Healthy Volunteers
Conditions
Brief summary
This study involves 2 single injections of LY2963016 and 2 single injections of Lantus. There will be at least 6 days between each injection. The study will compare LY2963016 to Lantus at two different doses. This study is approximately 10 weeks long, not including screening. Screening is required within 4 weeks of the start of the study.
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
* Healthy males or females * Women must be either surgically sterile, post-menopausal, or agree to use a reliable method of birth control during the study * Have a body mass index between 18.5 and 29.9 kilograms per meter squared (kg/m²) * Are nonsmokers and have not smoked for at least 6 months prior to entering the study * Have normal blood pressures and pulse rates at screening, as determined by the investigator * Have an electrocardiogram (ECG) at screening considered as within normal limits by the investigator * Have clinical laboratory test results within normal reference range for the population * Have fasting plasma glucose \<110 milligrams per deciliter (mg/dL) (\<6.0 micromoles per liter \[mmol/L\]) at screening * Have venous access sufficient to allow for blood sampling, intravenous drug administration, and clamp procedures as per the protocol * Have given written informed consent approved by Lilly and the ethical review board (ERB) governing the site
Exclusion criteria
* Are persons who have previously completed or withdrawn from this study * Are currently enrolled in or have discontinued within the last 30 days from a clinical trial involving an investigational drug or device or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study * 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 capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data * Show evidence of significant active neuropsychiatric disease * Show evidence of current use of known drugs of abuse or have a history of use within the past year * Have a history of first-degree relatives known to have diabetes mellitus * Show evidence of an acute infection with fever or infectious disease at the time of study entry * Show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies at screening * Have positive hepatitis B surface antigens at screening * Intend to use over-the-counter medication within 7 days or prescription medication within 14 days prior to dosing (apart from vitamin/mineral supplements, occasional paracetamol, thyroid replacement, or birth control methods) * Have donated blood or had a blood loss of 450 milliliters (mL) 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 48 hours prior to each dosing until discharged from the clinical research unit (CRU)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Area Under the Serum LY2963016 or Lantus Concentration-Time Curve (AUC) From Zero to Infinity [AUC(0-∞)] | Predose up to 24 hours after administration of study drug | Results for LY2936016 treatment arms provide the AUC(0-∞) data for LY2936016, while the results for Lantus treatment arms provide the AUC(0-∞) for Lantus. |
| Pharmacokinetics: Maximum Serum LY2963016 or Lantus Concentration (Cmax) | Predose up to 24 hours after administration of study drug | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Area Under the Serum Concentration-Time Curve From Time Zero to 24 Hours [AUC(0-24)] of LY2963016 or Lantus | Predose up to 24 hours after administration of study drug | Results for LY2936016 treatment arms provide the AUC(0-24) data for LY2936016, while the results for Lantus treatment arms provide the AUC(0-24) for Lantus. |
| Pharmacokinetics: Area Under the Serum Concentration-Time Curve (AUC) From Time Zero to Last Measured Concentration Value [AUC(0-tlast)] of LY2963016 or Lantus | Predose up to 24 hours after administration of study drug | Results for LY2936016 treatment arms provide the AUC(0-tlast) data for LY2936016, while the results for Lantus treatment arms provide the AUC(0-tlast) for Lantus. |
| Maximum Glucose Infusion Rate (Rmax) | Postdose up to 24 hours after administration of study drug | Rmax 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 Lantus by adjusting the exogenous glucose infusion rate. |
| Total Amount of Glucose Infused (Gtot) | Postdose up to 24 hours after administration of study drug | Gtot 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 Lantus by adjusting the exogenous glucose infusion rate. |
Countries
Singapore
Participant flow
Pre-assignment details
This was a 4-treatment, 4-period, crossover, euglycemic clamp study. Participants were randomly assigned to 1 of 4 dosing sequences.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Single subcutaneous dose of 0.3 units/kilogram (U/kg) LY2963016, or 0.6 U/kg LY2963016, or 0.3 U/kg Lantus, or 0.6 U/kg Lantus during 1 of the 4 study periods in 1 of the 4 study sequences. There was a minimum washout interval of 6 days between each period. | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 2 | Adverse Event | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 32.1 years STANDARD_DEVIATION 7.7 |
| Race/Ethnicity, Customized Asian | 24 participants |
| Region of Enrollment Singapore | 24 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 23 | 10 / 24 | 10 / 23 | 12 / 24 |
| serious Total, serious adverse events | 0 / 23 | 0 / 24 | 0 / 23 | 1 / 24 |
Outcome results
Primary
Pharmacokinetics: Area Under the Serum LY2963016 or Lantus Concentration-Time Curve (AUC) From Zero to Infinity [AUC(0-∞)]
Results for LY2936016 treatment arms provide the AUC(0-∞) data for LY2936016, while the results for Lantus treatment arms provide the AUC(0-∞) for Lantus.
Time frame: Predose up to 24 hours after administration of study drug
Population: All participants who received study drug and had sufficient pharmacokinetic data to calculate AUC(0-∞). Participants were analyzed based on the treatment they received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.3 U/kg LY2963016 | Pharmacokinetics: Area Under the Serum LY2963016 or Lantus Concentration-Time Curve (AUC) From Zero to Infinity [AUC(0-∞)] | 2330 picomoles*hour per liter (pmol*h/L) | Geometric Coefficient of Variation 39 |
| 0.6 U/kg LY2963016 | Pharmacokinetics: Area Under the Serum LY2963016 or Lantus Concentration-Time Curve (AUC) From Zero to Infinity [AUC(0-∞)] | 4470 picomoles*hour per liter (pmol*h/L) | Geometric Coefficient of Variation 15 |
| 0.3 U/kg Lantus | Pharmacokinetics: Area Under the Serum LY2963016 or Lantus Concentration-Time Curve (AUC) From Zero to Infinity [AUC(0-∞)] | 2390 picomoles*hour per liter (pmol*h/L) | Geometric Coefficient of Variation 33 |
| 0.6 U/kg Lantus | Pharmacokinetics: Area Under the Serum LY2963016 or Lantus Concentration-Time Curve (AUC) From Zero to Infinity [AUC(0-∞)] | 4310 picomoles*hour per liter (pmol*h/L) | Geometric Coefficient of Variation 51 |
Primary
Pharmacokinetics: Maximum Serum LY2963016 or Lantus Concentration (Cmax)
Time frame: Predose up to 24 hours after administration of study drug
Population: All participants who received study drug and had sufficient pharmacokinetic data to calculate Cmax. Participants were analyzed based on the treatment they received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.3 U/kg LY2963016 | Pharmacokinetics: Maximum Serum LY2963016 or Lantus Concentration (Cmax) | 108 picomoles per liter (pmol/L) | Geometric Coefficient of Variation 20 |
| 0.6 U/kg LY2963016 | Pharmacokinetics: Maximum Serum LY2963016 or Lantus Concentration (Cmax) | 180 picomoles per liter (pmol/L) | Geometric Coefficient of Variation 28 |
| 0.3 U/kg Lantus | Pharmacokinetics: Maximum Serum LY2963016 or Lantus Concentration (Cmax) | 105 picomoles per liter (pmol/L) | Geometric Coefficient of Variation 33 |
| 0.6 U/kg Lantus | Pharmacokinetics: Maximum Serum LY2963016 or Lantus Concentration (Cmax) | 174 picomoles per liter (pmol/L) | Geometric Coefficient of Variation 38 |
Secondary
Maximum Glucose Infusion Rate (Rmax)
Rmax 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 Lantus by adjusting the exogenous glucose infusion rate.
Time frame: Postdose up to 24 hours after administration of study drug
Population: All participants who received study drug and had Rmax measurements. Participants were analyzed based on the treatment they received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.3 U/kg LY2963016 | Maximum Glucose Infusion Rate (Rmax) | 1.81 milligrams/kilograms/minute (mg/kg/min) | Geometric Coefficient of Variation 100 |
| 0.6 U/kg LY2963016 | Maximum Glucose Infusion Rate (Rmax) | 3.05 milligrams/kilograms/minute (mg/kg/min) | Geometric Coefficient of Variation 59 |
| 0.3 U/kg Lantus | Maximum Glucose Infusion Rate (Rmax) | 1.70 milligrams/kilograms/minute (mg/kg/min) | Geometric Coefficient of Variation 92 |
| 0.6 U/kg Lantus | Maximum Glucose Infusion Rate (Rmax) | 3.25 milligrams/kilograms/minute (mg/kg/min) | Geometric Coefficient of Variation 54 |
Secondary
Pharmacokinetics: Area Under the Serum Concentration-Time Curve (AUC) From Time Zero to Last Measured Concentration Value [AUC(0-tlast)] of LY2963016 or Lantus
Results for LY2936016 treatment arms provide the AUC(0-tlast) data for LY2936016, while the results for Lantus treatment arms provide the AUC(0-tlast) for Lantus.
Time frame: Predose up to 24 hours after administration of study drug
Population: All participants who received study drug and had sufficient pharmacokinetic data to calculate AUC(0-tlast). Participants were analyzed based on the treatment they received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.3 U/kg LY2963016 | Pharmacokinetics: Area Under the Serum Concentration-Time Curve (AUC) From Time Zero to Last Measured Concentration Value [AUC(0-tlast)] of LY2963016 or Lantus | 1730 picomoles*hour per liter (pmol*h/L) | Geometric Coefficient of Variation 20 |
| 0.6 U/kg LY2963016 | Pharmacokinetics: Area Under the Serum Concentration-Time Curve (AUC) From Time Zero to Last Measured Concentration Value [AUC(0-tlast)] of LY2963016 or Lantus | 3160 picomoles*hour per liter (pmol*h/L) | Geometric Coefficient of Variation 27 |
| 0.3 U/kg Lantus | Pharmacokinetics: Area Under the Serum Concentration-Time Curve (AUC) From Time Zero to Last Measured Concentration Value [AUC(0-tlast)] of LY2963016 or Lantus | 1670 picomoles*hour per liter (pmol*h/L) | Geometric Coefficient of Variation 28 |
| 0.6 U/kg Lantus | Pharmacokinetics: Area Under the Serum Concentration-Time Curve (AUC) From Time Zero to Last Measured Concentration Value [AUC(0-tlast)] of LY2963016 or Lantus | 2940 picomoles*hour per liter (pmol*h/L) | Geometric Coefficient of Variation 45 |
Secondary
Pharmacokinetics: Area Under the Serum Concentration-Time Curve From Time Zero to 24 Hours [AUC(0-24)] of LY2963016 or Lantus
Results for LY2936016 treatment arms provide the AUC(0-24) data for LY2936016, while the results for Lantus treatment arms provide the AUC(0-24) for Lantus.
Time frame: Predose up to 24 hours after administration of study drug
Population: All participants who received study drug and had sufficient pharmacokinetic data to calculate AUC(0-24). Participants were analyzed based on the treatment they received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.3 U/kg LY2963016 | Pharmacokinetics: Area Under the Serum Concentration-Time Curve From Time Zero to 24 Hours [AUC(0-24)] of LY2963016 or Lantus | 1730 picomoles*hour per liter (pmol*h/L) | Geometric Coefficient of Variation 20 |
| 0.6 U/kg LY2963016 | Pharmacokinetics: Area Under the Serum Concentration-Time Curve From Time Zero to 24 Hours [AUC(0-24)] of LY2963016 or Lantus | 3160 picomoles*hour per liter (pmol*h/L) | Geometric Coefficient of Variation 27 |
| 0.3 U/kg Lantus | Pharmacokinetics: Area Under the Serum Concentration-Time Curve From Time Zero to 24 Hours [AUC(0-24)] of LY2963016 or Lantus | 1690 picomoles*hour per liter (pmol*h/L) | Geometric Coefficient of Variation 30 |
| 0.6 U/kg Lantus | Pharmacokinetics: Area Under the Serum Concentration-Time Curve From Time Zero to 24 Hours [AUC(0-24)] of LY2963016 or Lantus | 2940 picomoles*hour per liter (pmol*h/L) | Geometric Coefficient of Variation 45 |
Secondary
Total Amount of Glucose Infused (Gtot)
Gtot 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 Lantus by adjusting the exogenous glucose infusion rate.
Time frame: Postdose up to 24 hours after administration of study drug
Population: All participants who received study drug and had Gtot measurements. Participants were analyzed based on the treatment they received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.3 U/kg LY2963016 | Total Amount of Glucose Infused (Gtot) | 1060 milligrams per kilograms (mg/kg) | Geometric Coefficient of Variation 178 |
| 0.6 U/kg LY2963016 | Total Amount of Glucose Infused (Gtot) | 2260 milligrams per kilograms (mg/kg) | Geometric Coefficient of Variation 80 |
| 0.3 U/kg Lantus | Total Amount of Glucose Infused (Gtot) | 1050 milligrams per kilograms (mg/kg) | Geometric Coefficient of Variation 130 |
| 0.6 U/kg Lantus | Total Amount of Glucose Infused (Gtot) | 2590 milligrams per kilograms (mg/kg) | Geometric Coefficient of Variation 62 |