Type 1 Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to compare LY900014 with insulin lispro (Humalog) in participants with type 1 diabetes mellitus. There are 2 parts to this study. Part A is investigating how the body processes LY900014 and the effect of LY900014 on blood sugar levels compared to insulin lispro (Humalog) when study treatment is given by subcutaneous injection. Part B of the study is investigating how the body processes LY900014 and the effect of LY900014 on blood sugar levels compared to insulin lispro (Humalog) when study treatment is given by continuous subcutaneous insulin infusion (CSII) pump. Screening is required within 28 days prior to the start of the study. For each participant, the study will last about 40 days in each part.
Interventions
DRUGLY900014
Administered via SC injection
DRUGInsulin Lispro
Administered via SC injection
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
6 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Are male or female participants aged 6-64 with Type 1 Diabetes Mellitus (T1DM) for at least 1 year * Have a glycated hemoglobin (HbA1c) less than (\<)10.0 percent (%)
Exclusion criteria
* Receiving any oral or injectable medication intended for the treatment of diabetes mellitus other than insulins in the 12 months prior to screening * More than one episode of severe hypoglycaemia in the last 6 months * Presence of clinically significant hematologic, oncologic, renal, cardiac, hepatic, or gastrointestinal disease, proliferative retinopathy, uncontrolled celiac disease, uncontrolled hyperthyroidism or hypothyroidism, or adrenal insufficiency * Have obvious clinical signs or symptoms of liver disease * Have a history of renal impairment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve (AUC) Following Each Treatment Arm for Each Study Part | Predose, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 90, 120, 150, 180, 240, 300, 360, and 420 minutes postdose | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve (AUC(0 -7h)) following Each Treatment Arm for Each Study Part. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glucodynamics (GD): Area Under the Baseline Subtracted Glucose Concentration Versus Time Curve Following Each Treatment Arm for Each Study Part | -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 | Glucodynamics (GD): Area Under the Baseline Subtracted Glucose Concentration Versus Time Curve (BG∆AUC(0-5h)) Following Each Treatment Arm for Each Study Part. |
Countries
Canada, Germany
Participant flow
Recruitment details
Participants (pts) who completed Part A but discontinued before the beginning of Part B were replaced by newly enrolled participants in Part B.
Pre-assignment details
Two period crossover study, with a minimum of 22 days washout period between each period.
Participants by arm
| Arm | Count |
|---|---|
| Part A Participants received single 0.2 U/kg of body weight SC bolus injection of 100 U/mL LY900014 or Humalog. | 42 |
| Part B Participants received single 0.2 U/kg of body weight subcutaneous (SC) bolus infusion of either 100 U/mL LY900014 or Humalog delivered using the CSII pump. | 14 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 1-Part A First Intervention Day 1 | Withdrawal by Subject | 0 | 1 | 0 | 0 |
| Period 1-Part B First Intervention Day 1 | Physician Decision | 0 | 0 | 0 | 1 |
| Period 1-Part B First Intervention Day 1 | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Part A | Part B | Total |
|---|---|---|---|
| Age, Continuous | 20.5 Years STANDARD_DEVIATION 15.1 | 23.2 Years STANDARD_DEVIATION 11.1 | 21.2 Years STANDARD_DEVIATION 14.2 |
| Age, Customized Adolescents (12-17 years) | 14 Participants | 2 Participants | 16 Participants |
| Age, Customized Adults (18-64 years) | 15 Participants | 9 Participants | 24 Participants |
| Age, Customized Children (2-11 Years) | 13 Participants | 3 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants | 14 Participants | 54 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 | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 1 Participants | 4 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 | 37 Participants | 11 Participants | 48 Participants |
| Region of Enrollment Canada | 28 Participants | 10 Participants | 38 Participants |
| Region of Enrollment Germany | 14 Participants | 4 Participants | 18 Participants |
| Sex: Female, Male Female | 20 Participants | 8 Participants | 28 Participants |
| Sex: Female, Male Male | 22 Participants | 6 Participants | 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 | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 13 | 0 / 14 | 0 / 14 | 0 / 14 | 0 / 15 | 0 / 12 | 0 / 12 | 0 / 13 | 0 / 13 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 4 / 13 | 4 / 13 | 6 / 14 | 3 / 14 | 2 / 14 | 2 / 15 | 6 / 12 | 4 / 12 | 3 / 13 | 1 / 13 | 3 / 12 | 2 / 12 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 | 1 / 14 | 0 / 14 | 0 / 14 | 0 / 15 | 0 / 12 | 0 / 12 | 0 / 13 | 0 / 13 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve (AUC) Following Each Treatment Arm for Each Study Part
Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve (AUC(0 -7h)) following Each Treatment Arm for Each Study Part.
Time frame: Predose, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 90, 120, 150, 180, 240, 300, 360, and 420 minutes postdose
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Children-LY900014-Part A | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve (AUC) Following Each Treatment Arm for Each Study Part | 755 Picomoles*hour/Liter (pmol*h/L) | Geometric Coefficient of Variation 15 |
| Children-Humalog-Part A | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve (AUC) Following Each Treatment Arm for Each Study Part | 754 Picomoles*hour/Liter (pmol*h/L) | Geometric Coefficient of Variation 17 |
| Adolescents-LY900014-Part A | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve (AUC) Following Each Treatment Arm for Each Study Part | 962 Picomoles*hour/Liter (pmol*h/L) | Geometric Coefficient of Variation 17 |
| Adolescents-Humalog-Part A | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve (AUC) Following Each Treatment Arm for Each Study Part | 908 Picomoles*hour/Liter (pmol*h/L) | Geometric Coefficient of Variation 21 |
| Adults-LY900014-Part A | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve (AUC) Following Each Treatment Arm for Each Study Part | 987 Picomoles*hour/Liter (pmol*h/L) | Geometric Coefficient of Variation 20 |
| Adults-Humalog-Part A | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve (AUC) Following Each Treatment Arm for Each Study Part | 975 Picomoles*hour/Liter (pmol*h/L) | Geometric Coefficient of Variation 21 |
| Children-LY900014-Part B | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve (AUC) Following Each Treatment Arm for Each Study Part | 743 Picomoles*hour/Liter (pmol*h/L) | Geometric Coefficient of Variation 17 |
| Children-Humalog-Part B | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve (AUC) Following Each Treatment Arm for Each Study Part | 714 Picomoles*hour/Liter (pmol*h/L) | Geometric Coefficient of Variation 17 |
| Adolescents-LY900014-Part B | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve (AUC) Following Each Treatment Arm for Each Study Part | 842 Picomoles*hour/Liter (pmol*h/L) | Geometric Coefficient of Variation 20 |
| Adolescents-Humalog-Part B | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve (AUC) Following Each Treatment Arm for Each Study Part | 866 Picomoles*hour/Liter (pmol*h/L) | Geometric Coefficient of Variation 16 |
| Adults-LY900014-Part B | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve (AUC) Following Each Treatment Arm for Each Study Part | 1100 Picomoles*hour/Liter (pmol*h/L) | Geometric Coefficient of Variation 35 |
| Adults-Humalog-Part B | Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve (AUC) Following Each Treatment Arm for Each Study Part | 1070 Picomoles*hour/Liter (pmol*h/L) | Geometric Coefficient of Variation 35 |
p-value: 0.981395% CI: [0.918, 1.09]Mixed Models Analysis
p-value: 0.163895% CI: [0.976, 1.15]Mixed Models Analysis
p-value: 0.762395% CI: [0.933, 1.1]Mixed Models Analysis
p-value: 0.295295% CI: [0.962, 1.13]Mixed Models Analysis
p-value: 0.405295% CI: [0.901, 1.04]Mixed Models Analysis
p-value: 0.531495% CI: [0.948, 1.11]Mixed Models Analysis
Secondary
Glucodynamics (GD): Area Under the Baseline Subtracted Glucose Concentration Versus Time Curve Following Each Treatment Arm for Each Study Part
Glucodynamics (GD): Area Under the Baseline Subtracted Glucose Concentration Versus Time Curve (BG∆AUC(0-5h)) Following Each Treatment Arm for Each Study Part.
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 received at least one dose of study drug and had evaluable Glucodynamics data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Children-LY900014-Part A | Glucodynamics (GD): Area Under the Baseline Subtracted Glucose Concentration Versus Time Curve Following Each Treatment Arm for Each Study Part | 384 milligrams*hour per deciliter (mg*h/dL) | Standard Deviation 335 |
| Children-Humalog-Part A | Glucodynamics (GD): Area Under the Baseline Subtracted Glucose Concentration Versus Time Curve Following Each Treatment Arm for Each Study Part | 492 milligrams*hour per deciliter (mg*h/dL) | Standard Deviation 270 |
| Adolescents-LY900014-Part A | Glucodynamics (GD): Area Under the Baseline Subtracted Glucose Concentration Versus Time Curve Following Each Treatment Arm for Each Study Part | 577 milligrams*hour per deciliter (mg*h/dL) | Standard Deviation 247 |
| Adolescents-Humalog-Part A | Glucodynamics (GD): Area Under the Baseline Subtracted Glucose Concentration Versus Time Curve Following Each Treatment Arm for Each Study Part | 651 milligrams*hour per deciliter (mg*h/dL) | Standard Deviation 238 |
| Adults-LY900014-Part A | Glucodynamics (GD): Area Under the Baseline Subtracted Glucose Concentration Versus Time Curve Following Each Treatment Arm for Each Study Part | 372 milligrams*hour per deciliter (mg*h/dL) | Standard Deviation 179 |
| Adults-Humalog-Part A | Glucodynamics (GD): Area Under the Baseline Subtracted Glucose Concentration Versus Time Curve Following Each Treatment Arm for Each Study Part | 351 milligrams*hour per deciliter (mg*h/dL) | Standard Deviation 240 |
| Children-LY900014-Part B | Glucodynamics (GD): Area Under the Baseline Subtracted Glucose Concentration Versus Time Curve Following Each Treatment Arm for Each Study Part | 602 milligrams*hour per deciliter (mg*h/dL) | Standard Deviation 221 |
| Children-Humalog-Part B | Glucodynamics (GD): Area Under the Baseline Subtracted Glucose Concentration Versus Time Curve Following Each Treatment Arm for Each Study Part | 582 milligrams*hour per deciliter (mg*h/dL) | Standard Deviation 254 |
| Adolescents-LY900014-Part B | Glucodynamics (GD): Area Under the Baseline Subtracted Glucose Concentration Versus Time Curve Following Each Treatment Arm for Each Study Part | 614 milligrams*hour per deciliter (mg*h/dL) | Standard Deviation 160 |
| Adolescents-Humalog-Part B | Glucodynamics (GD): Area Under the Baseline Subtracted Glucose Concentration Versus Time Curve Following Each Treatment Arm for Each Study Part | 614 milligrams*hour per deciliter (mg*h/dL) | Standard Deviation 163 |
| Adults-LY900014-Part B | Glucodynamics (GD): Area Under the Baseline Subtracted Glucose Concentration Versus Time Curve Following Each Treatment Arm for Each Study Part | 343 milligrams*hour per deciliter (mg*h/dL) | Standard Deviation 194 |
| Adults-Humalog-Part B | Glucodynamics (GD): Area Under the Baseline Subtracted Glucose Concentration Versus Time Curve Following Each Treatment Arm for Each Study Part | 401 milligrams*hour per deciliter (mg*h/dL) | Standard Deviation 235 |