Healthy
Conditions
Keywords
Volunteers
Brief summary
The purpose of this study is to compare the pharmacokinetics and pharmacodynamics of LY2963016 and US-approved Lantus®. The study involves four single injections; two doses of LY2963016 and two doses of US-approved Lantus®. The study will have 4 periods. In each period, a single injection will be administered before undergoing a euglycemic clamp that lasts for 24 hours. There will be at least a 7 day washout between each period. Side effects will be documented. Study participation is expected to last up to 14 weeks.
Interventions
DRUGLY2963016
Administered subcutaneously
DRUGUS Approved Lantus
Administered subcutaneously
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
21 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Are overtly healthy males or females * Have body mass index between 18.5 and 29.9 kilograms per meter square (kg/m\^2) * Are nonsmokers and have not smoked for at least 2 months prior to entering the study * Have normal blood pressure and pulse rates at screening * Have electrocardiograms (ECGs) at screening considered as within normal limits * Have clinical laboratory test results within normal reference ranges
Exclusion criteria
* Are currently enrolled in or discontinued within the last 30 days from a clinical study involving an investigational drug or device or are concurrently enrolled in any other type of medical research * Have known allergies to insulin, its excipients, or related drugs or have history of relevant allergic reactions of any origin * Have significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders * Show evidence of significant active neuropsychiatric disease, including taking prescription medication for such diseases * Show evidence of current use of known drugs of abuse or a history of use within the past year * Have a history of first-degree relatives known to have diabetes mellitus * Show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies at screening * Have positive hepatitis B surface antigen at screening * Intend to use over-the-counter or prescription medication within 7 or 14 days, respectively, prior to dosing (apart from vitamin/mineral supplements, occasional paracetamol, thyroid replacement medication, or birth control methods) * Have donated or had a blood loss of 450 milliliters (mL) within 3 months prior to study enrollment * Have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females) or are unwilling to stop alcohol consumption from 24 hours prior to each dosing until discharged from the clinical research unit (CRU)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY2963016 and US-Approved Lantus | 30 minutes predose up to 24 hours postdose in all treatment periods | The AUC from time 0 to 24 hours (AUC0-24) of LY2963016 and US-Approved Lantus was measured. |
| Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of LY2963016 and US-Approved Lantus | 30 minutes predose up to 24 hours postdose in all treatment periods | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Glucose Infusion Rate (Rmax) | 30 minutes predose up to 24 hours postdose in all treatment periods | Rmax is the maximum infusion rate of glucose administered intravenously needed to maintain target blood glucose level and is used to measure the study drug action over time as measured by the euglycaemic clamp procedure. During the euglycaemic clamp procedure, blood glucose concentrations are held constant after the administration of LY2963016 or US-approved Lantus by adjusting the exogenous glucose infusion rate. Data presented were adjusted by the body weight. |
| Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp Procedure | 30 minutes predose up to 24 hours postdose in all treatment periods | Gtot was the total glucose infusion over the clamp duration and was used to measure the study drug action over time as measured by the euglycaemic clamp procedure. During the euglycaemic clamp procedure, blood glucose concentrations were held constant after the administration of LY2963016 or US-approved Lantus by adjusting the exogenous glucose infusion rate. Data presented were adjusted by the body weight. |
Countries
Singapore
Participant flow
Pre-assignment details
The study comprised 2 sequences with 4 treatment periods. Participants were randomly assigned to 1 of the 2 sequences.
Participants by arm
| Arm | Count |
|---|---|
| LY2963016 and US-approved Lantus Single 0.5-units per kilogram (U/kg) dose of LY2963016 administered subcutaneously twice during the study; Single 0.5-U/kg dose of US-approved Lantus administered subcutaneously twice during the study. There was at least a 7-day washout between treatment periods. | 91 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout 1 | Adverse Event | 0 | 1 |
| Washout 1 | Physician Decision | 0 | 1 |
| Washout 1 | Withdrawal by Subject | 1 | 0 |
| Washout 2 | Physician Decision | 1 | 0 |
| Washout 2 | Sponsor Decision | 1 | 2 |
| Washout 2 | Withdrawal by Subject | 1 | 0 |
| Washout 3 | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | LY2963016 and US-approved Lantus |
|---|---|
| Age, Continuous | 32.7 years STANDARD_DEVIATION 9 |
| Race/Ethnicity, Customized Asian | 90 participants |
| Race/Ethnicity, Customized White | 1 participants |
| Region of Enrollment Singapore | 91 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 85 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 42 / 89 | 42 / 90 |
| serious Total, serious adverse events | 0 / 89 | 0 / 90 |
Outcome results
Primary
Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY2963016 and US-Approved Lantus
The AUC from time 0 to 24 hours (AUC0-24) of LY2963016 and US-Approved Lantus was measured.
Time frame: 30 minutes predose up to 24 hours postdose in all treatment periods
Population: Full analysis set (FAS): All randomized participants who received at least 1 dose of study drug and had evaluable PK data to calculate AUC(0-24). Participants were analyzed based on the treatment they received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2963016 | Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY2963016 and US-Approved Lantus | 1720 picomoles*hour/liter (pmol*h/L) | Geometric Coefficient of Variation 42 |
| US-approved Lantus | Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY2963016 and US-Approved Lantus | 1900 picomoles*hour/liter (pmol*h/L) | Geometric Coefficient of Variation 35 |
Primary
Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of LY2963016 and US-Approved Lantus
Time frame: 30 minutes predose up to 24 hours postdose in all treatment periods
Population: Full analysis set (FAS): All randomized participants who received at least 1 dose of study drug and had evaluable PK data to calculate Cmax. Participants were analyzed based on the treatment they received
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2963016 | Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of LY2963016 and US-Approved Lantus | 103 picomoles/liter (pmol/L) | Geometric Coefficient of Variation 41 |
| US-approved Lantus | Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of LY2963016 and US-Approved Lantus | 111 picomoles/liter (pmol/L) | Geometric Coefficient of Variation 34 |
Secondary
Maximum Glucose Infusion Rate (Rmax)
Rmax is the maximum infusion rate of glucose administered intravenously needed to maintain target blood glucose level and is used to measure the study drug action over time as measured by the euglycaemic clamp procedure. During the euglycaemic clamp procedure, blood glucose concentrations are held constant after the administration of LY2963016 or US-approved Lantus by adjusting the exogenous glucose infusion rate. Data presented were adjusted by the body weight.
Time frame: 30 minutes predose up to 24 hours postdose in all treatment periods
Population: Full analysis set (FAS): All randomized participants who received at least 1 dose of study drug and had evaluable pharmacodynamic data to calculate Rmax. Participants were analyzed based on the treatment they received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2963016 | Maximum Glucose Infusion Rate (Rmax) | 2.12 milligrams/kilograms/minute (mg/kg/min) | Geometric Coefficient of Variation 54 |
| US-approved Lantus | Maximum Glucose Infusion Rate (Rmax) | 2.27 milligrams/kilograms/minute (mg/kg/min) | Geometric Coefficient of Variation 58 |
Secondary
Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp Procedure
Gtot was the total glucose infusion over the clamp duration and was used to measure the study drug action over time as measured by the euglycaemic clamp procedure. During the euglycaemic clamp procedure, blood glucose concentrations were held constant after the administration of LY2963016 or US-approved Lantus by adjusting the exogenous glucose infusion rate. Data presented were adjusted by the body weight.
Time frame: 30 minutes predose up to 24 hours postdose in all treatment periods
Population: Full analysis set (FAS): All randomized participants who received at least 1 dose of study drug and had evaluable pharmacodynamic data to calculate Gtot. Participants were analyzed based on the treatment they received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2963016 | Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp Procedure | 1670 milligrams/kilogram (mg/kg) | Geometric Coefficient of Variation 60 |
| US-approved Lantus | Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp Procedure | 1820 milligrams/kilogram (mg/kg) | Geometric Coefficient of Variation 74 |