Healthy Volunteers
Conditions
Keywords
insulin, lispro
Brief summary
This study will compare how the body treats 2 different forms of insulin lispro and how they affect blood sugar levels.
Detailed description
The 2 formulations of insulin lispro will be referred to here as: Lispro A Lispro B
Interventions
DRUGInsulin lispro A
20 units (U) subcutaneously (SC).
DRUGInsulin lispro B
20 U subcutaneously (SC).
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Are healthy males or females. * Body mass index (BMI) between 18.5 and 29.9 kilograms 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 (FBG, plasma) \>6 millimoles/liter (mmol/L) at screening. * Have positive hepatitis B surface antigen.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Parameter: Area Under the Serum Insulin Concentration Versus Time Curve From Time Zero to the Last Time Point With a Measurable Concentration [AUC0-tlast] | 0 up to 8 hours post dose | Primary outcome measure is based on the pharmacokinetic area under the concentration-time curve from time 0 to the last time point with a measurable concentration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Parameter: Maximum Serum Insulin Concentration [Cmax] | 0 to 8 hours post dose | The maximum observed insulin lispro concentration following dosing. |
| Pharmacodynamic Parameter: Maximum Glucose Infusion Rate (Rmax) | 0 to 8 hours post dose | The maximum observed glucose infusion rate during the euglycemic clamp procedure. |
| Pharmacodynamic Parameter: Time of Maximum Glucose Infusion Rate (tRmax) | 0 to 8 hours post dose | Time of maximal glucose infusion rate. |
| Pharmacodynamic Parameter: Total Amount of Glucose Infused (Gtot) | 0 to 8 hours post dose | The total amount of glucose infused during the euglycemic clamp procedure. |
Countries
Singapore
Participant flow
Pre-assignment details
41 participants were enrolled into the study. 3 participants discontinued due to subject decision prior to receiving treatment.
Participants by arm
| Arm | Count |
|---|---|
| Insulin Lispro Dosing Sequence ABAB Each participant was administered insulin lispro A formulation (Treatment A, test - 2 occasions) and insulin lispro B formulation (Treatment B, reference - 2 occasions) in the dosing sequence ABAB. | 20 |
| Insulin Lispro Dosing Sequence BABA Each participant was administered insulin lispro A formulation (Treatment A, test - 2 occasions) and insulin lispro B formulation (Treatment B, reference - 2 occasions) in the dosing sequence BABA. | 18 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Interval Between Dosing (4-7 Days) | Protocol Violation | 0 | 1 |
| Interval Between Dosing (4-7 Days) | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Insulin Lispro Dosing Sequence ABAB | Insulin Lispro Dosing Sequence BABA | Total |
|---|---|---|---|
| Age, Continuous | 30.4 years STANDARD_DEVIATION 7.2 | 34.6 years STANDARD_DEVIATION 6.4 | 32.4 years STANDARD_DEVIATION 7.1 |
| Race/Ethnicity, Customized Hispanic or Latino | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 20 participants | 18 participants | 38 participants |
| Region of Enrollment Singapore | 20 participants | 18 participants | 38 participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 20 Participants | 16 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 37 | 12 / 38 |
| serious Total, serious adverse events | 0 / 37 | 0 / 38 |
Outcome results
Primary
Pharmacokinetic Parameter: Area Under the Serum Insulin Concentration Versus Time Curve From Time Zero to the Last Time Point With a Measurable Concentration [AUC0-tlast]
Primary outcome measure is based on the pharmacokinetic area under the concentration-time curve from time 0 to the last time point with a measurable concentration.
Time frame: 0 up to 8 hours post dose
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 Time Zero to the Last Time Point With a Measurable Concentration [AUC0-tlast] | 1920 picomole*hour/liter (pmol*h/L) | Geometric Coefficient of Variation 20 |
| Insulin Lispro B | Pharmacokinetic Parameter: Area Under the Serum Insulin Concentration Versus Time Curve From Time Zero to the Last Time Point With a Measurable Concentration [AUC0-tlast] | 1940 picomole*hour/liter (pmol*h/L) | Geometric Coefficient of Variation 20 |
90% CI: [0.948, 1.034]
Secondary
Pharmacodynamic Parameter: Maximum Glucose Infusion Rate (Rmax)
The maximum observed glucose infusion rate during the euglycemic clamp procedure.
Time frame: 0 to 8 hours post dose
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: Maximum Glucose Infusion Rate (Rmax) | 544 milligrams per minute (mg/min) | Geometric Coefficient of Variation 23 |
| Insulin Lispro B | Pharmacodynamic Parameter: Maximum Glucose Infusion Rate (Rmax) | 539 milligrams per minute (mg/min) | Geometric Coefficient of Variation 27 |
90% CI: [0.958, 1.054]
Secondary
Pharmacodynamic Parameter: Time of Maximum Glucose Infusion Rate (tRmax)
Time of maximal glucose infusion rate.
Time frame: 0 to 8 hours post dose
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) | 2.11 hours | Geometric Coefficient of Variation 49 |
| Insulin Lispro B | Pharmacodynamic Parameter: Time of Maximum Glucose Infusion Rate (tRmax) | 2.00 hours | Geometric Coefficient of Variation 56 |
90% CI: [-0.4, 0.5]
Secondary
Pharmacodynamic Parameter: Total Amount of Glucose Infused (Gtot)
The total amount of glucose infused during the euglycemic clamp procedure.
Time frame: 0 to 8 hours post dose
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: Total Amount of Glucose Infused (Gtot) | 125 grams (g) | Geometric Coefficient of Variation 25 |
| Insulin Lispro B | Pharmacodynamic Parameter: Total Amount of Glucose Infused (Gtot) | 123 grams (g) | Geometric Coefficient of Variation 30 |
90% CI: [0.961, 1.07]
Secondary
Pharmacokinetic Parameter: Maximum Serum Insulin Concentration [Cmax]
The maximum observed insulin lispro concentration following dosing.
Time frame: 0 to 8 hours post dose
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] | 819 picomole/liter (pmol/L) | Geometric Coefficient of Variation 32 |
| Insulin Lispro B | Pharmacokinetic Parameter: Maximum Serum Insulin Concentration [Cmax] | 887 picomole/liter (pmol/L) | Geometric Coefficient of Variation 34 |
90% CI: [0.897, 0.972]