Diabetes Mellitus, Type 1
Conditions
Brief summary
Two forms of insulin lispro (LY900014 and Humalog®) and two forms of insulin aspart (NovoRapid® and Fiasp®) will be given to trial participants with diabetes mellitus type 1 by injection under the skin. The study will assess how fast the active ingredient (insulin lispro or insulin aspart) gets into the blood stream and how long it takes the body to remove it. A test meal will be given to trial participants to assess the course of the blood sugar lowering effect of the investigational products. The safety and tolerability of LY900014 will also be assessed. Screening is required within 14 days prior to the lead in. For each participant, the study will last up to 91 days.
Interventions
DRUGLY900014
Administered SC
DRUGInsulin Lispro
Administered SC
DRUGInsulin Aspart
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
Yes
Inclusion criteria
* Are male or female participants with Type 1 Diabetes Mellitus (T1DM) for at least 1 year * Have a body mass index (BMI) of 18.5 to 35.0 kilogram per meter square (kg/m²) * Have a glycated hemoglobin (HbA1c) less than (\<)9.0 percent (%) * Have had no episodes of severe hypoglycaemia in the last 6 months
Exclusion criteria
\- Have a history or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine (apart from T1DM), hematological, or neurological disorders capable of significantly altering the absorption, metabolism or elimination of drugs; of constituting a risk when taking the investigational product; or of interfering with the interpretation of data
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Insulin Lispro or Insulin Aspart Area Under the Concentration Curve From Zero to Seven Hours (AUC 0-7h) Following Administration of Each Study Arm | 0 (predose), 1, 2, 3,5,10, 15, 20, 25, 30,35, 40, 45, 50, 55,60, 70, 90, 120, 150,180, 240, 300, 360 and 420 minutes postdose | PK: Insulin Lispro or Insulin Aspart AUC(0-7h) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamics (PD): Change From Baseline Area Under the Concentration Curve of Glucose Relative to a Mixed Meal Tolerance Test (MMTT) | Time Frame:-30, -15, 0 (predose), 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 135, 150, 165, 180, 195, 210, 225, 240, and 300 minutes postdose | PD: AUC(0-5h) of Glucose Relative to a Mixed Meal Tolerance Test (MMTT) |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| T1DM Cohort All randomized participants with T1DM participants who received at least 1 dose of study drug. | 68 |
| Healthy Participants All healthy participants. | 12 |
| Total | 80 |
Baseline characteristics
| Characteristic | T1DM Cohort | Healthy Participants | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 0 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 61 Participants | 12 Participants | 73 Participants |
| Body Mass Index (BMI) | 25.82 kilograms per meter squared STANDARD_DEVIATION 2.36 | 25.38 kilograms per meter squared STANDARD_DEVIATION 1.8 | 25.38 kilograms per meter squared STANDARD_DEVIATION 1.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 67 Participants | 12 Participants | 79 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 68 Participants | 12 Participants | 80 Participants |
| Region of Enrollment Germany | 68 participants | 12 participants | 0 participants |
| Sex: Female, Male Female | 17 Participants | 0 Participants | 17 Participants |
| Sex: Female, Male Male | 51 Participants | 12 Participants | 63 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 68 | 0 / 67 | 0 / 68 | 0 / 67 | 0 / 12 |
| other Total, other adverse events | 0 / 68 | 0 / 67 | 0 / 68 | 0 / 67 | 0 / 12 |
| serious Total, serious adverse events | 0 / 68 | 0 / 67 | 0 / 68 | 0 / 67 | 0 / 12 |
Outcome results
Primary
Pharmacokinetics (PK): Insulin Lispro or Insulin Aspart Area Under the Concentration Curve From Zero to Seven Hours (AUC 0-7h) Following Administration of Each Study Arm
PK: Insulin Lispro or Insulin Aspart AUC(0-7h)
Time frame: 0 (predose), 1, 2, 3,5,10, 15, 20, 25, 30,35, 40, 45, 50, 55,60, 70, 90, 120, 150,180, 240, 300, 360 and 420 minutes postdose
Population: All randomized, T1DM participants who received at least 1 dose of study drug.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY900014 | Pharmacokinetics (PK): Insulin Lispro or Insulin Aspart Area Under the Concentration Curve From Zero to Seven Hours (AUC 0-7h) Following Administration of Each Study Arm | 786 picomols times hour per Liter | Geometric Coefficient of Variation 36 |
| Insulin Lispro (Humalog®) | Pharmacokinetics (PK): Insulin Lispro or Insulin Aspart Area Under the Concentration Curve From Zero to Seven Hours (AUC 0-7h) Following Administration of Each Study Arm | 756 picomols times hour per Liter | Geometric Coefficient of Variation 37 |
| Insulin Aspart (NovoRapid®) | Pharmacokinetics (PK): Insulin Lispro or Insulin Aspart Area Under the Concentration Curve From Zero to Seven Hours (AUC 0-7h) Following Administration of Each Study Arm | 938 picomols times hour per Liter | Geometric Coefficient of Variation 41 |
| Insulin Aspart (Fiasp®) | Pharmacokinetics (PK): Insulin Lispro or Insulin Aspart Area Under the Concentration Curve From Zero to Seven Hours (AUC 0-7h) Following Administration of Each Study Arm | 928 picomols times hour per Liter | Geometric Coefficient of Variation 36 |
95% CI: [0.985, 1.1]
Secondary
Pharmacodynamics (PD): Change From Baseline Area Under the Concentration Curve of Glucose Relative to a Mixed Meal Tolerance Test (MMTT)
PD: AUC(0-5h) of Glucose Relative to a Mixed Meal Tolerance Test (MMTT)
Time frame: Time Frame:-30, -15, 0 (predose), 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 135, 150, 165, 180, 195, 210, 225, 240, and 300 minutes postdose
Population: All randomized participants who evaluable PD parameters.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LY900014 | Pharmacodynamics (PD): Change From Baseline Area Under the Concentration Curve of Glucose Relative to a Mixed Meal Tolerance Test (MMTT) | 81.5 milligrams times hour per deciliter | Standard Deviation 212 |
| Insulin Lispro (Humalog®) | Pharmacodynamics (PD): Change From Baseline Area Under the Concentration Curve of Glucose Relative to a Mixed Meal Tolerance Test (MMTT) | 141 milligrams times hour per deciliter | Standard Deviation 224 |
| Insulin Aspart (NovoRapid®) | Pharmacodynamics (PD): Change From Baseline Area Under the Concentration Curve of Glucose Relative to a Mixed Meal Tolerance Test (MMTT) | 157 milligrams times hour per deciliter | Standard Deviation 243 |
| Insulin Aspart (Fiasp®) | Pharmacodynamics (PD): Change From Baseline Area Under the Concentration Curve of Glucose Relative to a Mixed Meal Tolerance Test (MMTT) | 101 milligrams times hour per deciliter | Standard Deviation 226 |
| Healthy Participants | Pharmacodynamics (PD): Change From Baseline Area Under the Concentration Curve of Glucose Relative to a Mixed Meal Tolerance Test (MMTT) | 44.1 milligrams times hour per deciliter | Standard Deviation 32.5 |