Healthy Volunteers
Conditions
Brief summary
The study involves 4 injections of insulin lispro and its purpose is to: * Determine if 2 formulations of insulin lispro are treated by the body in a similar way. * Compare how the 2 formulations of insulin lispro affect blood sugar level. * Determine the safety of each insulin lispro formulations and any side effects that might be associated with them when given to healthy participants. The study is expected to last up to approximately 9 weeks for each participant.
Interventions
BIOLOGICALInsulin Lispro
LY275585 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 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Are healthy males or females * Body mass index (BMI) between 18.5 and 29.9 kilogram per meter squared (kg/m\^2) * Are nonsmokers * Have normal blood pressure and pulse rate, a normal electrocardiogram (ECG), and clinical laboratory test results within normal reference range at screening.
Exclusion criteria
* History of first-degree relatives known to have diabetes mellitus * Evidence of significant active neuropsychiatric disease * Evidence of an acute infection with fever or infectious disease * Intend to use over-the-counter or prescription medication (apart from vitamin/mineral supplements, occasional paracetamol, or birth control methods). * Have used systemic glucocorticoids within 3 months prior to entry into the study. * Have donated blood of 1 unit or more within the last 3 months prior to study entry * Excessive alcohol intake * Have a fasting venous blood glucose (fasting blood glucose \[FBG\], plasma) \>6 millimoles per liter (mmol/L) at screening * Have positive hepatitis B surface antigen.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetic Parameter: Area Under the Serum Insulin Concentration Versus Time Curve From Zero to Time of Return to Baseline (AUC0-tlast) | Day 1, predose through 8 hours post dose in each period. |
| Pharmacokinetic Parameter: Maximum Serum Insulin Concentration (Cmax) | Day 1, predose through 8 hours post dose in each period |
| Pharmacokinetic Parameter: Area Under the Curve(AUC) | Zero to infinity [AUC(0-∞)] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Parameter: Time of Maximum Observed Serum Concentration (Tmax) | Day 1, predose through 8 hours post dose in each period. | — |
| Pharmacodynamic Parameter: Time of Maximum Glucose Infusion Rate (tRmax) | Day 1, predose through 8 hours post dose in each period. | — |
| Pharmacodynamic Parameter: Total Amount of Glucose Infused (Gtot) | Day1, predose through 8 hours post dose in each period. | The total amount of glucose infused during the euglycemic clamp procedure. |
| Pharmacodynamic Parameter: Maximum Glucose Infusion Rate (Rmax) | Day 1, predose through 8 hours post dose in each period. | The maximum observed glucose infusion rate during the euglycemic clamp procedure. |
Countries
Singapore
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Insulin Lispro Dosing Sequence TRTR Each subject was administered insulin lispro A U-200 (test \[T\] on 2 occasions) and insulin lispro B U-100(reference \[R\] on 2 occasions).Subjects were randomly assigned to dosing sequences TRTR. | 19 |
| Insulin Lispro Dosing Sequence RTRT Each subject was administered insulin lispro A U-200 (test \[T\] on 2 occasions) and insulin lispro B U-100 (reference \[R\] on 2 occasions). Subjects were randomly assigned to dosing sequences RTRT. | 19 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Interval Between Dosing (7-8 Days) | Adverse Event | 1 | 1 |
Baseline characteristics
| Characteristic | Insulin Lispro Dosing Sequence TRTR | Insulin Lispro Dosing Sequence RTRT | Total |
|---|---|---|---|
| Age, Continuous | 32.9 years STANDARD_DEVIATION 6.1 | 30.4 years STANDARD_DEVIATION 8.2 | 31.7 years STANDARD_DEVIATION 7.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 19 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Singapore | 19 participants | 19 participants | 38 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 17 Participants | 18 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 21 / 38 | 16 / 38 |
| serious Total, serious adverse events | 0 / 38 | 0 / 38 |
Outcome results
Primary
Pharmacokinetic Parameter: Area Under the Curve(AUC)
Time frame: Zero to infinity [AUC(0-∞)]
Population: All participants who had at least one study treatment and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro A | Pharmacokinetic Parameter: Area Under the Curve(AUC) | 2330 picomole*hour/liter (pmol*h/L) | Geometric Coefficient of Variation 15 |
| Insulin Lispro B | Pharmacokinetic Parameter: Area Under the Curve(AUC) | 2360 picomole*hour/liter (pmol*h/L) | Geometric Coefficient of Variation 16 |
90% CI: [0.975, 1.01]
Primary
Pharmacokinetic Parameter: Area Under the Serum Insulin Concentration Versus Time Curve From Zero to Time of Return to Baseline (AUC0-tlast)
Time frame: Day 1, predose through 8 hours post dose in each period.
Population: All participants who had at least one study treatment and had evaluable pharmacokinetic (PK) data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro A | Pharmacokinetic Parameter: Area Under the Serum Insulin Concentration Versus Time Curve From Zero to Time of Return to Baseline (AUC0-tlast) | 2200 picomole*hour/liter (pmol*h/L) | Geometric Coefficient of Variation 16 |
| Insulin Lispro B | Pharmacokinetic Parameter: Area Under the Serum Insulin Concentration Versus Time Curve From Zero to Time of Return to Baseline (AUC0-tlast) | 2230 picomole*hour/liter (pmol*h/L) | Geometric Coefficient of Variation 17 |
90% CI: [0.965, 1.01]
Primary
Pharmacokinetic Parameter: Maximum Serum Insulin Concentration (Cmax)
Time frame: Day 1, predose through 8 hours post dose in each period
Population: All participants who had at least one study treatment and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro A | Pharmacokinetic Parameter: Maximum Serum Insulin Concentration (Cmax) | 744 picomole/liter (pmol/L) | Geometric Coefficient of Variation 38 |
| Insulin Lispro B | Pharmacokinetic Parameter: Maximum Serum Insulin Concentration (Cmax) | 851 picomole/liter (pmol/L) | Geometric Coefficient of Variation 38 |
90% CI: [0.828, 0.919]
Secondary
Pharmacodynamic Parameter: Maximum Glucose Infusion Rate (Rmax)
The maximum observed glucose infusion rate during the euglycemic clamp procedure.
Time frame: Day 1, predose through 8 hours post dose in each period.
Population: All participants who had at least one study treatment and had evaluable PD data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro A | Pharmacodynamic Parameter: Maximum Glucose Infusion Rate (Rmax) | 503 milligrams per minute (mg/min) | Geometric Coefficient of Variation 36 |
| Insulin Lispro B | Pharmacodynamic Parameter: Maximum Glucose Infusion Rate (Rmax) | 526 milligrams per minute (mg/min) | Geometric Coefficient of Variation 36 |
90% CI: [0.901, 1]
Secondary
Pharmacodynamic Parameter: Time of Maximum Glucose Infusion Rate (tRmax)
Time frame: Day 1, predose through 8 hours post dose in each period.
Population: All participants who had at least one study treatment and had evaluable PD data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro A | Pharmacodynamic Parameter: Time of Maximum Glucose Infusion Rate (tRmax) | 2.71 hours | Geometric Coefficient of Variation 52 |
| Insulin Lispro B | Pharmacodynamic Parameter: Time of Maximum Glucose Infusion Rate (tRmax) | 2.32 hours | Geometric Coefficient of Variation 52 |
90% CI: [0.164, 0.685]
Secondary
Pharmacodynamic Parameter: Total Amount of Glucose Infused (Gtot)
The total amount of glucose infused during the euglycemic clamp procedure.
Time frame: Day1, predose through 8 hours post dose in each period.
Population: All participants who had at least one study treatment and had evaluable pharmacodynamic(PD) data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro A | Pharmacodynamic Parameter: Total Amount of Glucose Infused (Gtot) | 120 grams (g) | Geometric Coefficient of Variation 31 |
| Insulin Lispro B | Pharmacodynamic Parameter: Total Amount of Glucose Infused (Gtot) | 120 grams (g) | Geometric Coefficient of Variation 33 |
90% CI: [0.954, 1.02]
Secondary
Pharmacokinetic Parameter: Time of Maximum Observed Serum Concentration (Tmax)
Time frame: Day 1, predose through 8 hours post dose in each period.
Population: All participants who had at least one study treatment and had evaluable PK data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Insulin Lispro A | Pharmacokinetic Parameter: Time of Maximum Observed Serum Concentration (Tmax) | 1 hours |
| Insulin Lispro B | Pharmacokinetic Parameter: Time of Maximum Observed Serum Concentration (Tmax) | 1 hours |
90% CI: [0, 0.375]