Healthy
Conditions
Brief summary
The purpose of this study is to compare a study drug known as Insulin glargine with Lantus in healthy Chinese participants. Blood samples will be taken to compare how the body handles the drugs and how they affect blood sugar levels. Side effects and tolerability will be documented. The study will last at least 18 days, not including screening. Screening is required within 4 weeks prior to the start of the study.
Interventions
DRUGInsulin Glargine
Administered SC
DRUGLantus
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Are native Chinese men or women. Native Chinese is defined as a participant who has both parents and all 4 grandparents of Chinese origin. * For females of childbearing potential (defined as not surgically sterilised and between menarche and 1-year postmenopause) only: * Negative serum pregnancy test at the time of screening. * Are not lactating. * Intend not to become pregnant during the study. * Are sexually inactive or have practiced a reliable method of birth control for at least 6 weeks prior to screening. * Agree to continue to use a reliable method of birth control (as determined by the investigator) during the study. * For females not of childbearing potential, must be: * Surgically sterile, defined as having had a hysterectomy or bilateral oophorectomy or tubal ligation, and/or * Menopausal, defined as having had no menses for at least 1 year, or a plasma follicular stimulating hormone value of \>40 milli-international units per milliliter (mIU/mL) and no menses for at least 6 months, unless the participant is taking hormone-replacement therapy. * Having fasting plasma glucose \<110 milligrams per deciliter (mg/dL) (\<6.1 millimoles per liter \[mmol/L\]) and 2-hour glucose level \<140 mg/dL (\<7.8 mmol/L) on the 75 grams (g) oral glucose tolerance test. * Have a body mass index (BMI) between 18 and 28 kilograms per meter squared (kg/m²), inclusive, at screening. * Are nonsmokers, have not smoked for at least 6 months prior to entering the study, and agree not to smoke (cigars, cigarettes, or pipes) or use smokeless tobacco for the duration of the study. * Have normal blood pressure and pulse rate 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 or investigator site, or results with acceptable deviations that are judged to be not clinically significant by the investigator.
Exclusion criteria
* Have a history of first-degree relatives known to have diabetes mellitus. * Have known allergies to insulin glargine or its excipients, or related drugs, or heparin, or have a history of relevant allergic reactions of any origin. * Have a significant history of or current 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; or of interfering with the interpretation of data. * Show evidence of human immunodeficiency virus infection (HIV) and/or positive human HIV antibodies. * Have positive hepatitis B surface antigen. * Have donated \>400 mL of blood in the last 6 months or donated \>100 mL within the last 30 days. * 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 while resident in the clinical research unit (CRU) (1 unit = 12 ounces or 360 mL of beer; 5 ounces or 150 mL of wine; 1.5 ounces or 45 mL of distilled spirits). * Intend to use: prescription medication or over-the-counter medication or Chinese traditional medicine within 14 days before dosing (apart from vitamin/mineral supplements, occasional paracetamol, thyroid replacement, or birth control methods). If this situation arises, an otherwise suitable participant may be included at the discretion of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Insulin Glargine and Lantus | -0.5 and 0 hours predose; 0.5, 1, 2, 3, 4, 6, 9, 12, 15, 18, 21, and 24 hours postdose | Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Insulin glargine and Lantus. |
| PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours (AUC[0-24]) of Insulin Glargine and Lantus | -0.5 and 0 hours predose; 0.5, 1, 2, 3, 4, 6, 9, 12, 15, 18, 21, and 24 hours postdose | PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours (AUC\[0-24\]) of Insulin glargine and Lantus. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamics (PD): Total Amount of Glucose Infused (Gtot) | 30 minutes predose through 24 hours postdose | 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 Insulin glargine or Lantus by adjusting the exogenous glucose infusion rate. Data presented were adjusted by the body weight. |
| PD: Maximum Glucose Infusion Rate (Rmax) | 30 minutes predose through 24 hours postdose | 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 Insulin glargine or Lantus by adjusting the exogenous glucose infusion rate. Data presented were adjusted by the body weight. |
Countries
China
Participant flow
Pre-assignment details
Two period crossover study, with a minimum of 7 days washout period between each period.
Participants by arm
| Arm | Count |
|---|---|
| Overall Participants received 0.5 U/Kg of Insulin glargine and Lantus subcutaneously as per dosing schedule. | 58 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Adverse Event | 0 | 1 |
| Period 1 | Physician Decision | 0 | 1 |
Baseline characteristics
| Characteristic | Overall |
|---|---|
| Age, Continuous | 24.9 years STANDARD_DEVIATION 2.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 58 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 58 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 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 | 0 Participants |
| Region of Enrollment China | 58 Participants |
| Sex: Female, Male Female | 32 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 56 | 0 / 58 |
| other Total, other adverse events | 0 / 56 | 0 / 58 |
| serious Total, serious adverse events | 0 / 56 | 0 / 58 |
Outcome results
Primary
Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Insulin Glargine and Lantus
Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Insulin glargine and Lantus.
Time frame: -0.5 and 0 hours predose; 0.5, 1, 2, 3, 4, 6, 9, 12, 15, 18, 21, and 24 hours postdose
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 U/kg Insulin Glargine | Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Insulin Glargine and Lantus | 124 picomole per liter (pmol/L) | Geometric Coefficient of Variation 31 |
| 0.5 U/kg Lantus | Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Insulin Glargine and Lantus | 129 picomole per liter (pmol/L) | Geometric Coefficient of Variation 33 |
90% CI: [0.886, 1.04]Linear mixed-effects model
Primary
PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours (AUC[0-24]) of Insulin Glargine and Lantus
PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours (AUC\[0-24\]) of Insulin glargine and Lantus.
Time frame: -0.5 and 0 hours predose; 0.5, 1, 2, 3, 4, 6, 9, 12, 15, 18, 21, and 24 hours postdose
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 U/kg Insulin Glargine | PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours (AUC[0-24]) of Insulin Glargine and Lantus | 2170 picomole*hour per liter (pmol*hr/L) | Geometric Coefficient of Variation 28 |
| 0.5 U/kg Lantus | PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours (AUC[0-24]) of Insulin Glargine and Lantus | 2310 picomole*hour per liter (pmol*hr/L) | Geometric Coefficient of Variation 29 |
90% CI: [0.874, 1.02]Linear mixed-effects model
Secondary
PD: 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 Insulin glargine or Lantus by adjusting the exogenous glucose infusion rate. Data presented were adjusted by the body weight.
Time frame: 30 minutes predose through 24 hours postdose
Population: All randomized participants who received at least one dose of study drug and had evaluable Rmax data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 U/kg Insulin Glargine | PD: Maximum Glucose Infusion Rate (Rmax) | 2.72 milligrams/kilograms/minute (mg/kg/min) | Geometric Coefficient of Variation 37 |
| 0.5 U/kg Lantus | PD: Maximum Glucose Infusion Rate (Rmax) | 2.99 milligrams/kilograms/minute (mg/kg/min) | Geometric Coefficient of Variation 36 |
Secondary
Pharmacodynamics (PD): Total Amount of Glucose Infused (Gtot)
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 Insulin glargine or Lantus by adjusting the exogenous glucose infusion rate. Data presented were adjusted by the body weight.
Time frame: 30 minutes predose through 24 hours postdose
Population: All randomized participants who received at least one dose of study drug and had evaluable Gtot data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 U/kg Insulin Glargine | Pharmacodynamics (PD): Total Amount of Glucose Infused (Gtot) | 2390 milligrams/kilogram (mg/kg) | Geometric Coefficient of Variation 43 |
| 0.5 U/kg Lantus | Pharmacodynamics (PD): Total Amount of Glucose Infused (Gtot) | 2680 milligrams/kilogram (mg/kg) | Geometric Coefficient of Variation 40 |