Healthy Volunteers
Conditions
Brief summary
This study evaluated four test formulations of a glucose lowering drug (LY900014) administered by injection under the skin of the abdomen. The study was conducted in healthy people to investigate how the human body handles LY900014 and the effect of LY900014 on blood sugar levels. Side effects and tolerability were documented. The study was to be conducted in two parts (Part A and Part B) to achieve its objectives. Each part of the study was to last for about 11 to 12 weeks, including screening and follow up. Screening was required within 28 days prior to entering into either study Part A or Part B. Part B was not executed because no suitable formulation was identified.
Interventions
BIOLOGICALLY900014
Administered SC
BIOLOGICALInsulin Lispro
Administered SC
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
* Overtly healthy male or a female (not pregnant and agreeable to take birth control measures until one month after study completion) * Have a body mass index (BMI) of 18.5 to 30 kilogram per square meter (kg/m\^2), inclusive, at screening * Have normal blood pressure, pulse rate, electrocardiogram (ECG), blood and urine laboratory test results that are acceptable for the study * Are nonsmokers, have not smoked for at least 2 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
Exclusion criteria
* Are currently participating in or completed a clinical trial within the last 30 days from a clinical trial or any other type of medical research judged to be incompatible with this study * Have previously participated or withdrawn from this study * Have or used to have health problems or laboratory test results or ECG readings that, in the opinion of the doctor, could make it unsafe to participate, or could interfere with understanding the results of the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A: Pharmacokinetics (PK ): Area Under the Concentration Curve From Zero to the Last Recorded Time Post Dose (AUC0-tlast) | 30 minutes predose, 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, and 300 minutes postdose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Visual Analog Scale (VAS) Score for Injection Site Pain | Predose, 1, 20, 60 minutes postdose and at the end of the clamp procedure | The Visual Analog Scale (VAS) assessed injection site pain on a scale of 0-100 millimeter (mm) range (0 = no pain and 100 worst imaginable pain). |
| Part A: Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp | Every 10 minutes for 30 minutes predose, every 2.5 minutes for 30 minutes, then every 5 minutes for 120 minutes, then every 10 minutes for 300 minutes postdose | 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. |
| Part B: Total Amount of Glucose Infused (Gtot) Over the Duration of the Clamp - Interparticipant Variability | Every 10 minutes for 30 minutes predose, every 2.5 minutes for 30 minutes, then every 5 minutes for 120 minutes, then every 10 minutes for 300 minutes, then every 20 minutes from 300 to 480 minutes postdose | 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. |
| Part B: Pharmacokinetics (PK): Area Under the Concentration Curve From Zero to the Last Recorded Time Post Dose (AUC0-tlast) - Interparticipant Variability | Predose, 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, and 300 minutes postdose | — |
Countries
Singapore
Participant flow
Recruitment details
Part B was not executed and no data were collected.
Pre-assignment details
Part A was a 5-period crossover study of four LY900014 formulations (Tests A, B, C, and D) and insulin lispro (Reference (R)). A minimum of 3 days washout between each period.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Participants were administered LY900014 SC Tests A, B, C, and D, with that of 15 U of insulin lispro alone (Reference) in healthy subjects. | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Period 1 | Difficulty with venous cannulation | 0 | 1 | 0 | 0 | 0 |
| Period 1 | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 38.5 years STANDARD_DEVIATION 10.8 |
| Body Mass Index (BMI) | 24.43 kilogram per meter squared (kg/m²) STANDARD_DEVIATION 2.21 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 27 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 | 1 Participants |
| Region of Enrollment Singapore | 28 Participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 1 Participants |
| Weight | 72.60 kilograms (kg) STANDARD_DEVIATION 9.07 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 27 | 5 / 27 | 2 / 28 | 6 / 27 | 2 / 27 |
| serious Total, serious adverse events | 0 / 27 | 0 / 27 | 0 / 28 | 0 / 27 | 0 / 27 |
Outcome results
Primary
Part A: Pharmacokinetics (PK ): Area Under the Concentration Curve From Zero to the Last Recorded Time Post Dose (AUC0-tlast)
Time frame: 30 minutes predose, 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, and 300 minutes postdose
Population: All participants who received at least 1 dose of study drug and completed the dose sequence.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Formulation A, LY900014 | Part A: Pharmacokinetics (PK ): Area Under the Concentration Curve From Zero to the Last Recorded Time Post Dose (AUC0-tlast) | 1720 picomol times hour per liter (pmol*h/L) | Geometric Coefficient of Variation 20 |
| Part A: Formulation B, LY900014 | Part A: Pharmacokinetics (PK ): Area Under the Concentration Curve From Zero to the Last Recorded Time Post Dose (AUC0-tlast) | 1740 picomol times hour per liter (pmol*h/L) | Geometric Coefficient of Variation 17 |
| Part A: Formulation C, LY900014 | Part A: Pharmacokinetics (PK ): Area Under the Concentration Curve From Zero to the Last Recorded Time Post Dose (AUC0-tlast) | 1810 picomol times hour per liter (pmol*h/L) | Geometric Coefficient of Variation 21 |
| Part A: Formulation D, LY900014 | Part A: Pharmacokinetics (PK ): Area Under the Concentration Curve From Zero to the Last Recorded Time Post Dose (AUC0-tlast) | 1750 picomol times hour per liter (pmol*h/L) | Geometric Coefficient of Variation 19 |
| Part A: Reference | Part A: Pharmacokinetics (PK ): Area Under the Concentration Curve From Zero to the Last Recorded Time Post Dose (AUC0-tlast) | 1690 picomol times hour per liter (pmol*h/L) | Geometric Coefficient of Variation 19 |
Secondary
Part A: Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp
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.
Time frame: Every 10 minutes for 30 minutes predose, every 2.5 minutes for 30 minutes, then every 5 minutes for 120 minutes, then every 10 minutes for 300 minutes postdose
Population: All participants who received at least 1 dose of study drug and completed the dose sequence.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Formulation A, LY900014 | Part A: Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp | 78372 milligram (mg) | Geometric Coefficient of Variation 29 |
| Part A: Formulation B, LY900014 | Part A: Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp | 81776 milligram (mg) | Geometric Coefficient of Variation 41 |
| Part A: Formulation C, LY900014 | Part A: Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp | 82365 milligram (mg) | Geometric Coefficient of Variation 35 |
| Part A: Formulation D, LY900014 | Part A: Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp | 80186 milligram (mg) | Geometric Coefficient of Variation 34 |
| Part A: Reference | Part A: Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp | 75571 milligram (mg) | Geometric Coefficient of Variation 37 |
Secondary
Part A: Visual Analog Scale (VAS) Score for Injection Site Pain
The Visual Analog Scale (VAS) assessed injection site pain on a scale of 0-100 millimeter (mm) range (0 = no pain and 100 worst imaginable pain).
Time frame: Predose, 1, 20, 60 minutes postdose and at the end of the clamp procedure
Population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Formulation A, LY900014 | Part A: Visual Analog Scale (VAS) Score for Injection Site Pain | 1 minute | 0.1 millimeter (mm) | Standard Deviation 0.6 |
| Part A: Formulation A, LY900014 | Part A: Visual Analog Scale (VAS) Score for Injection Site Pain | 20 minutes | 0 millimeter (mm) | Standard Deviation 0 |
| Part A: Formulation A, LY900014 | Part A: Visual Analog Scale (VAS) Score for Injection Site Pain | 60 minutes | 0 millimeter (mm) | Standard Deviation 0 |
| Part A: Formulation A, LY900014 | Part A: Visual Analog Scale (VAS) Score for Injection Site Pain | End of clamp | 0 millimeter (mm) | Standard Deviation 0 |
| Part A: Formulation B, LY900014 | Part A: Visual Analog Scale (VAS) Score for Injection Site Pain | 1 minute | 2.1 millimeter (mm) | Standard Deviation 6.5 |
| Part A: Formulation B, LY900014 | Part A: Visual Analog Scale (VAS) Score for Injection Site Pain | End of clamp | 0 millimeter (mm) | Standard Deviation 0 |
| Part A: Formulation B, LY900014 | Part A: Visual Analog Scale (VAS) Score for Injection Site Pain | 20 minutes | 0 millimeter (mm) | Standard Deviation 0 |
| Part A: Formulation B, LY900014 | Part A: Visual Analog Scale (VAS) Score for Injection Site Pain | 60 minutes | 0 millimeter (mm) | Standard Deviation 0 |
| Part A: Formulation C, LY900014 | Part A: Visual Analog Scale (VAS) Score for Injection Site Pain | End of clamp | 0 millimeter (mm) | Standard Deviation 0 |
| Part A: Formulation C, LY900014 | Part A: Visual Analog Scale (VAS) Score for Injection Site Pain | 20 minutes | 0 millimeter (mm) | Standard Deviation 0 |
| Part A: Formulation C, LY900014 | Part A: Visual Analog Scale (VAS) Score for Injection Site Pain | 60 minutes | 0 millimeter (mm) | Standard Deviation 0 |
| Part A: Formulation C, LY900014 | Part A: Visual Analog Scale (VAS) Score for Injection Site Pain | 1 minute | 1.8 millimeter (mm) | Standard Deviation 4.8 |
| Part A: Formulation D, LY900014 | Part A: Visual Analog Scale (VAS) Score for Injection Site Pain | 1 minute | 1.3 millimeter (mm) | Standard Deviation 4.7 |
| Part A: Formulation D, LY900014 | Part A: Visual Analog Scale (VAS) Score for Injection Site Pain | 20 minutes | 2.0 millimeter (mm) | Standard Deviation 9.6 |
| Part A: Formulation D, LY900014 | Part A: Visual Analog Scale (VAS) Score for Injection Site Pain | End of clamp | 0 millimeter (mm) | Standard Deviation 0.2 |
| Part A: Formulation D, LY900014 | Part A: Visual Analog Scale (VAS) Score for Injection Site Pain | 60 minutes | 1.1 millimeter (mm) | Standard Deviation 6 |
| Part A: Reference | Part A: Visual Analog Scale (VAS) Score for Injection Site Pain | End of clamp | 0 millimeter (mm) | Standard Deviation 0 |
| Part A: Reference | Part A: Visual Analog Scale (VAS) Score for Injection Site Pain | 60 minutes | 0 millimeter (mm) | Standard Deviation 0 |
| Part A: Reference | Part A: Visual Analog Scale (VAS) Score for Injection Site Pain | 20 minutes | 0 millimeter (mm) | Standard Deviation 0 |
| Part A: Reference | Part A: Visual Analog Scale (VAS) Score for Injection Site Pain | 1 minute | 0.5 millimeter (mm) | Standard Deviation 1.9 |
Secondary
Part B: Pharmacokinetics (PK): Area Under the Concentration Curve From Zero to the Last Recorded Time Post Dose (AUC0-tlast) - Interparticipant Variability
Time frame: Predose, 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, and 300 minutes postdose
Population: Zero participants were analyzed as Part B was not executed.
Secondary
Part B: Total Amount of Glucose Infused (Gtot) Over the Duration of the Clamp - Interparticipant Variability
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.
Time frame: Every 10 minutes for 30 minutes predose, every 2.5 minutes for 30 minutes, then every 5 minutes for 120 minutes, then every 10 minutes for 300 minutes, then every 20 minutes from 300 to 480 minutes postdose
Population: Zero participants were analyzed as Part B was not executed.