagon | 38.9 picogram*hour per milliliter (pg*h/mL) | Geometric Coefficient of Variation 483 |
| NG 2 mg | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to T (AUC[0-tlast]) of Baseline Adjusted Glucagon | 293 picogram*hour per milliliter (pg*h/mL) | Geometric Coefficient of Variation 172 |
| SC Glucagon 1 mg | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to T (AUC[0-tlast]) of Baseline Adjusted Glucagon | 2060 picogram*hour per milliliter (pg*h/mL) | Geometric Coefficient of Variation 68 |
Secondary
PK: Area Under the Curve Extrapolated to Infinity (AUC[0-inf]) of Baseline Adjusted Glucagon
Time frame: Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment
Population: All randomized participants with evaluable PK data. AUC(0-inf) could not be calculated for the NG 0.5 mg arm, because all participants had serum glucagon levels below the lower limit of quantification (100 pg/mL) except for one participant at one time point.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| NG 1 mg | PK: Area Under the Curve Extrapolated to Infinity (AUC[0-inf]) of Baseline Adjusted Glucagon | NA pg*h/mL | — |
| NG 2 mg | PK: Area Under the Curve Extrapolated to Infinity (AUC[0-inf]) of Baseline Adjusted Glucagon | 589 pg*h/mL | Geometric Coefficient of Variation 50 |
| SC Glucagon 1 mg | PK: Area Under the Curve Extrapolated to Infinity (AUC[0-inf]) of Baseline Adjusted Glucagon | 2250 pg*h/mL | Geometric Coefficient of Variation 66 |
Secondary
PK: Maximum Change From Baseline Concentration (Cmax) of Glucagon
Time frame: Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment
Population: All randomized participants with evaluable PK data. In the NG 0.5 mg arm, all participants had serum glucagon levels that were below the lower limit of quantification (100 pg/mL) except for one participant at one time point.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| NG 0.5 mg | PK: Maximum Change From Baseline Concentration (Cmax) of Glucagon | NA picogram per milliliter (pg/mL) | — |
| NG 1 mg | PK: Maximum Change From Baseline Concentration (Cmax) of Glucagon | 217 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 231 |
| NG 2 mg | PK: Maximum Change From Baseline Concentration (Cmax) of Glucagon | 1000 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 104 |
| SC Glucagon 1 mg | PK: Maximum Change From Baseline Concentration (Cmax) of Glucagon | 3260 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 59 |
Secondary
PK: Time to Maximum Concentration (Tmax) of Baseline Adjusted Glucagon
Time frame: Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment
Population: All randomized participants with evaluable PK data. In the NG 0.5 mg arm, all participants had serum glucagon levels that were below the lower limit of quantification (100 pg/mL) except for one participant at one time point.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NG 0.5 mg | PK: Time to Maximum Concentration (Tmax) of Baseline Adjusted Glucagon | 0.17 hour (h) |
| NG 1 mg | PK: Time to Maximum Concentration (Tmax) of Baseline Adjusted Glucagon | 0.25 hour (h) |
| NG 2 mg | PK: Time to Maximum Concentration (Tmax) of Baseline Adjusted Glucagon | 0.25 hour (h) |
| SC Glucagon 1 mg | PK: Time to Maximum Concentration (Tmax) of Baseline Adjusted Glucagon | 0.33 hour (h) |