Diabetes Mellitus, Type 2
Conditions
Brief summary
This study compares LY900014, a drug that lowers blood sugar, with insulin lispro (Humalog). Both drugs are given by injection under the skin of the abdomen. The study will be conducted in healthy people to investigate how quickly and how much LY900014 is absorbed and the effect of different doses of LY900014 on blood sugar levels in comparison with insulin lispro. The study will last about 7 to 12 weeks for each participant, including screening and follow up. Screening is required within 28 days prior to entering the study.
Interventions
DRUGLY900014
Administered SC
DRUGInsulin Lispro
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male or a female (not pregnant and agreeable to take birth control measures until one month after 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 * 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Are currently participating in or completed a clinical trial within the last 30 days * Have previously participated or withdrawn from this study * Have donated blood or have blood loss of more than 500 mL within the past 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) | Day 1: Pre-dose, 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 70, 90, 120, 150, 180, 210, 240, 300, 360, 420, 480, 540, and 600 minutes post-dose | Pharmacokinetics: Insulin Lispro Area Under the Concentration Curve From Time Zero to 10 Hours Post Dose \[AUC(0-10h)\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glucodynamics: Total Amount of Glucose Infused (Gtot) | Day 1: Every minute starting from the pre-dose and throughout the duration of the clamp until 10 hours post-dose | Glucodynamics: Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp |
Countries
Germany
Participant flow
Pre-assignment details
This was a 6-period crossover study in which participants received a single 7 Unit (U), 15 U, or 30 U subcutaneous (SC) dose of LY900014 or Humalog in one of six sequences. There was a washout period of ≥ 3 days between each euglycemic clamp procedure.
Participants by arm
| Arm | Count |
|---|---|
| Overall All participants who received at least on dose of study drug. | 42 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Washout Period 1 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 |
| Washout Period 2 | Personal Reasons | 0 | 1 | 0 | 0 | 0 | 0 |
| Washout Period 5 | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Overall |
|---|---|
| Age, Continuous | 41.9 years STANDARD_DEVIATION 11.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 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 | 40 Participants |
| Region of Enrollment Germany | 42 participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 40 | 0 / 41 | 0 / 40 | 0 / 41 | 0 / 40 |
| other Total, other adverse events | 7 / 40 | 5 / 40 | 14 / 41 | 8 / 40 | 6 / 41 | 5 / 40 |
| serious Total, serious adverse events | 0 / 40 | 0 / 40 | 0 / 41 | 0 / 40 | 0 / 41 | 0 / 40 |
Outcome results
Primary
Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Versus Time Curve (AUC)
Pharmacokinetics: Insulin Lispro Area Under the Concentration Curve From Time Zero to 10 Hours Post Dose \[AUC(0-10h)\]
Time frame: Day 1: Pre-dose, 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 70, 90, 120, 150, 180, 210, 240, 300, 360, 420, 480, 540, and 600 minutes post-dose
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 7 U Humalog | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) | 649 picomole * hour per liter(pmol*/L) | Geometric Coefficient of Variation 16 |
| 7 U LY900014 | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) | 656 picomole * hour per liter(pmol*/L) | Geometric Coefficient of Variation 17 |
| 15 U Humalog | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) | 1400 picomole * hour per liter(pmol*/L) | Geometric Coefficient of Variation 19 |
| 15 U LY900014 | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) | 1450 picomole * hour per liter(pmol*/L) | Geometric Coefficient of Variation 17 |
| 30 U Humalog | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) | 3050 picomole * hour per liter(pmol*/L) | Geometric Coefficient of Variation 18 |
| 30 U LY900014 | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) | 3180 picomole * hour per liter(pmol*/L) | Geometric Coefficient of Variation 20 |
p-value: 0.549595% CI: [0.974, 1.05]Mixed Models Analysis
p-value: 0.223695% CI: [0.986, 1.06]Mixed Models Analysis
p-value: 0.072795% CI: [0.997, 1.07]Mixed Models Analysis
Secondary
Glucodynamics: Total Amount of Glucose Infused (Gtot)
Glucodynamics: Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp
Time frame: Day 1: Every minute starting from the pre-dose and throughout the duration of the clamp until 10 hours post-dose
Population: All participants who received at least one dose of study drug and completed at least one clamp procedure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 7 U Humalog | Glucodynamics: Total Amount of Glucose Infused (Gtot) | 1120 milligrams per kilogram (mg/kg) | Geometric Coefficient of Variation 53 |
| 7 U LY900014 | Glucodynamics: Total Amount of Glucose Infused (Gtot) | 1080 milligrams per kilogram (mg/kg) | Geometric Coefficient of Variation 60 |
| 15 U Humalog | Glucodynamics: Total Amount of Glucose Infused (Gtot) | 1970 milligrams per kilogram (mg/kg) | Geometric Coefficient of Variation 44 |
| 15 U LY900014 | Glucodynamics: Total Amount of Glucose Infused (Gtot) | 1860 milligrams per kilogram (mg/kg) | Geometric Coefficient of Variation 45 |
| 30 U Humalog | Glucodynamics: Total Amount of Glucose Infused (Gtot) | 3290 milligrams per kilogram (mg/kg) | Geometric Coefficient of Variation 32 |
| 30 U LY900014 | Glucodynamics: Total Amount of Glucose Infused (Gtot) | 3030 milligrams per kilogram (mg/kg) | Geometric Coefficient of Variation 36 |
p-value: 0.574995% CI: [0.87, 1.08]Mixed Models Analysis
p-value: 0.157895% CI: [0.83, 1.03]Mixed Models Analysis
p-value: 0.135195% CI: [0.83, 1.03]Mixed Models Analysis