Diabetes Mellitus, Type 1
Conditions
Brief summary
This study will compare LY900014, a drug that lowers blood sugar, with insulin lispro (Humalog). Both drugs will be given by injection under the skin of the abdomen. This study will be conducted in participants with type 1 diabetes to investigate how quickly and how much LY900014 is absorbed and the effect of LY900014 on blood sugar levels in comparison with insulin lispro. The study will last about 3 to 6 weeks for each participant, not including screening.
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Are Japanese male or female participant with a diagnosis of T1DM, based on the World Health Organization classification, for at least 1 year prior to screening * Have a body mass index (BMI) of 18.5 to 30.0 kilograms per square meter (kg/m²) * Have a glycated hemoglobin \<9.0% at screening
Exclusion criteria
* Have, except for current regimen of insulin therapy and concomitant medication(s), regular use of or intended use of any over-the-counter or prescription medications or nutritional supplements that treat hyperglycemia or insulin resistance or that promote weight loss within 14 days before dosing * Are receiving chronic (lasting longer than 14 consecutive days) systemic or inhaled glucocorticoid therapy (excluding topical, intra-articular, and intraocular preparations), or have received such therapy within the 4 weeks before screening * Have a history of renal impairment (exclusion only if estimated glomerular filtration rate \[GFR\] \<60 milliliters/minute/1.73 square meters \[GFR is estimated according to a formula recommended by the Japanese Society of Nephrology\]), or have a serum creatinine level ≥126 micromoles per liter (μmol/L) (\>1.42 milligrams per deciliter \[mg/dL\]) (male) or ≥111 μmol/L (\>1.25 mg/dL) (female) * Have a history of deep vein thrombosis of the leg, or repeated episodes of deep leg vein thrombosis in first-degree relatives (parents, siblings, or children), as determined by the investigator * Have proliferative retinopathy or maculopathy and/or severe neuropathy; in particular, autonomic neuropathy, as determined by the investigator based on a recent (\<1.5 years) ophthalmologic examination * Have had any significant changes in insulin regimen and/or unstable blood glucose control within the past 3 months prior to screening, as determined by the investigator * Require daily insulin treatment \>1.5 units per kilogram (U/kg)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve Zero to 10 Hours (AUC 0-10h) Following Administration of Each Treatment Arm | Predose, 5 minutes (min), 10 min, 15 min, 20 min, 25 min, 30 min, 35 min, 40 min, 45 min, 50 min, 55 min, 60 min, 70 min, 90 min, 120 min, 150 min, 180 min, 240 min, 300 min, 360 min, 420 min, 480 min, 540 min, and 600 min postdose | PK: Insulin Lispro AUC from time zero to 10 hours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glucodynamics (GD): Total Amount of Glucose Infused (Gtot) Over Duration of Clamp Following Administration of Each Treatment Arm | Predose, every minute from run-in and for the duration of the EC until up to 10 hours postdose | Gtot Over Duration of Clamp for Each Treatment Arm. 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 (EC) procedure. During the euglycemic clamp procedure, blood glucose concentrations are held constant after the administration of study treatment by adjusting the exogenous glucose infusion rate. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants All randomized participants who received at least 1 dose of study drug. | 31 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 2 | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 39.5 years STANDARD_DEVIATION 11.3 |
| Body Mass Index | 22.85 kilograms per meter squared STANDARD_DEVIATION 2.44 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 161.35 centimeters STANDARD_DEVIATION 7.44 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 31 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 Japan | 31 Participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 13 Participants |
| Weight | 59.62 kilograms STANDARD_DEVIATION 8.29 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 30 |
| other Total, other adverse events | 6 / 31 | 7 / 30 |
| serious Total, serious adverse events | 0 / 31 | 0 / 30 |
Outcome results
Primary
Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve Zero to 10 Hours (AUC 0-10h) Following Administration of Each Treatment Arm
PK: Insulin Lispro AUC from time zero to 10 hours
Time frame: Predose, 5 minutes (min), 10 min, 15 min, 20 min, 25 min, 30 min, 35 min, 40 min, 45 min, 50 min, 55 min, 60 min, 70 min, 90 min, 120 min, 150 min, 180 min, 240 min, 300 min, 360 min, 420 min, 480 min, 540 min, and 600 min postdose
Population: All randomized participants who received at least 1 dose of study drug and had evaluable PK parameters.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 15 U LY900014 | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve Zero to 10 Hours (AUC 0-10h) Following Administration of Each Treatment Arm | 1930 picomols times hour per Liter | Geometric Coefficient of Variation 59 |
| 15 U Insulin Lispro (Humalog) | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve Zero to 10 Hours (AUC 0-10h) Following Administration of Each Treatment Arm | 1980 picomols times hour per Liter | Geometric Coefficient of Variation 20 |
95% CI: [0.803, 1.17]
Secondary
Glucodynamics (GD): Total Amount of Glucose Infused (Gtot) Over Duration of Clamp Following Administration of Each Treatment Arm
Gtot Over Duration of Clamp for Each Treatment Arm. 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 (EC) procedure. During the euglycemic clamp procedure, blood glucose concentrations are held constant after the administration of study treatment by adjusting the exogenous glucose infusion rate.
Time frame: Predose, every minute from run-in and for the duration of the EC until up to 10 hours postdose
Population: All randomized participants who received at least 1 dose of study drug and had evaluable GD data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 15 U LY900014 | Glucodynamics (GD): Total Amount of Glucose Infused (Gtot) Over Duration of Clamp Following Administration of Each Treatment Arm | 1190 milligrams per kilogram | Geometric Coefficient of Variation 54 |
| 15 U Insulin Lispro (Humalog) | Glucodynamics (GD): Total Amount of Glucose Infused (Gtot) Over Duration of Clamp Following Administration of Each Treatment Arm | 1250 milligrams per kilogram | Geometric Coefficient of Variation 34 |