Diabetes Mellitus, Type 1
Conditions
Brief summary
This study will be conducted in participants with type 1 diabetes mellitus to investigate how the human body processes LY900014, a new blood sugar lowering insulin, and its effect on blood sugar levels when it is delivered via an insulin pump. Side effects and tolerability will be documented. The study will last about 4 to 11 weeks for each participant.
Interventions
DRUGLY900014
Administered subcutaneously (SC)
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
* Male or female participants with Type 1 Diabetes Mellitus (T1DM) who are receiving insulin therapy via an approved insulin pump * Have a screening body mass index (BMI) of greater than 18.5 to 33.0 kilograms per meter squared (kg/m²), inclusive * Have medical and laboratory test results that are acceptable for the study * Have had no episodes of severe hypoglycemia (requiring assistance in treatment by a second party) in the past 6 months * 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 participating or recently participated in a clinical trial or any other type of medical research judged to be incompatible with this study * Had blood loss of more than 500 milliliters (mL) within the last month * Have known allergies to LY900014, insulin lispro, related compounds or any components in the study drug formulations * Have previously participated or withdrawn from this study * Have or used to have health problems or medical test results that, in the opinion of the doctor, could make it unsafe to participate, or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 | Description |
|---|---|---|
| Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC [0-5 h]) of Following Administration of Each Study Arm With a Standard Dual-wave Bolus | Days 1 and 3: -15, 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, and 300 minutes post dose | PK: Insulin Lispro AUC(0-5h) |
| Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours(h) (AUC [0-5 h]) Following Administration of Each Study Arm With a Standard Single-wave Bolus | Days 1 and 3: -15, 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, and 300 minutes post dose | PK: Insulin Lispro AUC(0-5h) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glucodynamics (GD): Change From Baseline Area Under the Concentration Curve From Time Zero to 5 Hours (AUC [0-5h]) of Glucose Relative to Mixed Meal Tolerance Test Following Administration of Each Study Arm With a Standard Single-wave Bolus | Days 1 and 3: -30, -15, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 135, 150, 165, 180,195, 210, 225, 240, and 300 minutes post dose | GD: Change from baseline in AUC (0-5h) of glucose relative to mixed meal tolerance test (MMTT). |
| Glucodynamics (GD): Change From Baseline Area Under the Concentration Curve From Time Zero to 5 Hours (AUC [0-5 h]) of Glucose Relative to MMTT Following Administration of Each Study Arm With a Standard Dual-wave Bolus | Day 1 and 3: -30, -15, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 135, 150, 165, 180,195, 210, 225, 240, and 300 minutes post dose | GD: Change from baseline in AUC (0-5h) of glucose relative to MMTT. |
Countries
Germany
Participant flow
Recruitment details
For the time between consecutive periods, participants continued their CSII with their personal pump using Insulin lispro (Humalog) until the evening of Day -1 (after administration of the standardized dinner) of the next period when they will receive either LY900014 or Insulin lispro (Humalog), according to assigned treatment.
Pre-assignment details
Participants were randomized to receive LY900014 and Insulin lispro (Humalog) via CSII with intermittent bolus doses, standard single-wave (SS) and standard dual-wave (SD) immediately before meals, over 3 days per period.
Participants by arm
| Arm | Count |
|---|---|
| Overall Baseline Participants received individualized doses of LY900014 and Insulin lispro (Humalog) via CSII with various intermittent bolus doses immediately before meals, over 3 days per period. | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Overall Baseline |
|---|---|
| Age, Continuous | 48.6 years STANDARD_DEVIATION 11.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 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 | 24 Participants |
| Region of Enrollment Germany | 24 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 24 | 0 / 24 |
| other Total, other adverse events | 19 / 24 | 18 / 24 | 10 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 24 |
Outcome results
Primary
Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC [0-5 h]) of Following Administration of Each Study Arm With a Standard Dual-wave Bolus
PK: Insulin Lispro AUC(0-5h)
Time frame: Days 1 and 3: -15, 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, and 300 minutes post dose
Population: All participants who received both study drugs and had evaluable PK during the breakfast test meal.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LY900014 SS | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC [0-5 h]) of Following Administration of Each Study Arm With a Standard Dual-wave Bolus | Day 1 | 985 pmol*h/L | Geometric Coefficient of Variation 48 |
| LY900014 SS | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC [0-5 h]) of Following Administration of Each Study Arm With a Standard Dual-wave Bolus | Day 3 | 1010 pmol*h/L | Geometric Coefficient of Variation 53 |
| Insulin Lispro (Humalog) SS | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC [0-5 h]) of Following Administration of Each Study Arm With a Standard Dual-wave Bolus | Day 1 | 956 pmol*h/L | Geometric Coefficient of Variation 46 |
| Insulin Lispro (Humalog) SS | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC [0-5 h]) of Following Administration of Each Study Arm With a Standard Dual-wave Bolus | Day 3 | 969 pmol*h/L | Geometric Coefficient of Variation 48 |
Comparison: Day 190% CI: [0.808, 1.31]
90% CI: [0.82, 1.32]
Primary
Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours(h) (AUC [0-5 h]) Following Administration of Each Study Arm With a Standard Single-wave Bolus
PK: Insulin Lispro AUC(0-5h)
Time frame: Days 1 and 3: -15, 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, and 300 minutes post dose
Population: All participants who received at least one dose of both study drugs and had evaluable PK data during the breakfast test meal.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LY900014 SS | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours(h) (AUC [0-5 h]) Following Administration of Each Study Arm With a Standard Single-wave Bolus | Day 1 | 1040 picomole x hour per liter (pmol*h/L) | Geometric Coefficient of Variation 42 |
| LY900014 SS | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours(h) (AUC [0-5 h]) Following Administration of Each Study Arm With a Standard Single-wave Bolus | Day 3 | 1050 picomole x hour per liter (pmol*h/L) | Geometric Coefficient of Variation 47 |
| Insulin Lispro (Humalog) SS | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours(h) (AUC [0-5 h]) Following Administration of Each Study Arm With a Standard Single-wave Bolus | Day 1 | 1040 picomole x hour per liter (pmol*h/L) | Geometric Coefficient of Variation 43 |
| Insulin Lispro (Humalog) SS | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours(h) (AUC [0-5 h]) Following Administration of Each Study Arm With a Standard Single-wave Bolus | Day 3 | 1040 picomole x hour per liter (pmol*h/L) | Geometric Coefficient of Variation 48 |
Comparison: Day 190% CI: [0.81, 1.23]
Comparison: Day 390% CI: [0.817, 1.25]
Secondary
Glucodynamics (GD): Change From Baseline Area Under the Concentration Curve From Time Zero to 5 Hours (AUC [0-5h]) of Glucose Relative to Mixed Meal Tolerance Test Following Administration of Each Study Arm With a Standard Single-wave Bolus
GD: Change from baseline in AUC (0-5h) of glucose relative to mixed meal tolerance test (MMTT).
Time frame: Days 1 and 3: -30, -15, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 135, 150, 165, 180,195, 210, 225, 240, and 300 minutes post dose
Population: All participants who received at least one dose of both study drugs and had evaluable GD during the breakfast test meal. Last observation carried forward (LOCF) was used for last observed glucose values prior to treatment intervention for hypoglycemic or hyperglycemic events.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LY900014 SS | Glucodynamics (GD): Change From Baseline Area Under the Concentration Curve From Time Zero to 5 Hours (AUC [0-5h]) of Glucose Relative to Mixed Meal Tolerance Test Following Administration of Each Study Arm With a Standard Single-wave Bolus | Day 3 | 140 milligrams * hour/deciliter (mg*h/dL) | Standard Deviation 223 |
| LY900014 SS | Glucodynamics (GD): Change From Baseline Area Under the Concentration Curve From Time Zero to 5 Hours (AUC [0-5h]) of Glucose Relative to Mixed Meal Tolerance Test Following Administration of Each Study Arm With a Standard Single-wave Bolus | Day 1 | 16.8 milligrams * hour/deciliter (mg*h/dL) | Standard Deviation 182 |
| Insulin Lispro (Humalog) SS | Glucodynamics (GD): Change From Baseline Area Under the Concentration Curve From Time Zero to 5 Hours (AUC [0-5h]) of Glucose Relative to Mixed Meal Tolerance Test Following Administration of Each Study Arm With a Standard Single-wave Bolus | Day 1 | 38.9 milligrams * hour/deciliter (mg*h/dL) | Standard Deviation 186 |
| Insulin Lispro (Humalog) SS | Glucodynamics (GD): Change From Baseline Area Under the Concentration Curve From Time Zero to 5 Hours (AUC [0-5h]) of Glucose Relative to Mixed Meal Tolerance Test Following Administration of Each Study Arm With a Standard Single-wave Bolus | Day 3 | 175 milligrams * hour/deciliter (mg*h/dL) | Standard Deviation 152 |
Secondary
Glucodynamics (GD): Change From Baseline Area Under the Concentration Curve From Time Zero to 5 Hours (AUC [0-5 h]) of Glucose Relative to MMTT Following Administration of Each Study Arm With a Standard Dual-wave Bolus
GD: Change from baseline in AUC (0-5h) of glucose relative to MMTT.
Time frame: Day 1 and 3: -30, -15, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 135, 150, 165, 180,195, 210, 225, 240, and 300 minutes post dose
Population: All participants who received at least one dose of both study drugs and had evaluable GD data during the breakfast test meal. LOCF was used for last observed glucose values prior to treatment intervention for hypoglycemic or hyperglycemic events.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LY900014 SS | Glucodynamics (GD): Change From Baseline Area Under the Concentration Curve From Time Zero to 5 Hours (AUC [0-5 h]) of Glucose Relative to MMTT Following Administration of Each Study Arm With a Standard Dual-wave Bolus | Day 1 | -1.87 mg*h/dL | Standard Deviation 225 |
| LY900014 SS | Glucodynamics (GD): Change From Baseline Area Under the Concentration Curve From Time Zero to 5 Hours (AUC [0-5 h]) of Glucose Relative to MMTT Following Administration of Each Study Arm With a Standard Dual-wave Bolus | Day 3 | 188 mg*h/dL | Standard Deviation 234 |
| Insulin Lispro (Humalog) SS | Glucodynamics (GD): Change From Baseline Area Under the Concentration Curve From Time Zero to 5 Hours (AUC [0-5 h]) of Glucose Relative to MMTT Following Administration of Each Study Arm With a Standard Dual-wave Bolus | Day 1 | 106 mg*h/dL | Standard Deviation 178 |
| Insulin Lispro (Humalog) SS | Glucodynamics (GD): Change From Baseline Area Under the Concentration Curve From Time Zero to 5 Hours (AUC [0-5 h]) of Glucose Relative to MMTT Following Administration of Each Study Arm With a Standard Dual-wave Bolus | Day 3 | 286 mg*h/dL | Standard Deviation 221 |