Diabetes Mellitus, Type 1
Conditions
Brief summary
The main purpose of this study is to compare LY900014 to insulin lispro (Humalog) in participants with type 1 diabetes who are using an insulin pump and have high blood sugar after eating. For each participant, the study will last about two to nine weeks.
Interventions
DRUGLY900014
Administered by CSII
DRUGInsulin Lispro
Administered by CSII
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 64 Years
Healthy volunteers
No
Inclusion criteria
* Male or female participants with type 1 diabetes * Body mass index (BMI) between 18.5 and 30.0 kilograms per square meter, inclusive * Hemoglobin A1c (HbA1c) less than or equal to 8.5 percent (%) * Using CSII and stable insulin regimen for at least 3 months prior to inclusion into the trial
Exclusion criteria
* Known or suspected hypersensitivity to investigational medical product(s) or related products * Receipt of any medicinal product in clinical development within 30 days or at least 5 half-lives of the related substances and their metabolites (whichever is longer) before randomization in this trial * Known slowing of gastric emptying and or gastrointestinal surgery that, in the opinion of the investigator, might change gastrointestinal motility and food absorption * Proliferative retinopathy or maculopathy as judged by the Investigator based on a recent (less than 1.5 years) ophthalmologic examination * Widespread subcutaneous lipodystrophy in the abdomen * Current use of any glucose-lowering agents other than insulin within 3 months prior to screening * Chronic or recent use of corticosteroids
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Recovery From Hyperglycemia Following Administration of LY900014 and Insulin Lispro (Humalog) After Missed Meal Bolus | Day 1: Baseline up to 5 hours after missed meal bolus | Time to Recovery from Hyperglycemia was defined as tPG140 = time to achieve glucose of 140 Milligrams per deciliter (mg/dL). |
| Time to Recovery From Hyperglycemia Following Administration of LY900014 and Insulin Lispro (Humalog) After Pump Suspension | Day 2: Baseline up to 5 hours after pump suspension | Time to Recovery from Hyperglycemia was defined as tPG140 = time to achieve glucose of 140 mg/dL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamics (PD): Maximum Observed Plasma Glucose (PGmax) Following Administration of LY900014 and Insulin Lispro (Humalog) | Day 1: Baseline up to 5 hours after missed meal bolus and Day 2: Baseline up to 5 hours after pump suspension | PD: PGmax following administration of LY900014 and insulin lispro (Humalog) |
| Pharmacokinetics (PK): Time to Maximum Observed Insulin Lispro Concentration (Tmax) Following Administration of LY900014 and Insulin Lispro (Humalog) | Day 1: Baseline up to 5 hours after missed meal bolus and Day 2: Baseline up to 5 hours after pump suspension | PK: Tmax following administration of LY900014 and insulin lispro (Humalog) |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 100 U/mL LY900014 and 100 U/mL Insulin Lispro (Humalog) Participants received 100 U/mL LY900014 administered by CSII in one of two study periods.
Participants received 100 U/mL Insulin Lispro (Humalog) administered by CSII in one of two study periods. | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | 100 U/mL LY900014 and 100 U/mL Insulin Lispro (Humalog) |
|---|---|
| Age, Continuous | 33.8 years STANDARD_DEVIATION 9.57 |
| 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 | 32 Participants |
| Region of Enrollment Germany | 32 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 32 |
| other Total, other adverse events | 3 / 31 | 2 / 32 |
| serious Total, serious adverse events | 0 / 31 | 0 / 32 |
Outcome results
Primary
Time to Recovery From Hyperglycemia Following Administration of LY900014 and Insulin Lispro (Humalog) After Missed Meal Bolus
Time to Recovery from Hyperglycemia was defined as tPG140 = time to achieve glucose of 140 Milligrams per deciliter (mg/dL).
Time frame: Day 1: Baseline up to 5 hours after missed meal bolus
Population: All participants who received both study treatments with the same insulin dose and achieved recovery from hyperglycemia on day 1
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 100 U/mL LY900014 | Time to Recovery From Hyperglycemia Following Administration of LY900014 and Insulin Lispro (Humalog) After Missed Meal Bolus | 1.79 Hours |
| 100 U/mL Insulin Lispro (Humalog) | Time to Recovery From Hyperglycemia Following Administration of LY900014 and Insulin Lispro (Humalog) After Missed Meal Bolus | 2.55 Hours |
p-value: 0.14595% CI: [-0.896, 0.142]Mixed Models Analysis
Primary
Time to Recovery From Hyperglycemia Following Administration of LY900014 and Insulin Lispro (Humalog) After Pump Suspension
Time to Recovery from Hyperglycemia was defined as tPG140 = time to achieve glucose of 140 mg/dL.
Time frame: Day 2: Baseline up to 5 hours after pump suspension
Population: All participants who received both study treatments with the same insulin dose and achieved recovery from hyperglycemia on day 2
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 100 U/mL LY900014 | Time to Recovery From Hyperglycemia Following Administration of LY900014 and Insulin Lispro (Humalog) After Pump Suspension | 1.53 Hours |
| 100 U/mL Insulin Lispro (Humalog) | Time to Recovery From Hyperglycemia Following Administration of LY900014 and Insulin Lispro (Humalog) After Pump Suspension | 1.78 Hours |
p-value: 0.00195% CI: [-0.406, -0.117]Mixed Models Analysis
Secondary
Pharmacodynamics (PD): Maximum Observed Plasma Glucose (PGmax) Following Administration of LY900014 and Insulin Lispro (Humalog)
PD: PGmax following administration of LY900014 and insulin lispro (Humalog)
Time frame: Day 1: Baseline up to 5 hours after missed meal bolus and Day 2: Baseline up to 5 hours after pump suspension
Population: All participants who received both study treatments with the same insulin dose and achieved recovery from hyperglycemia on days 1 and 2
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 100 U/mL LY900014 | Pharmacodynamics (PD): Maximum Observed Plasma Glucose (PGmax) Following Administration of LY900014 and Insulin Lispro (Humalog) | Day 1 | 297 Milligrams per deciliter (mg/dL) | Standard Deviation 27.6 |
| 100 U/mL LY900014 | Pharmacodynamics (PD): Maximum Observed Plasma Glucose (PGmax) Following Administration of LY900014 and Insulin Lispro (Humalog) | Day 2 | 259 Milligrams per deciliter (mg/dL) | Standard Deviation 11.1 |
| 100 U/mL Insulin Lispro (Humalog) | Pharmacodynamics (PD): Maximum Observed Plasma Glucose (PGmax) Following Administration of LY900014 and Insulin Lispro (Humalog) | Day 1 | 309 Milligrams per deciliter (mg/dL) | Standard Deviation 24.9 |
| 100 U/mL Insulin Lispro (Humalog) | Pharmacodynamics (PD): Maximum Observed Plasma Glucose (PGmax) Following Administration of LY900014 and Insulin Lispro (Humalog) | Day 2 | 265 Milligrams per deciliter (mg/dL) | Standard Deviation 9.26 |
Comparison: Day 1p-value: 0.017395% CI: [-22.73, -2.49]Mixed Models Analysis
Comparison: Day 2p-value: 0.024395% CI: [-10.69, 0.81]Mixed Models Analysis
Secondary
Pharmacokinetics (PK): Time to Maximum Observed Insulin Lispro Concentration (Tmax) Following Administration of LY900014 and Insulin Lispro (Humalog)
PK: Tmax following administration of LY900014 and insulin lispro (Humalog)
Time frame: Day 1: Baseline up to 5 hours after missed meal bolus and Day 2: Baseline up to 5 hours after pump suspension
Population: All participants who received both study treatments with the same insulin dose and achieved recovery from hyperglycemia on days 1 and 2
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 100 U/mL LY900014 | Pharmacokinetics (PK): Time to Maximum Observed Insulin Lispro Concentration (Tmax) Following Administration of LY900014 and Insulin Lispro (Humalog) | Day 1 | 0.75 Hours |
| 100 U/mL LY900014 | Pharmacokinetics (PK): Time to Maximum Observed Insulin Lispro Concentration (Tmax) Following Administration of LY900014 and Insulin Lispro (Humalog) | Day 2 | 0.92 Hours |
| 100 U/mL Insulin Lispro (Humalog) | Pharmacokinetics (PK): Time to Maximum Observed Insulin Lispro Concentration (Tmax) Following Administration of LY900014 and Insulin Lispro (Humalog) | Day 1 | 0.83 Hours |
| 100 U/mL Insulin Lispro (Humalog) | Pharmacokinetics (PK): Time to Maximum Observed Insulin Lispro Concentration (Tmax) Following Administration of LY900014 and Insulin Lispro (Humalog) | Day 2 | 0.92 Hours |
Comparison: Day 1p-value: 0.945Mixed Models Analysis
Comparison: Day 2p-value: 0.888Mixed Models Analysis