Diabetes Mellitus, Type 2
Conditions
Brief summary
This study evaluates a new formulation of insulin lispro, LY900014, a drug that lowers blood sugar. It is administered by injection into the vein and under the skin of the abdomen, thigh and arm. The study will be conducted in healthy people to investigate the effect of different injection sites on the amount of insulin lispro in the bloodstream. Side effects and tolerability will be documented. The study will last for about 10 weeks for each participant, including screening and follow up. Screening is required within 28 days prior to entering the study.
Interventions
DRUGLY900014 (SC)
Administered SC
DRUGLY900014 (IV)
Administered IV
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Overtly healthy male or a female (not pregnant and agreeable to take birth control measures until study completion) * Have a body mass index (BMI) of 18 to 30 kilogram per square meter (kg/m²) * Have normal blood pressure, pulse rate, electrocardiogram (ECG), blood and urine laboratory test results that are acceptable for the study * Are nonsmokers, have not smoked for at least 6 months prior to entering the study
Exclusion criteria
* Are currently participating in or completed a clinical trial within the last 30 days or any other type of medical research judged to be incompatible with this study * Have previously participated or withdrawn from this study * Had blood loss of more than 450 milliliters (mL) within the last 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) Following LY900014 Administration | Day 1: Pre-dose, 2.5, 5, 10, 15, 20, 25, 30, 40, 60, 70, 90, 120, 150, 180, 210, 240, 300, 360, 420, 480, 540, and 600 minutes post-dose | Pharmacokinetics(PK): Insulin lispro AUC from time zero to 10 hours post dose \[AUC(0-10h)\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Amount of Glucose Infused (Gtot) Over Duration of the Clamp Procedure | Every 10 minutes for 30 minutes predose, every 2.5 minutes for 30 minutes, then every 5 minutes for 120 minutes, then every 10 minutes for 120 to 480 minutes and every 10 minutes for 480 to 600 minutes post-dose | Glucodynamics: Gtot is the total glucose infusion over the clamp duration (10 hours) and is used to measure the study drug action over time as measured by the euglycemic clamp procedure. During the euglycemic clamp procedure, blood glucose concentrations are held constant after the administration of LY900014 by adjusting the exogenous glucose infusion rate. |
Countries
Singapore
Participant flow
Pre-assignment details
This is an open-label, randomized, crossover, up to 10-hour euglycemic clamp study in which participants were randomized into one of four treatment sequences. Participants received single doses of 15 units of LY900014 on 4 occasions (treatment Periods 1 through 4) with a wash-out period of at least 3 days between study drug administration.
Participants by arm
| Arm | Count |
|---|---|
| Overall Single 15-U dose of LY900014 administered in treatment Period 1- 4, as SC injection into the abdomen, the thigh, the deltoid or an IV bolus injection, per randomized treatment sequence. | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 1 | Physician Decision | 0 | 0 | 1 | 0 |
| Period 4 | Withdrawal by Subject | 1 | 0 | 0 | 0 |
| Washout Period 2 | Physician Decision | 0 | 0 | 1 | 0 |
| Washout Period 2 | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Overall |
|---|---|
| Age, Continuous | 39.8 years STANDARD_DEVIATION 8.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 28 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 | 0 Participants |
| Region of Enrollment Singapore | 28 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 28 Participants |
| Weight | 70.11 kilograms (kg) STANDARD_DEVIATION 10.48 |
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 | 0 / 25 | 0 / 26 | 0 / 26 | 0 / 28 |
| other Total, other adverse events | 6 / 25 | 7 / 26 | 11 / 26 | 4 / 28 |
| serious Total, serious adverse events | 0 / 25 | 0 / 26 | 0 / 26 | 0 / 28 |
Outcome results
Primary
Pharmacokinetics: Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) Following LY900014 Administration
Pharmacokinetics(PK): Insulin lispro AUC from time zero to 10 hours post dose \[AUC(0-10h)\].
Time frame: Day 1: Pre-dose, 2.5, 5, 10, 15, 20, 25, 30, 40, 60, 70, 90, 120, 150, 180, 210, 240, 300, 360, 420, 480, 540, and 600 minutes post-dose
Population: All participants who have received at least one dose of study drug and have measurable insulin lispro concentrations and evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY900014 (SC Abdomen) | Pharmacokinetics: Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) Following LY900014 Administration | 1760 picomole * hour/Liter (pmol * hr/L) | Geometric Coefficient of Variation 20 |
| LY900014 (SC Deltoid) | Pharmacokinetics: Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) Following LY900014 Administration | 1800 picomole * hour/Liter (pmol * hr/L) | Geometric Coefficient of Variation 16 |
| LY900014 (IV) | Pharmacokinetics: Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) Following LY900014 Administration | 2770 picomole * hour/Liter (pmol * hr/L) | Geometric Coefficient of Variation 22 |
| LY900014 (SC Thigh) | Pharmacokinetics: Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) Following LY900014 Administration | 1750 picomole * hour/Liter (pmol * hr/L) | Geometric Coefficient of Variation 19 |
Comparison: Geometric Least Squares Means (LSMeans) were controlled for injection site, study period, and sequence as fixed effects, and subject within sequence as a random effect.90% CI: [0.992, 1.07]Mixed Models Analysis
Comparison: Geometric LSMeans were controlled for injection site, study period, and sequence as fixed effects, and subject within sequence as a random effect.90% CI: [0.962, 1.04]Mixed Models Analysis
Secondary
Total Amount of Glucose Infused (Gtot) Over Duration of the Clamp Procedure
Glucodynamics: Gtot is the total glucose infusion over the clamp duration (10 hours) and is used to measure the study drug action over time as measured by the euglycemic clamp procedure. During the euglycemic clamp procedure, blood glucose concentrations are held constant after the administration of LY900014 by adjusting the exogenous glucose infusion rate.
Time frame: Every 10 minutes for 30 minutes predose, every 2.5 minutes for 30 minutes, then every 5 minutes for 120 minutes, then every 10 minutes for 120 to 480 minutes and every 10 minutes for 480 to 600 minutes post-dose
Population: All participants who have received at least one dose of study drug administered and have completed at least one clamp procedure. The IV treatment arm was needed only for PK as it served as the reference to determine the absolute bioavailability.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY900014 (SC Abdomen) | Total Amount of Glucose Infused (Gtot) Over Duration of the Clamp Procedure | 1490 milligram per kilogram (mg/kg) | Geometric Coefficient of Variation 45 |
| LY900014 (SC Deltoid) | Total Amount of Glucose Infused (Gtot) Over Duration of the Clamp Procedure | 1630 milligram per kilogram (mg/kg) | Geometric Coefficient of Variation 50 |
| LY900014 (IV) | Total Amount of Glucose Infused (Gtot) Over Duration of the Clamp Procedure | 1730 milligram per kilogram (mg/kg) | Geometric Coefficient of Variation 38 |
Comparison: Geometric LSMeans were controlled for injection site, study period, and sequence as fixed effects, and subject within sequence as a random effect.90% CI: [1, 1.2]Mixed Models Analysis
Comparison: Geometric LSMeans were controlled for injection site, study period, and sequence as fixed effects, and subject within sequence as a random effect.90% CI: [1.04, 1.25]Mixed Models Analysis