Diabetes Mellitus, Type 1
Conditions
Brief summary
The purpose of this study is to compare LY900014 with insulin lispro (Humalog) in elderly and younger adults with type 1 diabetes mellitus. Screening is required within 28 days prior to the start of the study. For each participant, the total duration of the clinical trial will be between 3 to 8 weeks.
Interventions
DRUGLY900014
Administered 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 No maximum
Healthy volunteers
No
Inclusion criteria
* Are male or female participants with Type 1 Diabetes Mellitus (T1DM) * Have a body mass index (BMI) of 18.5 to 30.0 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 * Have a history of renal impairment * Have a history of deep vein thrombosis of the leg or repeated episodes of deep leg vein thrombosis in first-degree relatives * Have proliferative retinopathy or maculopathy and/or severe neuropathy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) for Each Treatment Arm | Day 1: Pre-dose, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, 300, 360, 420, 480, 540, and 600 minutes post-dose | Pharmacokinetics: Insulin lispro AUC from time zero to 10 hours postdose \[AUC(0-10h)\] for each treatment arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Amount of Glucose Infused (Gtot) Over Duration of Clamp for Each Treatment Arm | Every minute starting from the pre-dose and throughout the duration of the clamp until 10 hours post-dose | Glucodynamics: Gtot is the total glucose infusion over the clamp duration (10 hours) and is used to measure the study drug action over time as measured by the euglycemic clamp procedure. |
Countries
Germany
Participant flow
Pre-assignment details
This is a 2-period, crossover study, up to 10-hour euglycemic clamp in which participants were randomized to 1 of 2 treatment sequences: LY900014 in Period 1 switching to Humalog period 2 or Humalog in Period 1 switching to LY900014 in Period 2. A washout period of 3 to 15 days occurred between study drug administration.
Participants by arm
| Arm | Count |
|---|---|
| Elderly Adults Male and female participants age 65 or older inclusive. | 39 |
| Younger Adults Male and female participants age 18 to 45 inclusive. | 41 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Treatment Period 1 | Adverse Event | 0 | 0 | 1 | 0 |
| Wash-out Period | Adverse Event | 0 | 1 | 1 | 0 |
| Wash-out Period | Withdrawal by Subject | 0 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Elderly Adults | Total | Younger Adults |
|---|---|---|---|
| Age, Continuous | 68.5 years STANDARD_DEVIATION 2.7 | 49.8 years STANDARD_DEVIATION 19.1 | 32.0 years STANDARD_DEVIATION 6.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 80 Participants | 41 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 | 39 Participants | 80 Participants | 41 Participants |
| Region of Enrollment Germany | 39 Participants | 80 Participants | 41 Participants |
| Sex: Female, Male Female | 17 Participants | 30 Participants | 13 Participants |
| Sex: Female, Male Male | 22 Participants | 50 Participants | 28 Participants |
| Weight | 76.66 kilograms (kg) STANDARD_DEVIATION 12.61 | 77.55 kilograms (kg) STANDARD_DEVIATION 11.41 | 78.39 kilograms (kg) STANDARD_DEVIATION 10 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 37 | 0 / 38 | 0 / 40 | 0 / 39 |
| other Total, other adverse events | 5 / 37 | 7 / 38 | 3 / 40 | 6 / 39 |
| serious Total, serious adverse events | 0 / 37 | 0 / 38 | 1 / 40 | 0 / 39 |
Outcome results
Primary
Pharmacokinetics: Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) for Each Treatment Arm
Pharmacokinetics: Insulin lispro AUC from time zero to 10 hours postdose \[AUC(0-10h)\] for each treatment arm.
Time frame: Day 1: Pre-dose, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, 300, 360, 420, 480, 540, and 600 minutes post-dose
Population: All participants who received at least one dose of study drug and have measurable insulin lispro concentrations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Elderly Adults LY900014 | Pharmacokinetics: Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) for Each Treatment Arm | 1430 picomole * hour per Liter (pmol*h/L) | Geometric Coefficient of Variation 26 |
| Elderly Adults Humalog | Pharmacokinetics: Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) for Each Treatment Arm | 1400 picomole * hour per Liter (pmol*h/L) | Geometric Coefficient of Variation 29 |
| Younger Adults LY900014 | Pharmacokinetics: Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) for Each Treatment Arm | 1210 picomole * hour per Liter (pmol*h/L) | Geometric Coefficient of Variation 24 |
| Younger Adults Humalog | Pharmacokinetics: Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) for Each Treatment Arm | 1170 picomole * hour per Liter (pmol*h/L) | Geometric Coefficient of Variation 30 |
Comparison: Geometric LSMeans were controlled for injection site, study period, and sequence as fixed effects, and subject within sequence as a random effect.95% CI: [0.953, 1.1]Mixed Models Analysis
Comparison: Geometric Least Squares Means (LSMeans) were controlled for injection site, study period, and sequence as fixed effects, and subject within sequence as a random effect.95% CI: [0.974, 1.09]Mixed Models Analysis
Secondary
Total Amount of Glucose Infused (Gtot) Over Duration of Clamp for Each Treatment Arm
Glucodynamics: Gtot is the total glucose infusion over the clamp duration (10 hours) and is used to measure the study drug action over time as measured by the euglycemic clamp procedure.
Time frame: Every minute starting from the pre-dose and throughout the duration of the clamp until 10 hours post-dose
Population: All participants who received at least one dose of study drug and completed at least one clamp procedure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Elderly Adults LY900014 | Total Amount of Glucose Infused (Gtot) Over Duration of Clamp for Each Treatment Arm | 1140 milligram per kilogram (mg/kg) | Geometric Coefficient of Variation 42 |
| Elderly Adults Humalog | Total Amount of Glucose Infused (Gtot) Over Duration of Clamp for Each Treatment Arm | 1090 milligram per kilogram (mg/kg) | Geometric Coefficient of Variation 43 |
| Younger Adults LY900014 | Total Amount of Glucose Infused (Gtot) Over Duration of Clamp for Each Treatment Arm | 1170 milligram per kilogram (mg/kg) | Geometric Coefficient of Variation 33 |
| Younger Adults Humalog | Total Amount of Glucose Infused (Gtot) Over Duration of Clamp for Each Treatment Arm | 1150 milligram per kilogram (mg/kg) | Geometric Coefficient of Variation 30 |
Comparison: Geometric LSMeans were controlled for injection site, study period, and sequence as fixed effects, and subject within sequence as a random effect.95% CI: [0.96, 1.12]Mixed Models Analysis
Comparison: Geometric LSMeans were controlled for injection site, study period, and sequence as fixed effects, and subject within sequence as a random effect.95% CI: [0.94, 1.1]Mixed Models Analysis