Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2
Conditions
Brief summary
This study will investigate how the body processes nasal glucagon and the effect of nasal glucagon on the body. After an 8-hour overnight fast and 4 hours after the start of a low-carbohydrate breakfast, the study drug will be delivered into the participant's nostril(s) (intranasally) once or twice in each of four study periods. The study is open to adults with type 1 or type 2 diabetes and is expected to last about 50 days for each participant.
Interventions
DRUGNasal Glucagon
Administered intranasally.
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 70 Years
Healthy volunteers
No
Inclusion criteria
* Males or females with a history of Type 1 or Type 2 insulin-using diabetes of at least 1 year duration (basal only, basal bolus, meal-time only, or twice a day pre-mixed insulin) * A female participant must meet one of the following criteria: * Participant is of childbearing potential and agrees to use one of the accepted contraceptive regimens from at least 28 days prior to the first administration of the study drug, during the study and for at least 30 days after the last dose of the study drug. * Participant is of non-childbearing potential, defined as surgically sterile (i.e. has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or in a menopausal state (at least 1 year without menses) * Participants with a body mass index (BMI) greater than or equal to 18.50 kilograms per square meter (kg/m²) and below 35.00 kg/m² * Light-, non- or ex-smokers * 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
Exclusion criteria
* Females who are pregnant, actively attempting to get pregnant, or are lactating * History of significant hypersensitivity to glucagon or any related products as well as severe hypersensitivity reactions (such as angioedema) to any drugs * Presence of significant 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 * Suicidal tendency, history of or disposition to seizures, state of confusion, clinically relevant psychiatric diseases * Known presence of rare hereditary problems of galactose and /or lactose intolerance * Known presence or history of pheochromocytoma (i.e. adrenal gland tumor) or insulinoma (i.e. insulin secreting pancreas tumor) Presence of clinically significant findings on nasal examination or bilateral anterior rhinoscopy, such as structural abnormalities, nasal polyps, marked septal deviation, nasal tumors * Nasal surgery in the previous 28 days before Day 1 of this study * Daily use of a systemic beta-blocker drug, indomethacin, warfarin or anticholinergic drugs in the previous 28 days before Day 1 of this study * Any other concomitant maintenance therapy that would influence the outcome of the trial or compromise the safety of the participant, at the discretion of the Investigator and the Sponsor, in the previous 28 days before Day 1 of this study * Significant history of drug dependency or alcohol abuse * Any clinically significant illness in the previous 28 days before Day 1 of this study * Any history of tuberculosis and/or prophylaxis for tuberculosis * Positive urine screening of alcohol and/or drugs of abuse * Concurrent participation or intention of participating in another clinical trial during this study * Participants who took an Investigational Product (in another clinical trial) in the previous 28 days before Day 1 of this study or who have already participated in this clinical study * Participants who donated 50 milliliters (mL) or more of blood in the previous 28 days before Day 1 of this study * Donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical studies, etc.) in the previous 56 days before Day 1 of this study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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, 0.33, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2, 2.5, and 3 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, 0.33, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2, 2.5, and 3 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, 0.33, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2, 2.5, and 3 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, 0.33, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2, 2.5, and 3 hours post dose for each treatment |
| Pharmacodynamics (PD): Area Under the Effect Concentration Time Curve (AUEC₀-₁.₅) of Blood Glucose (BG) | Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.33, 0.5, 0.75, 1.0, 1.25, and 1.5 hours post dose for each treatment |
| PD: Time to Maximum Concentration (Tmax) of Baseline-Adjusted Glucose | Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.33, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2, 2.5, and 3 hours post dose for each treatment |
| PD: Baseline-Adjusted Glucose Maximum Concentration (BGmax) | Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.33, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2, 2.5, and 3 hours post dose for each treatment |
Countries
Canada
Participant flow
Recruitment details
4-period, 4 sequence, repeated single dose design with 7 days washout period between each dose.
Participants by arm
| Arm | Count |
|---|---|
| All Participants A minimum dose of 3 mg NG was administered. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 1 | Study Terminated (withdrawn by sponsor) | 3 | 3 | 3 | 3 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 41 years STANDARD_DEVIATION 13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| 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 | 1 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Region of Enrollment Canada | 12 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 7 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 / 3 | 2 / 3 | 3 / 3 | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 |
Outcome results
Primary
PD: Baseline-Adjusted Glucose Maximum Concentration (BGmax)
Time frame: Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.33, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2, 2.5, and 3 hours post dose for each treatment
Population: Zero participants analyzed due to the limited number of samples and the delivery of a potential sub-target dosing dose.
Primary
PD: Time to Maximum Concentration (Tmax) of Baseline-Adjusted Glucose
Time frame: Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.33, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2, 2.5, and 3 hours post dose for each treatment
Population: Zero participants analyzed due to the limited number of samples and the delivery of a potential sub-target dosing dose.
Primary
Pharmacodynamics (PD): Area Under the Effect Concentration Time Curve (AUEC₀-₁.₅) of Blood Glucose (BG)
Time frame: Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.33, 0.5, 0.75, 1.0, 1.25, and 1.5 hours post dose for each treatment
Population: Zero participants analyzed due to the limited number of samples and the delivery of a potential sub-target dosing dose.
Primary
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, 0.33, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2, 2.5, and 3 hours post dose for each treatment
Population: Zero participants analyzed due to the limited number of samples and the delivery of a potential sub-target dosing dose.
Primary
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, 0.33, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2, 2.5, and 3 hours post dose for each treatment
Population: Zero participants analyzed due to the limited number of samples and the delivery of a potential sub-target dosing dose.
Primary
PK: Maximum Change From Baseline Concentration (Cmax) of Glucagon
Time frame: Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.33, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2, 2.5, and 3 hours post dose for each treatment
Population: Zero participants analyzed due to the limited number of samples and the delivery of a potential sub-target dosing dose.
Primary
PK: Time to Maximum Concentration (Tmax) of Baseline Adjusted Glucagon
Time frame: Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.33, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2, 2.5, and 3 hours post dose for each treatment
Population: Zero participants analyzed due to the limited number of samples and the delivery of a potential sub-target dosing dose.