Diabetes Mellitus, Type 2
Conditions
Brief summary
The study will be conducted in participants with type 2 diabetes on insulin injection therapy to investigate how the body processes LY900014 and the effect of LY900014 on blood sugar levels. Side effects and tolerability will be documented. The study will be conducted in two parts (Part A and Part B) to achieve its objectives. Participants are expected to enroll in both parts.
Interventions
DRUGLY900014
Administered subcutaneously (SC)
DRUGInsulin 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
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Are male or female participants with Type 2 Diabetes Mellitus (T2DM) on a stable multiple daily injection regimen with a short-acting as well as a long-acting insulin * Have a body mass index (BMI) ranging from 18.5 to 33.0 kilogram per square meter (kg/m²), inclusive, at screening * Have blood pressure, pulse rate, electrocardiogram (ECG), blood and urine laboratory test results acceptable for the study * Have had no episodes of severe hypoglycemia in the past 6 months (requiring assistance in treatment by a second party) * Have venous access sufficient to allow for blood sampling * Have provided written consent and are willing to follow study procedures and commit to the study duration
Exclusion criteria
* Are currently enrolled, or have participated within the last 30 days, in a clinical trial or any other type of medical research judged to be incompatible with this study * Have previously completed or withdrawn from this study * Have or used to have health problems that, in the opinion of the doctor, could make it unsafe to participate in the study * Had blood loss of more than 500 milliliters (mL) within the last month * Are treated with a continuous subcutaneous insulin infusion (insulin pump)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) (Part A) | Day 1: 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150,180, 240, 300 minutes post dose for each treatment | PK: Insulin Lispro AUC(0-5h) (Part A) |
| Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) (Part B) | Days 1 and 14: 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150,180, 240, 300 minutes post dose for each treatment | PK: Insulin Lispro AUC(0-5h) (Part B) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamics (PD): Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) of Glucose Relative to a Mixed Meal Tolerance Test (MMTT) (Part A) | Day 1: -30, -15, 0, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 135, 150, 165, 180, 195, 210, 225, 240, 300 minutes | PD: AUC(0-5h) of Glucose Relative to a MMTT (Part A) |
| Pharmacodynamics (PD): Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) of Glucose Relative to a Mixed Meal Tolerance Test (MMTT) (Part B) | Days 1 and 14: Day 1: -30, -15, 0, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 135, 150, 165, 180, 195, 210, 225, 240, 300 minutes in each study period | PD: AUC(0-5h) of Glucose Relative to a MMTT (Part B) |
Countries
Germany
Participant flow
Pre-assignment details
Two-part study compared individualized doses of LY900014 (Test) to insulin lispro (Reference). Part A: LY900014 or insulin lispro once subcutaneously (SC) before, at, or after start of meal in each of 6 periods. Minimum 1 day washout. Part B: LY900014 or insulin lispro SC before meals for 14 days. Participants were expected to complete both parts.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Individualized doses of LY900014 (Test) or insulin lispro (Reference) administered once SC at various mealtime intervals in each of six periods (Part A) and immediately before meals for 14 days (Part B). | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Period One (Part A) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 58.9 years STANDARD_DEVIATION 7.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 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 | 30 Participants |
| Region of Enrollment Germany | 30 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 29 | 0 / 30 | 1 / 29 | 2 / 29 | 3 / 29 | 0 / 29 | 6 / 30 | 0 / 14 | 1 / 15 | 0 / 27 |
| serious Total, serious adverse events | 0 / 29 | 0 / 30 | 0 / 29 | 0 / 29 | 0 / 29 | 0 / 29 | 0 / 30 | 1 / 14 | 0 / 15 | 0 / 27 |
Outcome results
Primary
Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) (Part A)
PK: Insulin Lispro AUC(0-5h) (Part A)
Time frame: Day 1: 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150,180, 240, 300 minutes post dose for each treatment
Population: All participants in Part A who received study drug and had evaluable PK data. For one participant in the LY900014 - Test (Part A) group, the insulin lispro PK profile (period two) was excluded from the mean PK analysis, as there was no absorption phase observed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro - Reference (Part A) | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) (Part A) | 1520 picomole*hour per liter (pmol*h/L) | Geometric Coefficient of Variation 62 |
| LY900014 - Test (Part A) | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) (Part A) | 1830 picomole*hour per liter (pmol*h/L) | Geometric Coefficient of Variation 68 |
Primary
Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) (Part B)
PK: Insulin Lispro AUC(0-5h) (Part B)
Time frame: Days 1 and 14: 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150,180, 240, 300 minutes post dose for each treatment
Population: All participants in Part B who received study drug and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Lispro - Reference (Part A) | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) (Part B) | Day 1 | 1390 pmol*h/L | Geometric Coefficient of Variation 86 |
| Insulin Lispro - Reference (Part A) | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) (Part B) | Day 14 | 1450 pmol*h/L | Geometric Coefficient of Variation 76 |
| LY900014 - Test (Part A) | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) (Part B) | Day 1 | 1900 pmol*h/L | Geometric Coefficient of Variation 59 |
| LY900014 - Test (Part A) | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) (Part B) | Day 14 | 1930 pmol*h/L | Geometric Coefficient of Variation 69 |
Secondary
Pharmacodynamics (PD): Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) of Glucose Relative to a Mixed Meal Tolerance Test (MMTT) (Part A)
PD: AUC(0-5h) of Glucose Relative to a MMTT (Part A)
Time frame: Day 1: -30, -15, 0, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 135, 150, 165, 180, 195, 210, 225, 240, 300 minutes
Population: All participants in Part A who received study drug immediately before a meal (0 min) and had evaluable PD data. Data were excluded if the participant did not keep identical insulin lispro dose during the MMTT assessments, did not complete the entire test meal, or had significant changes in nutrient consumption of the test meal.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro - Reference (Part A) | Pharmacodynamics (PD): Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) of Glucose Relative to a Mixed Meal Tolerance Test (MMTT) (Part A) | 524 milligram*hour/deciliter (mg*h/dL) | Standard Deviation 146 |
| LY900014 - Test (Part A) | Pharmacodynamics (PD): Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) of Glucose Relative to a Mixed Meal Tolerance Test (MMTT) (Part A) | 395 milligram*hour/deciliter (mg*h/dL) | Standard Deviation 124 |
Secondary
Pharmacodynamics (PD): Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) of Glucose Relative to a Mixed Meal Tolerance Test (MMTT) (Part B)
PD: AUC(0-5h) of Glucose Relative to a MMTT (Part B)
Time frame: Days 1 and 14: Day 1: -30, -15, 0, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 135, 150, 165, 180, 195, 210, 225, 240, 300 minutes in each study period
Population: All participants in Part B who received study drug and had evaluable PD data. Data were excluded if the participant did not keep identical insulin lispro dose during the MMTT assessments, did not complete the entire test meal, or had significant changes in nutrient consumption of the test meal.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Lispro - Reference (Part A) | Pharmacodynamics (PD): Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) of Glucose Relative to a Mixed Meal Tolerance Test (MMTT) (Part B) | Day 1 | 439 mg*h/dL | Standard Deviation 104 |
| Insulin Lispro - Reference (Part A) | Pharmacodynamics (PD): Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) of Glucose Relative to a Mixed Meal Tolerance Test (MMTT) (Part B) | Day 14 | 453 mg*h/dL | Standard Deviation 133 |
| LY900014 - Test (Part A) | Pharmacodynamics (PD): Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) of Glucose Relative to a Mixed Meal Tolerance Test (MMTT) (Part B) | Day 1 | 407 mg*h/dL | Standard Deviation 163 |
| LY900014 - Test (Part A) | Pharmacodynamics (PD): Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) of Glucose Relative to a Mixed Meal Tolerance Test (MMTT) (Part B) | Day 14 | 387 mg*h/dL | Standard Deviation 151 |