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 subjects. The study is approximately 12 weeks.
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 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Are overtly healthy males or females * Have a body mass index (BMI) between 18.5 and 29.9 kilogram per square meter (kg/m\^2) * Are nonsmokers * Have normal blood pressure and pulse rate * Have an electrocardiogram (ECG) considered as within normal limits * Have clinical laboratory test results within normal reference range
Exclusion criteria
* Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device * Have known allergies to insulin or its excipients * Have significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders * Show evidence of significant active neuropsychiatric disease * Have a history of first-degree relatives known to have diabetes mellitus * Have a fasting venous blood glucose \>6.0 millimoles per liter (mmol/L) * Intend to use over-the-counter or prescription medication * Have donated or had a blood loss of 450 milliliters (mL) or more in the past 3 months * Have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) | Periods 1 and 2: Baseline up to 24 hours | AUC from time zero to 24 hours (AUC0-24) is reported for this outcome measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Maximum Concentration (Cmax) | Periods 1 and 2: Baseline up to 24 hours | — |
| Maximum Glucose Infusion Rate (Rmax) | Periods 1 and 2: Baseline up to 24 hours | — |
| Total Glucose Infused (Gtot) | Periods 1 and 2: Baseline up to 24 hours | — |
| Time of Maximum Glucose Infusion Rate (tRmax) | Periods 1 and 2: Baseline up to 24 hours | — |
| Number of Participants With Clinically Significant Effects | Baseline up to 30 days | Clinically significant effects were defined as serious and nonserious adverse events. A summary of serious and all other nonserious adverse events is located in the Reported Adverse Event module. |
Countries
Singapore
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population For the LY2963016 first, then Lantus group: A single 0.5-unit per kilogram (U/kg) dose of LY2963016 was administered subcutaneously during Period 1 (1 period=24 hours), followed by a washout period of at least 7 days before a single 0.5-U/kg Lantus dose was administered subcutaneously during Period 2 (1 period=24 hours).
For the Lantus first, then LY2963016 group: A single 0.5-U/kg dose of Lantus was administered subcutaneously during Period 1 (1 period=24 hours), followed by a washout period of at least 7 days before a single 0.5-U/kg dose of LY2963016 was administered subcutaneously during Period 2 (1 period=24 hours). | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 2 (up to 24 Hours After Dosing) | Adverse Event | 2 | 0 |
| Washout Period of at Least 7 Days | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Continuous | 31.1 years STANDARD_DEVIATION 7.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 14 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 | 2 Participants |
| Region of Enrollment Singapore | 16 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 16 | 6 / 13 |
| serious Total, serious adverse events | 0 / 16 | 0 / 13 |
Outcome results
Primary
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC)
AUC from time zero to 24 hours (AUC0-24) is reported for this outcome measure.
Time frame: Periods 1 and 2: Baseline up to 24 hours
Population: All randomized participants who received at least 1 dose of study drug, completed at least 1 clamp procedure, and had evaluable pharmacokinetic data were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2963016 | Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) | 1900 picomole*hour per liter (pmol*hr/L) | Geometric Coefficient of Variation 22 |
| Lantus | Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) | 2180 picomole*hour per liter (pmol*hr/L) | Geometric Coefficient of Variation 30 |
Secondary
Maximum Glucose Infusion Rate (Rmax)
Time frame: Periods 1 and 2: Baseline up to 24 hours
Population: All randomized participants who received at least 1 dose of study drug, completed at least 1 clamp procedure, and had evaluable glucodynamic data were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2963016 | Maximum Glucose Infusion Rate (Rmax) | 10.2 grams per hour (g/h) | Geometric Coefficient of Variation 50 |
| Lantus | Maximum Glucose Infusion Rate (Rmax) | 11.3 grams per hour (g/h) | Geometric Coefficient of Variation 32 |
Secondary
Number of Participants With Clinically Significant Effects
Clinically significant effects were defined as serious and nonserious adverse events. A summary of serious and all other nonserious adverse events is located in the Reported Adverse Event module.
Time frame: Baseline up to 30 days
Population: All randomized participants were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LY2963016 | Number of Participants With Clinically Significant Effects | Serious Adverse Events | 0 participants |
| LY2963016 | Number of Participants With Clinically Significant Effects | Nonserious Adverse Events | 8 participants |
| Lantus | Number of Participants With Clinically Significant Effects | Serious Adverse Events | 0 participants |
| Lantus | Number of Participants With Clinically Significant Effects | Nonserious Adverse Events | 6 participants |
Secondary
Pharmacokinetics: Maximum Concentration (Cmax)
Time frame: Periods 1 and 2: Baseline up to 24 hours
Population: All randomized participants who received at least 1 dose of study drug, completed at least 1 clamp procedure, and had evaluable pharmacokinetic data were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2963016 | Pharmacokinetics: Maximum Concentration (Cmax) | 110 picomole per liter (pmol/L) | Geometric Coefficient of Variation 26 |
| Lantus | Pharmacokinetics: Maximum Concentration (Cmax) | 130 picomole per liter (pmol/L) | Geometric Coefficient of Variation 35 |
Secondary
Time of Maximum Glucose Infusion Rate (tRmax)
Time frame: Periods 1 and 2: Baseline up to 24 hours
Population: All randomized participants who received at least 1 dose of study drug, completed at least 1 clamp procedure, and had evaluable glucodynamic data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LY2963016 | Time of Maximum Glucose Infusion Rate (tRmax) | 10.5 hour (h) |
| Lantus | Time of Maximum Glucose Infusion Rate (tRmax) | 10.2 hour (h) |
Secondary
Total Glucose Infused (Gtot)
Time frame: Periods 1 and 2: Baseline up to 24 hours
Population: All randomized participants who received at least 1 dose of study drug, completed at least 1 clamp procedure, and had evaluable glucodynamic data were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2963016 | Total Glucose Infused (Gtot) | 141 gram (g) | Geometric Coefficient of Variation 54 |
| Lantus | Total Glucose Infused (Gtot) | 160 gram (g) | Geometric Coefficient of Variation 36 |