Diabetes Mellitus
Conditions
Brief summary
The purposes of this study are to determine the pharmacokinetics and pharmacodynamics of LY2963016 compared to those of basal insulin. The study will also gather information on the safety and tolerability of LY2963016 in healthy participants. Each study period will be approximately 8.5 days (1.5 days for treatment and 7 day washout period). There are 4 study periods.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* are overtly healthy males or females, as determined by medical history and physical examination * male participants: agree to use a reliable method of birth control during the study. * female participants of child-bearing potential must test negative for pregnancy at the time of enrollment and agree to either abstain from sexual activity or to use a medically accepted means of contraception when engaging in sexual intercourse throughout the study, or female participants not of child-bearing potential due to surgical sterilization or menopause * have a body weight of at least 55 kilograms (kg), and body mass index (BMI) of 18.5 to 32.0 kilograms/square meter (kg/m²) * have clinical laboratory test results within normal reference range for the population * have venous access sufficient to allow for blood sampling * are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures * have given written informed consent * participants should have a normal oral glucose tolerance test
Exclusion criteria
* are currently enrolled in, have completed or discontinued within the last 30 days from, a clinical trial involving an investigational product other than the investigational product used in this study; 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 heparin, insulin glargine, related compounds or any components of the formulation * are persons who have previously received the investigational product in this study, have completed or withdrawn from this study or any other study investigating LY2963016 * have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study * have an abnormal blood pressure as determined by the investigator * have a significant history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, haematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication * show evidence of significant active neuropsychiatric disease * regularly use known drugs of abuse and/or show positive findings on urinary drug screening * show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies * show evidence of hepatitis C and/or positive hepatitis C antibody * show evidence of hepatitis B and/or positive hepatitis B surface antigen * are women with a positive pregnancy test or women who are lactating * intend to use over-the-counter or prescription medication * have donated blood of more than 500 milliliters (mL) within the last 56 days before dosing of Period 1 * 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 for 24 hours before dosing and throughout the duration of each study period * smoke more than 10 cigarettes (or equivalent other tobacco products) per day * have a fasting blood glucose \> 5.5 millimoles/Liter (mmol/L) \[\>99 milligrams/deciliter (mg/dL)\]at screening * have a positive test for anti-LY2963016 or anti-glargine antibodies
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to 24 Hours [AUC(0-24)] of LY2963016 and Lantus | 1 hour predose up to 24 hours postdose in all treatment periods |
| Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2963016 and Lantus | 1 hour predose up to 24 hours postdose in all treatment periods |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Glucose Infusion Rate (Rmax) | 1 hour 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 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 | 1 hour predose up to 24 hours postdose in all treatment periods | Gtot is the total glucose infusion over the clamp duration 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 Lantus by adjusting the exogenous glucose infusion rate. Data presented were adjusted by the body weight. |
Countries
South Africa
Participant flow
Pre-assignment details
This was a randomized, 2-sequence, 4-period, crossover study.
Participants by arm
| Arm | Count |
|---|---|
| All Participants A single 0.5 units/kilogram (U/kg) dose of LY2963016 or a single 0.5 U/kg dose of Lantus administered subcutaneously followed by minimum washout interval of 7 days during 2 of 4 study periods in each sequence. | 80 |
| Total | 80 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 32.0 years STANDARD_DEVIATION 10.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants |
| Race (NIH/OMB) More than one race | 6 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 | 64 Participants |
| Region of Enrollment South Africa | 80 participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 50 / 80 | 54 / 80 |
| serious Total, serious adverse events | 0 / 80 | 0 / 80 |
Outcome results
Primary
Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to 24 Hours [AUC(0-24)] of LY2963016 and Lantus
Time frame: 1 hour predose up to 24 hours postdose in all treatment periods
Population: All randomized participants who received at least 1 dose of study drug and had evaluable pharmacokinetic data to calculate AUC(0-24). Participants were analyzed based on the treatment they received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2963016 | Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to 24 Hours [AUC(0-24)] of LY2963016 and Lantus | 1810 picomoles*hour/Liter (pmol*h/L) | Geometric Coefficient of Variation 40 |
| Lantus | Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to 24 Hours [AUC(0-24)] of LY2963016 and Lantus | 1980 picomoles*hour/Liter (pmol*h/L) | Geometric Coefficient of Variation 36 |
Primary
Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2963016 and Lantus
Time frame: 1 hour predose up to 24 hours postdose in all treatment periods
Population: All randomized participants who received at least 1 dose of study drug and had evaluable pharmacokinetic data to calculate Cmax. Participants were analyzed based on the treatment they received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2963016 | Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2963016 and Lantus | 112 picomoles/Liter (pmol/L) | Geometric Coefficient of Variation 39 |
| Lantus | Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2963016 and Lantus | 119 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 Lantus by adjusting the exogenous glucose infusion rate. Data presented were adjusted by the body weight.
Time frame: 1 hour predose up to 24 hours postdose in all treatment periods
Population: All randomized participants who received at least 1 dose of study drug and had evaluable 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) | 2.85 milligrams/kilogram/minute (mg/kg/min) | Geometric Coefficient of Variation 46 |
| Lantus | Maximum Glucose Infusion Rate (Rmax) | 2.88 milligrams/kilogram/minute (mg/kg/min) | Geometric Coefficient of Variation 41 |
Secondary
Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp Procedure
Gtot is the total glucose infusion over the clamp duration 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 Lantus by adjusting the exogenous glucose infusion rate. Data presented were adjusted by the body weight.
Time frame: 1 hour predose up to 24 hours postdose in all treatment periods
Population: All randomized participants who received at least 1 dose of study drug and had evaluable 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 | 2580 milligrams/kilogram (mg/kg) | Geometric Coefficient of Variation 45 |
| Lantus | Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp Procedure | 2710 milligrams/kilogram (mg/kg) | Geometric Coefficient of Variation 40 |